Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

ESA two revision > MoD > Flashcards

MoD Flashcards

1
Q

Define neoplasm

A

Abnormal growth of cells that persists after inital stimulus is removed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Define a malignant neoplasm

A

Abnormal growth of cells that persists after initial stimulus is removed and invades surrounding tissue with potential to spread to distal sites

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Define a tumour

A

Clinically detectible lump or swelling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Define cancer

A

Any malignant neoplasm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Define metastasis

A

malignant neoplasm spread from its original site to a non contiguous site

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Define dysplasia

A

Preneoplastic alteration - cells show disordered tissue organization but the alteration is reversible. It is usually seen in epithelia and can antedate appearance of cancer. There is a loss of uniformitiy of individual cells as well as architectural organization

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Which neoplasms show the ability to metastase?

A

Malignant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe bengin tumours

A

Grow in confined local area and have pushing outer margin- fibrous capsule that enables surgical excision

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe malignant tumours

A

Irregular outer margin and shape - they can show areas of ulceration and necrosis - may get loss of function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe how well cells are differentiated in benign and malignant tumours

A

bengin - well differentiated

malignant - vary from well to poorly differentiated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Define anaplastic

A

No ressemblance to any tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Give some features of worsening differentiation

A

Cells have increased nuclear size, nuclear:cytoplasmic ratio, increased nuclear staining, increased mitotic figures, and increased variation in size and shape of nuclei - pleomorphism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What indicates differentiation?

A

Grade - high grade poor differentiation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How are neoplasms caused ( briefly)

A

Accumulated mutations in somatic cells caused by inhibitors which are mutagenic agents and promoters that cause cell proliferation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the main intiators?

A

Chemicals, infection and radiation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe what monoclonal is and how this relates to neoplasm

A

All originate from a single cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Describe the study that worked out that neoplasms were monoclonal

A

From G-6-P dehydrogenase where there are several isoenzymes. In heterozygous women early in embyrogenesis one allele is randomly inactivated in each cell. 1 allele is heat stable and the other is heat labile - normal tissue is a patchwork but neoplasmic tissue only expresses one enzyme

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Genetic alterations leading to neoplasm affect what genes?

A

Proto oncogenes - oncogenes that become abnormally activated to favour neoplasm formation
Tumour supressor genes - normal supress neoplasm formation become inactivated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How are neoplasms named?

A

Site of origin
bengin of malignant
type of tissue formed
gross morphology - cyst or papiloma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What does a benign neoplasm end in?

A

Oma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What does a maligant epithlial neoplasm end in?

A

Carcinoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What does a maligant stromal neoplasm end in?

A

Sarcoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What does it mean if a malignant neoplasm is in situ or invasive ?

A

In situ- no invasion through the basement membrane

Invasive - through basement membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is a leukaemia ?

A

Malignant neoplasm of blood forming cells arising in bone marrow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What is a lymphoma?

A

Malignant neoplasm of lymphocytes - lymph nodes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What is a myeloma ?

A

Malignat neoplasm of plasma cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What are germ cell neoplasms?

A

Arise from pluripotent cells in ovaries or testes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What are neuroendocrine neoplasms ?

A

Cells distrubuted throughout the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What are blastomas?

A

Occur mainly in children formed form immmature precursor cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What is an adenoma ?

A

Benign epithlial neoplasm that forms in glandualar patterns and tumour derived from glands

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What is a papilloma?

A

Benign epithlial neoplasm producing macro or microscopic finger like projections from epithelial surface

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What is a squamous cell carcinoma ?

A

Carcinoma producing recognisable squamous cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What is a leiomyoma?

A

Benign tumour of smooth muscle cells eg in the uterus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What is a lipoma?

A

Benign tumour of fatty tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What is a sarcoma ?

A

Malignant tumour arising from mesencymal tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What is a leiomysarcoma ?

A

Malignant tumour of smooth muscle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What is a glioma?

A

Primary brain tumour that originates from the supportive cells of the brain including astrocytoma, oligodendroglioma and ependymoma.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What is a seminoma?

A

Malignant neoplasm of testicular epithelia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What is an embyronic carcinoma?

A

Characterised by primative epithelial cells with marked pleomorphism and various histological patterns - often part of mixed germ cell tumour

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What is a teratoma ?

A

Neoplasm arising from totipotent eclls - has tissue or organ components resembling normal derivatives of all three layers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What does the ability of malignant cells to invade and spread to distant sites lead to ?

A

Increased tumour burden

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What must a neoplasm be able to do to produce secondary sites??

A

Grow and invade at site one
Enter a transport system and lodge at secondary site
Grow at secondary site to form a new tumour

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

During the production of a secondary tumour what must neoplastic cells be able to do?

A

Avoid destruction by immune cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

What transport systems might neoplastic cells invade ?

A

Blood via capillaries and venules
lymphatic vessels
fluid in body cavities - transcoelmic spread

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

During the production of a secondary tumour what stage is the neoplasmic cells likely to fail at?

A

Colonisation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

What does invasion involve? What does this cause?

A

3 alterations
> altered adhesion
> stromal proteolysis
> motillity

Causes carcinoma cell phenotype that appears more like mesenchyme

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

How is altered adhesion brought about ?

A

Decrease in E-cadherin expression ( between malignant cells) and changes in integrin expression (between malignant cells and stromal proteins )

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Explain proteolysis when invading to form a secondary tumour?

A

Cells must degrade basement membrane and stroma to invade - proteases including matrix metalloproteinases.F

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

How do malignant cells take advantage of non neoplastic cells?

A

Formation of a cancer niche to provide growth factors and proteases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Altered motility causes what?

A

Changes in actin cytoskeleton

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

What causes a relapse?

A

Micrometastases starting to grow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

What determines the site of secondary tumour?

A

Regional drainage
Seed and soil phenomenon - explains unpredictable distrubution of blood borne metastases interaction between malignant cells and local tumour enviroment at secondary site

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

What are the most common secondary tumour sites?

A

Lung
bone
brain
liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

What are the local effects of neoplasm?

A

Direct invasion and destruction of normal tissue
ulceration at surface leading to bleeding
compression of adjacent structures
blocking of tubes and orifices or rupture and infarct

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

What are the systemic effects of neoplasm?

A

Increased tumour burden- parasitic effect on host
Together with secreted factors cause decrease in appetite , weight loss, malaise, immunosupressent and thrombosis
Benign neoplasm of endocrine glands produce hormones - malignant tumours cause release of PTHrP
neuropathies - brain and peripheral nerves affected
Skin problems, abnormal pigmentation , fever, clubbing and myositis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

Describe the alterations in growth control

A

Increased proliferation- self sufficiency in growth signals and insensitivity to inhibitory signals
Decreased cell death
Increased life span - telomerase activity
Altered growth factor / hormone and receptor
altered cell to cell interactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

What is a fibroma?

A

benign tumour of fibroblastic cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

What is a chondroma?

A

Bengin tumour of cartilaginous cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

What is a osteoma?

A

Bengin tumour of osteoblasts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

What is a cystadeonoma?

A

Benign epithelial neoplasm that forms large cystic masses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

What is a fibrosarcoma?

A

Malignant tumour that arises from fibroblasts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

What is a liposarcoma?

A

Malignat tumour of fatty tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

What is a rhabdomyosarcoma?

A

Malignant tumour of straited muscle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

What is a mesothelioma?

A

Malignant neoplasm of mesothelium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

What is a basal cell carcinoma?

A

Skin cancer derived from and perserving from basal cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

What is a hydatidiform mole ?

A

avascular or polycystic benign placental mass - occurs when extra set of paternal chromosomes in fertilised egg.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

What is a hamartoma?

A

Mass of disorgansed by mature specialised cells or tissue indignous to particular sites resulting from observant differentiation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

Describe the process of invasion

A

Process of infiltration and active destruction of surrounding tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

How do benign tumours cause hypercalcaemia? What are the symptoms?

A

Primary parathyroid adenomas produce hyperparathyroidism by increasing parathyroidism , increased Ca and bone reabsorption. hypophophataemia, increased excretion of ca and phosphate in urine
Painful bones, renal stones, groans and moans

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

How doe malignant tumours cause hypercalcaemia ?

A

Ectopic secretion of PTHrP in paraneoplastic syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

What is paraneoplastic syndrome?

A

Disease or symptom that is a consequence of presence of cancer in the body but not due to local presence of cancer cells mediated by humoral factors excreted by tumour cells or by an immune response against the tumour

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

What malignancies are associated with humoral hypercalcaemia of malignancy?

A

Breast, lung, kidney, and ovary

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

How is anaemia caused in malignancy?

A

Iron deficiency due to chronic external haemorhagging
anaemic of chronic disease - due to cytokine production normal stored iron
myelophthisic anemia - destruction of bone marrow
Aplastic anaemia secondary to treatment
Megaloblastic anaemia secondary to folate acid antagonists
immunohaemolytic anaemia secondary to reaction to drugs / tumour

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

What is cachexia?

A

Severe weight loss and debility due to loss of muscle mass and fat

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

How is cachexia caused?

A

Increased expenditure of resting energy due to cytokine production
production of lipid and proteins mobilising factors
anaemia and decreased food intake

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

What does the size of a cells population depend upon?

A

Rate of proliferation, differentiation and death via apoptosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

How do cells signal to each other?

A

Hormones, local chemical mediators and direct contact

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

Which genes control normal cell proliferation and how ?

A

Proto-oncogenes controlled by chemical signals from micro enviroment causing stimulation or inhibition when signalling molecules bind to receptor modulation of gene expression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

Name some growth factors

A

EGF VEGF PDGF and GCSF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

What are growth factors ?

A

Local mediators involved in cell proliferation- polypeptides act on cell surface receptors that are code for by proto-oncogenes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

How do growth factors work?

A

Bind to specific receptors stimulating transcription of genes that regulate entry into the cell cycle and passage through it
Increase growth by decreasing the time taken for cell cycle and conversion of quiescent cells to proliferating cells by making them enter the cell cycle.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

What do growth factors effect?

A

Cell proliferation/ inhibition, locomotion, contractibility, differentiation, viability, activation and angiogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

Where are the key check points in the cell cycle? Where and what is the R point?

A

End of G2

End of G1 - R point ( point of no return)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

What happens if a check point in the cell cycle is activated?

A

Delay the cell cycle and triggers DNA repair mechanisms or apoptosis by p53.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

How is the cell cycle controlled ?

A

Cyclins ( proteins) and CDK ( enzymes ) at G1/S transition. CDKs become activated by binding to and complexing with cyclins leading to phosphorylation and driving the cell cycle eg retinoblastoma susceptible proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

How is the activity of cyclins and CDKs regulated?

A

Tightly by cyclin inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

Describe permenant tissue in terms of their ability to regenerate ?

A

Stem cells present but not enough to mount an effective proliferation response to significant damage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

How are neurones replaced?

A

Glial cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
89
Q

Describe stable cells in terms of ability to regenerate

A

Stem cells normally quiscent or proliferate at a v. slow rate but proliferate persistently when required

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
90
Q

Describe labile cells in terms of ability to regenerate

A

Stem cells divide persistantly to replace losses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
91
Q

What is meant by the CNS shows plasticity

A

Lost neurones cannot be replaced - severed axons do not grow back after stroke but CNS able to establish alternative pathways

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
92
Q

Define regeneration

A

cells multiply to replace losses with identical cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
93
Q

Defin hyperplasia

A

Cells increase in number

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
94
Q

Define hypertrophy

A

Cells increase in size

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
95
Q

Define atrophy

A

Cells decrease in size

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
96
Q

Define metaplasia

A

Cells replaced by different type of cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
97
Q

Describe regeneration

A

Induced by growth factors, cell - cell communication and electrical/ nerve stimuli.
Usually as good as new but not always and not immediately- can be beneficial as influenza virus cannot attack regenerating ells
Maximum number of tissues dependent on lifespan - telomere shortening

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
98
Q

What is reconsitution ?

A

Replacement of a lost body part- coordinated regeneration of several types of cell
RARE cannot do a nail or a sweat gland

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
99
Q

Describe hyperplasia

A

Remains under physiological control and is reversible - increased functional demand or external stimuli.
Can occur secondary to pathological cause - proliferation normal response to abnormal condition
Repeated cell division expose cell to risk of mutation and neoplasm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
100
Q

Give a physiological hyperplasia

A

Proliferating endometrium in response to oestrogen, increased bone marrow production of RBCs in response to decreased O2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
101
Q

Give some pathological hyperplasia

A

Eczema, psorasis , and goitre formation in iodine deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
102
Q

Describe hypertrophy

A

Increased functional demand or hormonal stimulus leading to increased structural components so the workforce is shared over greater mass.
On removal of stimuli cells back to normal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
103
Q

Give some examples of physioloigcal hypertrophy

A

Skeletal muscle and pregnant uterus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
104
Q

Give some pathological hypertrophy examples

A

Ventricular hypertrophy in response to hypertension or valvular disease
Smooth muscle hypertrophy above intestinal stenosis
Bladder smooth muscle hypertrophy with some bladder obstruction in response to enlarged prostate gland

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
105
Q

Which organ may hypertrophy pathologically or physiologically ?

A

Cardiac muscle - exercise heart only under strain for short time frames, capillary beds also hypertrophy but not to same extent meaning in pathological heart relatively anoxia leading to increased chance of MI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
106
Q

Describe atrophy

A

Decreased structural components and function in response to decreased fuel or growth factors
Organ atrophy -combination of cellular atrophy and increased apoptosis - parenchymal cells disappear before stromal cells leaving lots of connective tissue.
Associated with age

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
107
Q

What may be seen under a microscope when looking at atrophied tissue

A

Residual bodies in cells - autophagosomes

Extracellular matrix can be lost - osteoporosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
108
Q

Give a physiological atrophy

A

Ovarian atrophy post menopause

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
109
Q

Give the causes of pathological atrophy and an example of each

A

Decreased functional demand - atrophy of disease - muscles
Loss of innervation - denervation atrophy- hand muscles after median nerve disease
Inadequate blood supply- thinning of skin on legs with peripheral vascular disease
Inadequate nutrition -muscles
Loss of endocrine stimulation - breast and reproductive organs
Persistant injury- polyomyostis
Aging - senile atrophy - brain and heart
Pressure - tissue around enlarging benign tumour
Thoracic aortic anyuerism - erodes throrax
Occulsion of secretory duct
Toxic agent and drugs
X-ray by direct cellular damage and microcirculatory damage
Immunological mechanism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
110
Q

Describe metaplasia

A

Abnormal regneration - altered stem cell differentiation - may represent an adaptive subsitiution of cells - sensitive to stress by cell type better able to withstand adverse enviroment
Some times prelude to dysplasia and cancer .
There is no metaplasia accross germ layers and only in cells that can replicate.
Change causes expression of a new genetic programme to occur secondary to signals from molecules such as cytokines and GF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
111
Q

Give some examples of metaplasia

A

Smoking - bronchial pseuostratified ciliated to stratified squamous epithelial
Barretts oesophagus - stratified squmaous to gastric glandular epithilium with persistent acid reflux
Bone marrow tissue destroyed- splenic tissue to bone marrow
Connective tissue to bone in skeletal muscle post injury

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
112
Q

Define hypoplasia

A

Under or incomplete development of tissue/ organ at embyronic stage - inadequate cell number eg kidneys, breast, testes and chamber of heart

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
113
Q

Define aplasia

A

Complete faillure of an organ to develop- embyronic development disorder

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
114
Q

Define involution

A

Normal programmed shrinkage of an organ eg uterus post child birth

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
115
Q

Define atresia

A

Congential imperforation of an openning

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
116
Q

Define atheroma

A

Accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
117
Q

Define atherosclerosis

A

Thickening and hardening of arterial walls as a consequence of atheroma.
Clinical effects include heart disease and stroke

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
118
Q

Define arteriosclerosis

A

Thickening of the walls of ateries and arterioles usually as a result of hypertension or diabetes mellitus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
119
Q

What are the macroscopic features of atheroma

A

Fatty streak - lipid deposits in the intima, yellow and slightly raised
Simple plaque - raised yellow/white, irregular outline, widely distrubuted and enlarged
Complicated plaque- thrombosis, haemorrhaging into plaque, calcification and aneuryism formation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
120
Q

What are the early microscopic features of atheroma?

A

Proliferation of smooth muscle, accumulation of foam cells and extracellular lipids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
121
Q

What are the later microscopic features of atheroma?

A

Fibrosis, necrosis, cholesterol clefts, and presence of inflammatory cells , disruption of internal elastic lamina , damage extends to media, ingrowth of blood vessels and plaque fissuring

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
122
Q

What are the complications of atheroma ?

A

Thrombosis, haemorrhaging into the plaque, calcification and aneuryism formation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
123
Q

What are the common sites of atheroma ?

A

Aorta, coronary arteries, carotid arteries, cerebral arteries, and leg arteries

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
124
Q

What are the clinical effects of ischaemic heart disease?

A

Sudden death, MI, angina pectoris, arrhymias , cardiac failure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
125
Q

What are the clinical effects of cerebral ischaemia?

A

Transient ischaemic attack, stroke and multi infarct dementia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
126
Q

What are the clinical effects of mesentric ischaemia ?

A

Ischaemic colitis, malabsorption and intestinal infarct

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
127
Q

What are the clinical consequences of peripheral vascular disease?

A

Intermittent claudication, leriche syndrome, ischaemic rest pain and gangrene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
128
Q

What is intermittent claudication?

A

Pain in calf due to poor perfusion of walking/exercise

As atheroma worsens pain comes on in decreasing distances

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
129
Q

What are the pathogenesis factors for the development of atheroma ?

A

Age - slowly increases throughout adult life
Gender - women protected before menopause
Hyperlipidaemia - high plasma cholesterol associated with atheroma (LDL most significant)
Smoking - powerful risk factor for IHD - risk falls when given up
Hypertension
Diabetes mellitus - doubles risk of IHD, protective effect in pre menopausal women lost
Alcohol- greater than five units a day
Infection - chlamydia pneumonia, helicobacter pylori, cytomegalovirus
Obesity
Soft water
Oral contraceptives
Genetics - variation in apolipoproteins
Stress and personality types

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
130
Q

Describe the thrombogenic thoery for development of atheroma

A

Plaque formed by repeated thrombi sticking to arterial walls then become associated with lipid which forms a cap over thrombus
Atheroma grows as process is repeated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
131
Q

Describe the insudation theory of development of atheroma

A

Endothelial injury leads to inflammation and increased permeability to lipid from plasma allowing lipids into vessel wall from plasma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
132
Q

Describe the monoclonal hypothesis for development of atheroma

A

Crucial role for smooth muscle cell proliferation- each plaque is monoclonal and might represent abnormal growth control - they are benign tumours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
133
Q

Describe the reaction of injury hypothesis for development of atheroma

A

Plaque forms in response to endothelial injury, hypercholesterolaemia leads to endothelial damage. Injury increases permeability and allows platelet adhesion and monocytes penetrate endothelium, smooth muscle cells proliferate and migrate.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
134
Q

Describe the unifying hypothesis

A

1) Endothelial injury due to raised LDL, toxin, hypertension and haemodynamic stress
2) causes platelet adhesion , PDGF release, SM proliferation and migration, insudation of lipid, LDL oxidation , uptake of lipid by SM and macrophages, migration of monocytes
3) stimulation of smooth muscle cells to produce matrix material
4) Foam cells secrete cytokines causing further SM cell stimualtion and recruitment of other inflammatory cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
135
Q

What is the function of endothelial cells in atherogenesis?

A

Haemostasis - altered permeability to lipoprotein, secretion of collagen and stimulation of proliferation and migration of SM cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
136
Q

What is the function of platelets in atherogenesis ?

A

Role in haemostasis and stimulation proliferation and migration of SM cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
137
Q

What is the function of smooth muscle cells in atherogenesis?

A

Take up LDLs and other lipids to become foam cells

Synthesise collagen and proteoglycans

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
138
Q

What is the function of macrophages in atherogenesis?

A

Oxidise LDLs, take up lipids to become foam cells, secrete protease modifying matrix, stimulate proliferation and migration of smooth muscle cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
139
Q

What is the function of lymphocytes in atherogenesis?

A

TNF may effect lipoprotein metabolism, stimulate proliferation and migration of smooth muscle cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
140
Q

What is the function of neutrophils?

A

Secrete proteases leading to continued damage and inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
141
Q

How can atheroma be prevented?

A 
No smoking
Reduce fat intake
Treat hypertension/ diabetes
Not too much alcohol
Aspirin
Lipid lowering drugs
Regular exercise and weigh control
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
142
Q

Describe the cellular events which lead to atheroma?

A

Endothelial damage leads to platelets which released PDGF and this causes smooth muscle proliferation. The smooth muscle cells take the lipid with it into the intima from the media and macrophages arrive and phagocytose fat becoming foam cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
143
Q

Define haemostasis

A

Arrest of bleeding either by physiological properties of vasoconstriction and coagulation or by surgical means.
It represents a balance between procoagulant and anticoagulant forces.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
144
Q

What does successful haemostasis depend on?

A

Vessel wall - constrict to limit blood loss

Platelets - adhere to damage vessel wall and each other to form a platelet plug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
145
Q

What is the platelet release reaction?

A

ATP hydrolysed causing platelet aggregation
Platelet factor 3 and 5HT important in coagulation
Von willebrand factor release is also prothrombotic
Platelets coalesce after aggregation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
146
Q

Describe the major features of the coagulation system

A

Cascade - series of inactive components converted to active components, mostly synthesized in the liver and needs vitamin K
Prothrombin to thrombin leading to conversion of fibrinogen to fibrin
Tight regulation is needed as lots of amplification at each stage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
147
Q

What is the fibrinolytic system?

A

Break down of fibrin- plasminogen to plasmin with activator
Streptokinase and tPA
CLOT BUSTERS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
148
Q

Define a thrombus

A

Formation of a solid mass from the constituents of blood within the circulatory system during life

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
149
Q

What are the three fundamental predisposing factors to thrombosis? What do they make up?

A

Abnormalities in blood flow - stagnation and turbulence
Abnormalities of the vessel wall - atheroma, direct injury and inflammation
Abnormalities of the constituents of blood - smokers, post op, post partum
Known as VIRCHOW’S TRIAD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
150
Q

Give the appearance of a arterial thrombi

A

Pale, granular, lines of Zahn, low cell count

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
151
Q

Give the appearance of a venous thrombi

A

Soft, gelatinous, deep red, higher cell count

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
152
Q

What are the outcomes of thrombosis?

A

1) lysis - dissolution of thrombus, fibrinolytic system active, blood flow is re-established
2) propagation - progressive spread of thrombosis - distally in arteries and proximal in veins
3) organisation - reparative process - ingrowth of fibroblast and capillaries - lumen remains obstructed
4) Recanalisation - blood flow established but usually incomplete , one or more channel formed from organising thrombus
5) Embolism - part of the thrombus breaks off , travels through blood stream and lodges at distant site

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
153
Q

What are the effects of a venous thrombus?

A

Congestion, oedema , ischaemia and infarction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
154
Q

What are the effects of a arterial thrombus?

A

Ischaemia, infarction, depends on site and collateral circulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
155
Q

Define an embolism

A

Blockage of a blood vessel by a solid, liquid or gas at a site distant from its origin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
156
Q

Other than a thrombus what can cause an embolism?

A

Air, amniotic fluid, nitrogen, medical equipment and tumour cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
157
Q

What are some of the predisposing factors form DVTs?

A

Immobility, post op, pregnancy and post partum, oral contraceptive pill , severe burns, cardiac failure and disseminated cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
158
Q

What treatment is there fore DVTs?

A

Better to identify people at risk and treat prophylaxily

Intravenous heparin/ oral warfarin and leg compression during surgery

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
159
Q

When is a PE fatal?

A

> 60% reduction in blood flow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
160
Q

What do recurrent minor PEs lead to ?

A

Pulmonary hypertension

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
161
Q

What causes a fat embolism?

A

Post fracture leakage from bone marrow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
162
Q

Describe haemophilia

A

X linked recessive
A - problem with factor 8
B- problem with factor 9
Features - excessive bleeding , easy bruising , haemartritis
Lab findings - normal PT, increased PTT, Prolonged APTT
Treatment - prevent bleeding , manage injuries. watch meds that may thin blood, infusion of missing factor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
163
Q

What is disseminated intravascualr coagulation?

A

Generalised activation of platelets and coagulation cascade causes formation of thromboembolism in distal blood vessels which uses up all clotting factors and platelets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
164
Q

What are the consequences of disseminated intravascular coagulation?

A

Spontaneous bleeding, bleeding at sites of thrombosis, ischaemia of most organs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
165
Q

What are the causes of disseminated intravascular coagulation?

A

Systemic disease, major trauma, chemotherapy, septicemia, snake bite, obstetric complications

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
166
Q

What is the treatment for disseminated intravascular coagulation?

A

Plasma transfusion of clotting factors, heparin to prevent clotting

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
167
Q

What is thrombocytopenia?

A

Low platelet count due to defficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
168
Q

What are the causes of thromboytopenia?

A

Decreased production- aplastic anaemia due to cancer , B12 deficency, chemotherapy , cytotoxic production
Dilution - after large transfusion
Sequestered - due to large spleen which reduces number in circulation
Increased destruction - idiopathic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
169
Q

What are the test results for thrombocytopenia?

A

Normal PT and PTT
Decreased platelet count
prolonged bleeding time

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
170
Q

What are the treatments for thrombocytopenia?

A

Glucocorticoids/ immunoglobulin to treat abnormal immune reaction, platelet transfusion and splenectomy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
171
Q

What is thrombophilia?

A

Blood has increased tendancy to clot

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
172
Q

What types of thrombophilia are there?

A

Factor V leiden - caused by gene mutation
Prothrombin 20210 mutation - excessive prothrombin leads to more clots
Anti thrombin deficiency - lack of natural anticoagulants
Antiphospholipid syndrome - automimmune destruction of lipids by antibodies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
173
Q

What are the symptoms of thrombophilia?

A

Increased risk of DVT and pulmonary embolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
174
Q

How do you diagnose thrombophilia?

A

Blood test to look for anticoagulant deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
175
Q

What are the treatments for thrombophilia?

A

Anticoagulants
loose weight
avoid risk factors for DVT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
176
Q

What happens during chronic inflammation?

A

Process of healing with production of granulation tissue occur simultaneously

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
177
Q

What is the dominant cell in chronic inflammation?

A

Macrophage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
178
Q

What might the injurious agent be in chronic inflammation?

A

Micro organism, sterile but irritating substance, foreign body, crystaline substance or antigen overlapping with host immune system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
179
Q

How does chronic inflammation arise?

A

After or alongside acute inflammation
Chronic persisant infections
Autoimmune conditions
Prolonged exposure to toxic agents

180
Q

What is the function of the macrophage during chronic inflammation?

A

Products eliminate injurious agent and initiate repair, breakdown extracellular matrix, cause fibroblast proliferation, collagen deposition and angiogenesis.
Responsible for most of the tissue damage, attract neutrophils and lymphocytes, display antigens, stimulate T cell response and phagocytose.

181
Q

What is the function of the lymphocytes in chronic inflammation?

A

Processing antigens, secreting antibodies, secreting cytokines, killing cells - natural killer cells

182
Q

What is the function of eosinophils in chronic? inflammation?

A

Parasite infection, allergic reaction and immune response

183
Q

What is the function of fibroblasts and myofibroblasts in chronic inflammation?

A

Produce - collagen, elastin and glucosaminoglycans, differentiate into myofibroblasts that can contract drawing wound edges together

184
Q

What are giant cells ? What type of inflammation are they seen in?

A

Activated macrophages fuse with each other to form one cell due to fustrated phagocytosis. Granulomatous inflammation

185
Q

What are the types of giant cells?

A

Langhans - seen in TB nuclei around the periphery
Toutans - form lesions where high lipid content, contain foam cells - nuceli arranged in a circle towards the center
Foreign body - hard to digest foreign body present - nuclei random

186
Q

What are the effects of chronic inflammaion?

A 
Impaired function
Excessive fibrous tissue as fibroblasts produce more collagen than is necessary
Atrophy
Tissue destruction
Carcinoma 
Resolution
187
Q

Define granuloma

A

Focus of chronic inflammation consisting of microscopic aggregation of macrophages that are transformed into epithelial like cells surrounded by a collar of mononuclear leukocytes.

188
Q

What are granulomas used for?

A

Method of dealing with particles that is poorly soluble or difficult to eliminate

189
Q

What types of granulomas can be seen?

A

Foreign body granulomas - macrophages, foreign body giant cell, epitheloid cell , fibroblast and few lymphocytes
Hypersensitivity or immune type granulomas - develop around insoluble but antigenic particle cause cell mediated immunity

190
Q

In what diseases are granulomas seen?

A

Sarcoidosis, crohns, wegners , tb (caseous necrosis in the middle)

191
Q

Describe rheumatoid arthritis

A

Inflammation of the joints due to an autoimmune disease which produces antibodies that attack the synovium damaging the cartilage, bone and joint itself.
Increased lymphocytes, macrophages and plasma cells.
May develop rheumatoid nodules of granuloma on the forearm which contains fibrin, many macrophages and lymphocytes

192
Q

Describe ulcerative colitis

A

Whole colon inflammation resulting in ulcerated colon, distorted crypt architecture ( loss of goblet cells), granulated cytoplasm. Superficial disease which leads to bleeding and diahorrea.
Increased risk of bowel cancer

193
Q

What are some of the complications of ulcerative colitis?

A

Cholecystitis - inflammation of the gall bladder
Enteropathic arthritis - peripheral and axial
Erythrosis of the skin - red painful lumps on the skin and muscous membrane from inflammation of fat
Piodema gangrensoa - necrotic tissue of the legs, initally caused by deep ulcers which begin as small bug bites
Episcleritis
Iritis
Hepatitis and cirrhosis
Primary sclerosing cholangitis - inflammation and blockage of bile ducks leading to prevention of flow of bile leading to cirrhosis of the liver

194
Q

Describe crohns disease

A

Whole of the GI tract in a discontinous distrubution presenting with granulomas, transmural presentation, fibrosis and less crypt abscess than UC

195
Q

Describe chronic cholescystis

A

Repeated obstruction of the gall bladder with gallstones meaning acute inflammation leads to chronic inflammation and fibrosis of the gall bladder wall. Can be treated surgically by removal of the gall bladder.
Gall bladder will appear thick and white on the surface due to an excessive fibrosis coating

196
Q

Describe chronic gastritis

A

Chronic inflammation of the gastric muscosa- inflammation mainly consists of lymphocytes. caused by helicobacter pylori. increased acid secretion

197
Q

What is sarcoidosis ?

A

Chronic disease affecting multiple systems in the body- build up of macrophages into granulomas. May be foreign body giant cells present and non caseating and immune type granulomas in lungs

198
Q

Describe TB

A

Fever, night sweats , haemotypsis pleuritic pain
Caused by mycobacteria and produces no toxins or lytic enzymes. Causes disease by perisistence and induction of cell mediated immunitiy
outcomes include - fibrosis and scarring, granuloma formation in the lung, erosion into the bronchus, tuberculous emphysema and erosion into blood stream

199
Q

How can you tell the difference between TB and sarcodosis ?

A 
TB - caseous necrosis 
Acid fast stain
bacterial culture
PCR for microbacterial DNA
ACE test
Serum calcuim blood test
200
Q

Define an ulcer

A

Breach in the mucosa to level of submucosa or deeper

201
Q

What are the three processes involved in healing?

A

Haemostasis, inflammation and regeneration

202
Q

Define regeneration

A

replacement of dead tissue by functional differentiated cells from stem cells essential for restoration of function and appearance. It requires an intact connective tissue scaffold

203
Q

What are labile tissue ? Give their properties and some examples of them

A

Continous dividing tissue - proliferate throughout life replacing cells that are destroyed.
Eg surface epithelia, lining mucosa of secretory ducts of the glands of the body, columnar epithelia of the GI and uterus, bladder epithelia , cells of bone marrow and haematopoietic tissue

204
Q

What are stable tissue ? Give their properties and some examples of them

A

Quiscent tissue - low level of replication but can undergo rapid division in response to stimuli and can renconstruct tissue of origin
Eg Parenchymal cells of liver, kidney, and pancreas, fibroblasts, smooth muscle cells , endothelial cells, resting lymphocytes and other white blood cells

205
Q

What are permenant tissue ? Give their properties and some examples of them

A

cells have left the cell cycle and cant undergo mitotic division- no or only a few stem cells that can be recruited to replace - cannot mount an effective proliferative response to significant cell loss
Eg neurones, skeletal and cardiac cells

206
Q

What is the function of stem cells?

A

Internal repair system to replace lost or damaged cells in tissue

207
Q

What sort of division do stem cells show ? Explain

A

Asymetrical replication
1 cell produced remains as a stem cell
1 cell produced differentiates into a mature non dividing cell

208
Q

What is a unipotent stem cell ?

A

Give rises to one type of adult cell- lineage specific

209
Q

What is a multipotent stem cell?

A

Can produce several types of differentiated cell eg haemopoeitic stem cell

210
Q

When does fibrous repair occur?

A

Framework is destroyed, on going chronic inflammation or necrosis of specialised paremchymal cells

211
Q

What processes are involved in fibrous repair?

A

Phagocytosis of necrotic tissue debris
proliferation of endothelial cells which result in small capillaries that grow into the area
Proliferation of fibroblasts and myofibroblasts that synthesise collagen and cause wound contraction
Granulation tissue become less vascualr and matures into fibrous scar
Scar matures and shrinks due to contraction of fibrils within myofibroblasts

212
Q

Describe fibrous repair?

A

1) inflammatory cells infiltrate - blood clot, acute inflammation around the edges, macrophages and lymphocytes migrate into clot
2) replaced by granulation tissue - BV and extracellular matrix
3) maturation - decrease cells increased collagen, myofibroblasts contract, vessels differentiate and decrease leading to fibrous scar

213
Q

What are the functions of the extracellular matrix

A 
supports cells 
Separates tissue compartments
Sequester growth factors
Communication between cells 
cell migration
214
Q

Give a few diseases that are due to defects in collagen

A

Scurvy
Ehlers danlos
Osteogenesis imperfecta
Alport syndrome- X linked disease abnormal IV collagen- progresses to renal failure, deafness and eye disorders

215
Q

Describe growth factors

A

Polypeptides that act on specific cell surface receptors- coded for by proto-oncogenes and can be considered local hormones as they only act over a short distance.

216
Q

Describe epidermal growth factor

A

Mitogenic for epithelial cells, heptocytes and fibroblasts
produced by keratinocytes. macrophages, and inflammatory cells
bind to epidermal growth factor receptors

217
Q

Describe vascular endothelial growth factor

A

Induces blood vessel development and role in growth of new blood vessels in tumours, chronic inflammation and wound healing

218
Q

Describe platelet derived growth factor

A

stores in platelets alpha granules, and released on platelet activation; also produced by macrophages enodthelial cells, smooth muscle cells and tumour cells
cause - migration and proliferation of fibroblast smooth muscle cells and monocytes

219
Q

Describe tumour necrosising factor

A

Induces fibroblast migration, fibroblast proliferation and collagenase secretion

220
Q

What is contact inhibition?

A

Normal cells will replicate until they have cells touching them and then will stop ie they form a monnolayer of cells with no overlap.

221
Q

What proteins help in contact inhibition?

A

Adhesion molecules ;
Cadherins - adhesion molecules that bind cells to each other
Integrins - bind cells to the extracellular matrix

222
Q

What are the two methods a scar can heal by?

A

Primary and secondary intention

223
Q

Describe healing by primary intention

A

Incised wound, apposed edges , minimal clot and granulation, non infected , disruption to basement membrane continutity but only a small number of cell deaths .

224
Q

Describe the process of healing by primary intention

A

Seconds to minutes – haemostasis. Severed arteries contract. The narrow space fills with clotted blood, there is dehydration of the surface clot and a scab is formed. Seconds to minutes -The scab seals off the wound from the environment and prevents bacteria entering .
• Minutes to hours – inflammation. Neutrophils appear at the margins of the incision. This wards off bacteria. Inflammation is triggered automatically. In a sterile wound the number of leucocytes is not enough for the fluid to be classified as pus.
• Up to 48 hours – migration of cells. Macrophages start to appear and begin to scavenge dead neutrophils. They become activated and secrete cytokines that attract other cells such as fibroblasts, and endothelial cells (capillary sprouts start to appear- vital for nutrients delivery – exploited by malignant cells). Spurs of basal epidermal cells at the edge of the cut creep over the denuded cells travelling at approximately 0.5mm/day. They deposit basement membrane components as they go. They fuse in the midline beneath the scab.
• Three days – regeneration. Macrophages replace neutrophils. Granulation tissue (fibroblasts and new capillaries) invades the space. Epithelial cell proliferation thickens the epidermal layer and epidermal cells undermine the scab which then falls off. Activated fibroblasts produce collagen. Angiogenesis progresses.
• Seven to ten days – early scarring. The wound is filled with granulation tissue. The fibroblasts proliferate and deposit collagen fibres which form a fibrous mass, i.e., a scar. The epidermis normalises and keratinises but skin appendages, e.g., hair and sweat glands, don’t form (this is why scars are hairless). White cell infiltrate, oedema and increased vascularity disappear. Regression of vascular channels.
• One month to two years – scar maturation. The scar is a mass of fibrous tissue with many collagen fibres, few cells and few vessels. It also has few elastic fibres and therefore little recoil (this is why scars tend to stretch). As capillaries disappear old scars appear white (new scars are pink).

225
Q

Describe the type of wounds that would heal by secondary intention

A

Infarct, ulcer, abscess, large wound, excisional wound ,wounds with tissue loss, separated edges

226
Q

Describe healing by secondary intention

A

In healing by secondary intention the open wound is filled by abundant granulation tissue which grows in from the wound margins. As there is a larger clot and more necrotic debris than in a wound with closely opposed edges, the inflammatory reaction is more intense. Considerable wound contraction must take place to close the defect. Initially this occurs as the scab contracts when it dries and shrinks. After about a week myofibroblasts appear and contract (myofibroblasts are fibroblasts that develop into a contractile phenotype, they resemble a smooth muscle cell and are intermediate between fibroblasts and smooth muscle cells). An open wound contracts as if its margins were being drawn into the centre – the final shape of the scar depends on the original shape of the wound. Substantial scar formation is seen in healing by secondary intention and the new epidermis is often thinner than is usual. Healing will be delayed if infection is present.

227
Q

Describe healing after a fracture

A

A fracture results in a haematoma which fills the gap and surrounds the bone injury.
• A fibrin mesh and then granulation tissue is formed. Platelets and inflammatory cells release cytokines. These activate osteoprogenitor cells to osteoclastic and osteoblastic activity. Necrotic tissue removed and capillaries develop.
• Soft callus (also called procallus or fibrocartilagenous callus) forms at about one week. It consists of fibrous tissue and cartilage within which woven bone begins to form. It usually extends beyond the volume occupied by the uninjured bone and forms a bulge around the fracture site.
• Hard callus (or bony callus) appears after several weeks. It is laid down by osteoblasts. The bone formed initially is woven bone. It is weaker as it is less organised than lamellar bone but it can form quickly.
• Formation of lamellar bone which is more organised and stronger than woven bone.
• Remodelling of the bone occurs in response to mechanical stresses placed on it. Bone not physically stressed is resorbed and the outline of the bone is re-established.

228
Q

Describe the local factors that can affect healing

A

• Size, location and type of wound - indicates if healing is by primary or secondary intention and if regeneration or scarring will occur
• Blood supply - e.g., arteriosclerosis impedes healing, areas with high vascularity (e.g., face) heal well
• Denervation – impairs healing
• Local infection – produces persistent tissue injury and inflammation
• Foreign bodies – produce persistent inflammation and favour infection
• Haematoma – if large and persistent can slow healing
• Necrotic tissue – needs clearing during the process of repair, therefore if a large amount is present healing can take longer
• Mechanical stress – can pull apart delicate tissue in the early stages of healing
• Protection (dressings) – help to keep the wound clean and free from infection
- surgical techniques - better reduce the healing time

229
Q

Describe the systemic effects that affect healing

A
  • Age – children heal quickly, elderly people more slowly
  • Anaemia, hypoxia and hypovolamia (e.g., following trauma) – poorer oxygen delivery to healing tissue
  • Obesity – can cause increased tension on wounds and wound dehiscence
  • Diabetes – microangiopathy impairs blood supply to damaged area. There is also a decreased resistance to infection
  • Malignancy – due to the cachexia (wasting of the body) seen with malignant tumours
  • Genetic disorders - e.g., Ehlers-Danlos syndrome
  • Drugs - steroids (inhibit collagen synthesis), cytotoxics (anti-mitogenic and impair cell proliferation and healing), antibiotics (treat bacterial infections, reduce inflammation and can speed up healing)
  • Vitamin deficiency - vitamin C deficiency inhibits collagen synthesis
  • Malnutrition – lack of essential substances such as amino acids for protein synthesis
  • Systemic infection
230
Q

What are some of the complications of fibrous repair?

A
  • Formation of fibrous adhesions (e.g., pleural adhesions) compromising organ function or blocking tubes
  • Loss of function due to replacement of specialised functional parenchymal cells by non-functioning collagenous scar tissue (e.g., healed myocardial infarction where the scar tissue in the heart doesn’t contract)
  • Disruption of complex tissue relationships within an organ, i.e., distortion of architecture interfering with normal function (e.g., as seen in liver cirrhosis)
  • Overproduction of fibrous scar tissue i.e., keloid scar. A keloid scar is an overgrowth of fibrous tissue, due to an overproduction of collagen, that exceeds the borders of the scar. They don’t regress and excision just creates another one. They are commoner in Afro-Caribbeans.
  • Excessive scar contraction causing obstruction of tubes, disfiguring scars following burns or joint contractures (fixed flexures). If very severe it can even impair blood circulation.
  • Insufficient fibrosis – diabetes elderly malnutrition and steroids
231
Q

Describe the healing capacity of the cardiac muscle and why this happens?

A

Very limited if any- permenant tissue

232
Q

Describe the healing capacity of the liver and why this happens?

A

Remarkable capacity - compensatory growth of liver tissue and restoration of mass by enlargement of the lobes that remain

233
Q

Describe the healing capacity of peripheral nerves and why this happens?

A

Proximal stumps of the degenerated axons sprout and elongate using schwann cells to guide them back to tissue - wallerian degeneration 1-3mm/day

234
Q

Describe the healing capacity of cartilage and why this happens?

A

Does not heal well as it lacks blood supply, lymphatics and innervation

235
Q

Describe the healing capacity of the central nervous system and why this happens?

A

Replaced with glial cells

236
Q

Describe the healing capacity of the skeletal muscle and why this happens?

A

some regenerative capacity through satellite cells - attached to endomysial sheaths - reversed pool of stem cells that can generate myocytes post injury

237
Q

What is accountable for the increased risk of cancer over the last century?

A

Increased lifespan

238
Q

What accounts for cancer risk?

A

Combination of intrinsic factors such as hereditary, age, gender and extrinsic factors related to environment and behaviours

239
Q

What are the five leading behavioural and lifestyle risks for cancer ? What proportional of cancers do these make up?

A 
High BMI
Low fruit and veg intake due to lack of fibre so increased transition time
Lack of physical activity 
Tobacco use
Alcohol use
make up about 30% of cancer deaths
240
Q

What proportion of cancer deaths are associated with tobacco smoke ?

A

1/4

241
Q

What proportion of a persons cancer risk is from extrinsic factors?

A

85%

242
Q

What are the three categories of extrinsic carcinogens?

A

Radiation
Chemicals
Infections

243
Q

What lessons about carcinogens can be demonstrated from chemical studies?

A

Large time delay between exposure and onset
Risk of neoplasm depends on dosage
Sometimes organ specificity

244
Q

Why is dosage of chemicals an important factor?

A

Enviromental levels such as second hand smoke and industrial carcinomas

245
Q

Describe 2-napthylamine

A

Industrial carcinogen that causes bladder carcinoma

246
Q

Which must come first promototer or initiator ? does it matter?

A

Initiator

247
Q

What does an initiator cause ?

A

mutatations

248
Q

What do promoters cause?

A

Proliferation

249
Q

What test shows the role of initiators and promoters?

A

Ames test

250
Q

What does the collective action of intitators and promoters cause? How does this become fully malignant?

A

monoclonal expansion of mutant cells

Through progression

251
Q

How can chemical carcinogens be classified?

A 
Polycyclic aromatic hydrocarbons
Aromatic Amines
N-Nitriso compounds
alkylating agents
Natural products
252
Q

What are pro-carcinogens? What effect does this have when testing to check if something is a carcinogen?

A

Chemicals that are only converted to carcinogens by the cytochrome P450 enzymes in the liver.
In the ames test you add liver to allow this process to take place

253
Q

What are completer carcinogens ? Give an example

A

Chemicals that are both initiators and promoters

Eg tobacco smoke

254
Q

What is radiation?

A

Any type of energy that travels through space

255
Q

Describe ionising radiation

A

Strips electrons from atoms

Including X-rays and nuclear radiation

256
Q

How deep can UV light penetrate? What is the consequence of this?

A

Can only penetrate the skin- skin cancer risk factor

257
Q

How can radiation dammage dna ?

A

Directly- breaks the molecules or alters bases

Indirectly - generation of free radicals through hydrolysis of water

258
Q

For most people what is their exposure to ionising radiation?

A

Background radiation from radon which seeps out from the earth’s core and medical tests

259
Q

How can infections act as carcinogens ?

A

Directly- affect genes that control cell growth
Indirectly- causing chronic tissue injury where regeneration acts as a promoter for exsiting mutations or causes new mutations from DNA replication errors

260
Q

Describe how HPV virus effects cervical carcinoma

A

Directly because it expresses E6 and E7 proteins that inhibit p53 ( allowing host DNA to intergrate and stop apoptosis) and pRB protein function.

261
Q

Describe how Hep B and C effects risk of liver cancer

A

Indirectly by causing liver cell injury and regeneration

262
Q

How does bacteria and parasite infections lead to increased risk of cancer?

A

Helicobacter pylori causes chronic gastritis inflammation and parasitic flukes cause inflammation in bile ducts and bladder mucosato increased risk of gastric , cholangio and bladder carcinomas

263
Q

How does HIV lead to an increased cancer risk?

A

Indirectly by lowering immunity and allowing other potientally carcinogenic infections to occur

264
Q

How can an inheritied predisposition to cancer occur? In what type of cancer was this shown?

A

Germline mutations - retinoblastoma

265
Q

What is the two hit hypothesis?

A

Explains the differences in familial inherited cancers and those that occur sporadically
Familial cancers - fist hit delivered through germ line affects all cells in the body
Second hit was a somatic mutuation - tending to occur in multiple cells
Sporadic reintoblastoma has no genetic mutation and so requires both hits to be somatic and to occur in the same cell

266
Q

Which genes inhibit neoplastic growth? What is the consequence when mutations occur to cause neoplasm?

A

Tumour surpressor genes - both alleles must be inactivated explaining the two hits hypothesis

267
Q

Which genes enhance neoplastic growth?

A

Oncogenes - abnormally activated version of proto-oncogenes - only one needs to be mutated to favour neoplastic growth

268
Q

What was the first oncogene to be discovered ? In what proportion of cancers is this mutated?

A

RAS

1/3

269
Q

What does the normal RAS gene do?

A

Codes for a small G protein that relays signals into the cell that eventually pushes the cell past the cell cycle restriction point Q

270
Q

What does a mutated RAS gene do ?

A

Produces a constant signal to pass through the cell cycle restriction point - inactivation of both allows unrestricted passage through the restriction point

271
Q

What can proto-oncogenes code for?

A 
Growth factors 
Growth factor receptors
Plasma membrane signal transducers
Intracellular kinases 
Transcription factors
Cell cycle regulators
Apoptosis regulators
272
Q

What is xerodermapigmentosum caused by?

A

Mutations in DNA repair genes that affects DNA excision repair

273
Q

What is hereditary non polyposis colon cancer caused by?

A

Dominant germline mutation that affects one of the several DNA mismatch repair genes

274
Q

What is familial breast cancer associated with?

A

BRCA 1 or BRCA 2 genes that are very important in repairing double strand DNA breaks

275
Q

What is genetic instability?

A

Accelerated mutation rate found in malignant neoplasms caused by mutations and chromosome segregation in mitosis

276
Q

How many mutations are required for malignancy ?

A

A combination affecting multiple TS genes and proto-oncogenes - exact number isnt known but thought to be less than 10

277
Q

How can the fact that many mutations are need to cause neoplasm be shown?

A

Adenoma carcinoma sequence
Analysis of early adenomas, later adenomas, primary carcinomas and metastatic carcinomas shows that mutations accumulates during this sequence over decades

278
Q

What is progression?

A

Steady accumulation of multiple mutations in cancer

279
Q

What are the six hallmarks of cancer?

A

1) self sufficiency of growth signals
2) resistance to stop growth signals
3) no limit in the number of times a cell can divide
4) sustained ability to produce new blood vessels
5) resistance to apoptosis
6) ability to invade and produce metastases

280
Q

Describe the model of cancer pathogenesis

A

Somatic cells are exposed to enviromental carcinomas that are either intiators or promoters culminating in a monoclonal population of mutatant cells. By chance some of these mutations affect proto-oncogenes or a tumour supressor gene whose protein transcription plays a crucial role in cell signalling pathway affecting hallmark changes. During progression the cells aquire further activated oncogenes or inactivated tumour supressor genes including ones that cause genetic instability. Cells have then aquired all the halmarks of cancerous cells.

281
Q

Give 2 occupations associated with the development if tumours and give the carcinogenic agent in each case

A

Office worker - asbestos –> lung cancer - malignant mesothelioma
Dye manufacturing - 2-napthylamine

282
Q

Give 3 examples of carcinogenic viral infections.

Give specific mechanisms

A

Hep B
associated with hepatocellular carcinoma
viral DNA integrated into host genome
Causes liver cell injury/regnerative hyperplasia
Increase in cell division gives increased risk of mutation
Epstein Barr
Associated with Burkitts lymphoma, some hodgkins lymphoma
Infects epithelial cells or oropharynx and B cells
Viral genes dysregulate normal proliferative and survival signals
Acquistion of mutation potiental

283
Q

What type of gene does the two hit hypothesis refer too?

A

Tumour supressor genes

284
Q

Describe the C-myc and HER 2 genes

A 
c-myc 
Binds to DNA stimulating synthesis 
Amplified in neuroblastoma, breast cancer
Translocatiion 8 to 14 in Burkitts lymphoma
HER-2
Encodes for growth factor receptor
Amplified in 25% of breast cancer
Herceptin if competative antagonist
285
Q

What genes maintian genetic stability?

A

Caretaker genes - belong to class of tumour supressor gene

286
Q

Describe 3 conditions that pre dispose tumours and the cancer types that commonly arise?

A

Ulcerative colitis
Colorectal carcinoma - damage DNA and microstatilite instability
Cirrhosis
Present in 85-90% of hepatocellular carcinoma, some association due to chronic viral hepatitis
Adenoma of colon or rectum- adenocarcinoma

287
Q

What is burkitts lymphoma ?

A

Transformation of B cells making genetic changes that lead to unlimited cell division

288
Q

What sorts of cancer is an early first pregnancy related to ?

A

Decreased risk of breast cancer - progestarone has a protective effect and increased risk of cervical cancer as oestrogen causes a proliferative response in the uterus

289
Q

What sort of cancer is schistomiasis associated with ?

A

Inflammation of the bladder wall which causes squamous metaplasia - increased risk of bladder cancer

290
Q

What sort of cancer is malaria associated with?

A

Burketts lymphoma - immune system compromised - Epstein Barr virus
Malaria parasite can cause replication of B cells and activation of EBS which is dominant

291
Q

What sort of cancer is aflatoxins associated with?

A

Liver carcinoma due to mutagenic effects

292
Q

What diseases can be caused by astebestos?

A

Mesothelioma
Bronchial carcinoma
Pleural plaque
Pleural fibrosis

293
Q

After exposure to asbestos how long does it take for mesothelioma to develop

A

20-50yrs

294
Q

What is the most important factor in determining prognosis of malignant melanoma ?

A

Depth of invasions

295
Q

How many new cases of cancer were there in 2008? How many deaths did this relate to?

A

13 million new cases leading to 7.6 deaths

296
Q

What 4 cancers account for over half of the cancers in the UK? What are their five year survival rate?

A

Lung (22%) , bowel (10%) , breast(7%) and prostate (7%)

297
Q

What proportion of cancers were diagnosed in the over 65 age bracket?

A

more than 60%

298
Q

In children younger than 14 what are the most common types of cancer ?

A

CNS tumours and lymphomas

299
Q

In men what cancers have the highest five year survival rate?

A

Testicular - 95%
Hodgkins lymphoma- 84%
melanoma - 78%

300
Q

In men what cancers have the worst five year survival rate?

A

Pancreatic -3%
lung - 6%
oesphageal - 7%

301
Q

In women what cancers have the highest five year survival rate?

A

Melanoma - 90%`
Hodgkins lymphoma -83%
breast- 79%

302
Q

In women what cancers have the worst five year survival rate?

A

Pancreatic - 2%
lung- 6%
oesphageal - 8%

303
Q

What factors are used to determine the outcome of a tumour?

A

Age, general health status, tumour site, tumour type, the grade ( differentiation) and stage and avaliablility of treatment

304
Q

Explain the most common method of tumour staging

A 
TNM
T- primary tumour size (T1-T4)
N- regional node metastases (N0-N2)
M- distant metastise (M0-M1)
This is then converted into a stage I-IV
305
Q

Describe the staging of a tumour I-IV

A

I- early local disease
II- advanced local disease
III- regional metasteses
IV- advnaced sdisease with distant metastases

306
Q

What staging system is used for lymphoma? Describe the stages ?

A

Ann Arbor
1- single node region
2- two separate regions on one side of the diaphragm
3- both sides of the diaphragm
4- diffuse or disseminated invovelment of one or more extra lymphatic organs such as bone marrow or lungs

307
Q

What is staging used for?

A

Powerful predictor of survival

308
Q

What staging is used for colorectal carcinoma?

A 
Dukes 
A- invasion into but not through the bowel wall
B- invasion through the bowel wall
C- involvement of lymph nodes 
D- distant metastases
309
Q

What does grading of a tumour describe ? What is the system?

A 
How differentiated it is - ie how much it looks like the parent tissue 
G1- well differentiated 
G2- moderately differentiated 
G3- poorly differentiated 
G4- anaplastic
310
Q

What is the problem with grading ?

A

Subjective not as well defined as staging

311
Q

What is the method of grading breast cancer? Describe it ?

A 
Bloom - richard system 
Assesses 
tubule formation - glandular tissue
Nuclear variation - pleomorphism
Number of mitoses
312
Q

What is tumour grading important for?

A

Planning treatment and estimating prognosis in certain types of cancer including soft tissue sarcoma, primary brain tissue, lymphomas and breast/prostate cancer

313
Q

What are the main treatments of cancer?

A

Surgery, radiotheraphhy, chemotherapy, hormone therapy, and treatment targetted to specific molecular alterations

314
Q

What is the main choice of treatment ? Why is it used?

A

Surgery
Small tumour - used as a cure
Large tumour - pallatively

315
Q

What is meant by adjuvant treatment?

A

AFTER surgical removal of a primary tumour to remove subclinical disease

316
Q

What is meant by neoadjuvant treatment ?

A

Given to reduce size of a primary tumour prior to surgical excision

317
Q

Describe the process of radiation?

A

Kills proliferating cells by triggering apoptosis or interferring with mitosis in rapidly dividing cells (especially those in G2) - focused on the tumour to protect healthy tissue
Give in fractional doses to decrease damage
Dosage either induces DNA damage directly or indirectly that is detected and apoptosis prompted.
Get double stranded breakages which cause chromosomes that prevent M phase from completing properly

318
Q

Describe the process of chemotherapy

A

Antimetabolites- mimic normal substrates involved in DNA replication
Alkylating and platinum based drugs cross link the two strands of the double helix
Antibiotics act in various ways inhibit DNA topoisomerase needed for DNA synthesis and others cause double DNA strand break
Plant derived drugs block microtubule assembly and interfere with mititotic spindle formation

319
Q

Give some examples of where hormone theraphy is used to treat malignancies

A

Selective oestrogen receptor modulators eg tamoxifen bind to oestrogen receptors preventing oestrogen from binding reducing the growth rate of receptor positive breast tumours as oestrogen is needed -( tamoxifen is acting as an antagonist)
Androgen blockage is used for prostate cancer

320
Q

Describe what is meant by oncogene cancer therapy

give two examples

A

Identifying cancer specific alterations - opportunity to target cancer cells specifically
Trastuzumub(herceptin) - HER-2 gene over expressison in 1/4 and this blocks HER-2 signalling
Imatinib( Gleevec)- chronic myeloid leukaemia shows chromosome rearrangement creating philadelphia chromosome in which an oncogenic fusion protein encoded imatinib inhibits this

321
Q

Describe the function of tumour markers

A

useful in monitoring tumour burden and effectiveness of treatment

322
Q

Where may tumour markers be measured?

A

Blood, urine, tissue

323
Q

What are the classes of tumour markers? Give and example of each and what releases them?

A

Hormones - testicular tumours –> human chorionic gonadotrophin
Oncofetal antigens - hepatocellular carcinoma –> alpha fetoprotein
Specific protiens - prostate carcinoma –> prostate specific carcinoma
Mucins/glycoproteins - ovarian cancer –> CA -125

324
Q

For what cancers are there established screening programmes?

A

Breast, cervical and bowel

325
Q

What are the problems with screening?

A

Lead time bias - diagnosed earlier so the survival time appears greater but treatment no difference to point of death
Length bias- screening is biased towards picking up slower growing cancers
Over diagnosis- false positive results puts people through unnecessary worry and testing - would never have presented as a clinical problem.

326
Q

Give 3 examples of tumour markers for 3 types of cancer and give their most common use

A

Carcinoembyronic (CAE)- colorectal and breast cancer used to check spread recurrence
Beta- human chrionic gonadotrophin- related to choriocarcinoma and testicular cancer used to assess stage, prognosis and treatment response of cancer
Alpha fetoprotein- liver and germ cell tumours
used to diagnose and determine response to treatment of liver cell cancer
Used to assess stage, prognosis and repsonse to treatment of germ cell tumour

327
Q

Describe the process of cervical cancer screening.

Who is invited and when

A

Cytological smears to look for any cervical intraepithelial neoplasm.
First invite at 25 and then every 3 years until reach 50-64 when its every five years.
Older than 65+ those who havent been screened since 50 or tose who have had recent abnormalitity

328
Q

Describe the process of breast cancer screening

A

Mammogram taken- X ray in two planes to identify invasive cancer before they can be felt identify densities and calcificaiton
Screened every 3 years from 50-69

329
Q

What are the major consequences of taking Tamoxifen ?

A

Increased risk of endometrial cancer - increased hyperplasia as partial agonist to oestrogen receptors in uterus

330
Q

How and when are people screened for bowel cancer/

A

Faecal occult blood test - see if blood in faeces then colonoscopy
60-69 every 2 years

331
Q

Define inflammation

A

Response to injury of vascularised living tissue to deliver defensive material to the site of injury protecting the body against infection and clear damaged tissue intiating repair

332
Q

Give some of the properties of acute inflammation

A

Innate sterotyped and rapid

333
Q

What are the causes of acute inflammation?

A 
Foreign bodies
Immune response
Infections and microbial toxins
Tissue necrosis
Trauma
Physical and chemical agents
334
Q

What are the clinical signs of acute inflammation? What causes them?

A

Rubor- redness caused by the dilation of blood vessels
Color- head caused by dilation of blood vessels
Tumour- swelling caused by infiltration of fluid and leucocytes in tissue
Dolor- pain caused by specalised nerve ending stimulated by mediators- bradykinin
Loss of function- enforces rest and decreases change of further damage

335
Q

Describe the formation of exudate

A

1) vasoconstriction of arterioles lasting just a few seconds
2) vasodilation of arterioles brought about by vasoactive mediators - histamine and nitric oxide
3) Walls of the venules become leaky and plasma escapes through gaps between cells

336
Q

Where is histamine released from?

A

Granules of mast cells, basophils and platelets

337
Q

What is the effect of loss of fluid into the tissue on the flow in vessels?

A

Hampered blood flow and increased pressure up stream leading to up stream lumens dilating and further reduction in flow speed. The increased pressure causes more fluid out of venules.

338
Q

What does histamine do?

A

Acts as a neuortransmitter in the brain

Produces pain, arteriolar dilation and venular leaking by causing endothelial cells to contract and pull apart

339
Q

What does serotonin do that histamine doesnt?

A

Stimulate fibroblasts

340
Q

What is prostaglandin used for in acute inflammation? What is it produced from?

A

Vasodilation makes skin increased sensitive and causes fever

Produced from cell membrane phospholipids

341
Q

How does asprin and NSAIDs work?

A

Inhibit cyclo-oxygenase and phospholipases reducing production of prostaglandins therefore reducing fever

342
Q

What forces are involved in equilibrium of fluid exchange normally?

A 
Starlings law force involved in 
capillary pressure, 
interstital free fluid pressure
plasma colloid osmotic pressure
Intersitial fluid colloid osmotic pressure
343
Q

Define oedema

A

Excess fluid in interstitium- dilutes toxins released from pathogens

344
Q

What are the two types of oedema how do they vary?

A

Can be transudate (watery) or exudate (containing
proteins)
● Transudate more likely in oedema caused by hypertension rather
than inflammation
● Exudate contains proteins which can help to fight infection
– Immunoglobulins
– Inflammatory mediators
– Fibrinogen – for clotting

345
Q

What is the consequence of oedema?

A

Increased lymphatic drainage - lymph system plays key roles in immune response - lymph nodes and spleen contain lymphocytes which can help clear infection as exudate is transported to them

346
Q

How are the forces changed in acute inflammation?

A

Semipermeable membrane becomes leaky so main driving force out is increased and main driving force in is reduced as proteins escape until it equals blood.

347
Q

What defensive agents are found in the blood?

A

Opsonins - make things easier to phagocytose
Complement - produce bacteria perforating structre
Antibodies - bind to surfaces of microorgansim act as opsonins

348
Q

What chemical mediators induce vascular leakage?

A

Histamine, serotonin, bradykinin and complement components c3a, c4a, c5a

349
Q

Describe neutrophils

A

End cell cannot multiply, granulocytes, polymorphs

350
Q

What must neutrophils do to infiltrate a tissue

A 
Margination – Stasis of blood causes
neutrophils to line up at the edge of blood vessels along the
endothelial lining
– Rolling – Neutrophils roll along endothelium, sticking to it
intermittently
– Adhesion – Neutrophils stick
more avidly
– Emigration – Neutrophils
pass through vessel wall to
site of inflammation
351
Q

What are chemotaxins ? give some examples

A

They direct neutrophils to the area of damage by attracting neutrophils.
Include bacterial products, injuried tissue substance produce leucocytes- release leukotrienes and spilled blood

352
Q

How do neutrophils move?

A

by producing filopodia that pull back of cell in direction of extension

353
Q

What is neutrophil activation and how does it come about?

A

Switching to a higher metabolims level, increased stickness

Binding of chemotaxins which leads to influx of soduim and calcuim ions with water following

354
Q

How do neutrophils carry out diapedsis?

A

Diapedsis- crawling out endothelium

produce collagenase which digest the basement membrane

355
Q

What is recognition attachment?

A

Neutrophils recognise bacteria and stick to it

opsonins make the process easier

356
Q

Describe the process of phagocytosis

A

Engulf bacterium
Membrane of phagocytes form a crater shape around the particle leading to a cup surrounding particle the edges then come together and membrane fuses. The particles is then contained inside an intracellular vacuole and digested during degranulisation

357
Q

When does degranulation begin in phagoctyotsis ? What is the consequence of this?

A

Before particle completly enclosed leading to leaking into surrounding tissue and local tissue injury

358
Q

What methods are used in killing in phagocytosis?

A

O2 dependent and O2 independent

359
Q

Where are endogenous mediators supplied by?

A

Plasma, leuocyctes and local tissue

360
Q

Give some properties of mediators

A

Have inhibitors,short life span and effects are short lasted

361
Q

Give some vasoactive amines

A

Histamine and serotonin

362
Q

Give some vasoactive peptides

A

Bradykinin

363
Q

How is bradykinin produced?

A

Circulates in the blood as part of kininogen which when cleaved by kallirein produces bradykinin

364
Q

How do complement proteins circulate in the blood?

A

Number of dissembled proteins

365
Q

Give some mediators derived from phospholipids

A

Prostaglandins, thromboxanes and leukotrienes

366
Q

Give some cytokine and chemokines

A

Interleukins, TNF, interferons

367
Q

Give an exogenous mediator and what produces it and its consequence

A

Endotoxin- produced by gram negative bacteria which if in blood causes septic shock

368
Q

Give the roles of mediators

A

Vasodilation, increased vascular permeability, chemotaxis, phagocytosis, pain

369
Q

What constitutes can effective response to injury?

A 
Delivery of antibodies, nutrients
Dilution of toxins
Maintainence of temp
Stimulation of immune response
destruction and removal of dead or foreign material
370
Q

What are the local complications of acute inflammation?

A

Damage to local tissue
obstruction of tubes and compression of vital structures
loss of fluid- important in burns
pain and loss of function

371
Q

What are the systemic complications of acute inflammation?

A

Fever caused by pyrogenic cytokines - can be useful bacteria temperature susceptible and inflammation increased effecient at higher temps
Leucocytosis - increased number of leucocytes circulating due to increased CSF production
Acute phase response - produced by cytokines leading to sleepiness, loss of appetite and change in some levels of plasma proteins due to altered synthesis
shock - bacterial products spread in around body

372
Q

How is acute inflammation resolved?

A

Mediator levels fall and cessation leads to return of normal vascular conditions and other phyiological conditions - neutrophils apoptose
Scar may form if parenchymal cells cannot regenerate

373
Q

What are the three types of exudate ?

A

Pus- creamy white lots of neutrophils seem in chemotactic bacteria
Haemorrhagic - enough red blood cells to appear bloody to the naked eye- significant vascular damage seen in destructive infections or when exudate result of infiltration by malignant tumour
Serous - plasma proteins clear and seen in blisters
Fibrinous - significant deposition of fibrin - head as a rubbing sound when in pericardial or pleural sac as can no longer slide over each other

374
Q

What is seroma?

A

Tissue space filled with clear sterile fluid that occurs post op

375
Q

What is hereditary angio-oedema?

A

Autosomal dominant conditon- deficiency of c1 esterase inhibitor leading to reduced levels of C2 and C4. patients have attacks of non itchy cutaneous angiooedema ( rapid oedema of dermis, subcutaneous tissue, mucosa and submuscosa tissue), recurrent abdo pain and intestinal oedema.
May have family history of sudden death due to laryngeal involvement

376
Q

What is alpha 1 anti-trypsin defiency?

A

Autosomal recessive
low serum levels of this protease inhibitor resulting in emphysemia due to elastase acting unchecked. Also get liver disease as synthesized in hepatocytes and gets abnormally folded which leads to polymerisation causing retention in ER promoting autophagocytosis and hepatitis/ cirrhosis/jaundice

377
Q

Describe chronic granulomatous disease?

A

X linked or autosomal recessive
Phagocytes are unable to generate free radical superoxide
Bacterias are phagocytosed byt phagocyte unable to kill them as cannot generate O2 burst leading to chronic infection in first year of life
Get numerous granulomas and abscess affecting most tissues and osteomyelitis

378
Q

What is lobar pneumonia?

A

Inflammation of the lungs with exudate and consolidation. Seen in all or part of a lobe with other areas generally normal
Caused by streptocoocus pneumoniae -Pneumococcus, gram positive diplococci, lancet shaped

379
Q

Describe the process of development of pneumonia ?

A

1) congestion
2) red hepatisation
3) Gray hepatisation
4) resolution

380
Q

What are some of the complication of pneumonia?

A

Absces, fibrosis, emphysema, dissemination resulting in meningitis , arthritis, infective endocarditis

381
Q

What are the complications of acute appenditicis ?

A

Peritonitis, death, abscess, septicaemia, fistula

382
Q

What are the predisposing factors to appendicits?

A

Gender, family history, age, low fibre diet, GI infection

383
Q

What is the major cause of meningitis in neonates?

A

Group B streptococci, E coli, listeria monocytogenes, streptococci agalactiae

384
Q

What is the major cause of meningitis in children?

A

Neisseria meningitis, streptococci pneumonia, haemophlilis influenza type B

385
Q

What is the major cause of meningitis in young adults?

A

Neisseria meningitis

386
Q

What is the major cause of meningitis in older age groups?

A

Listeria monocytogenes

387
Q

What is the link between gallstones and hepatic abcesses ?

A

Bile ducts are blocked so no transport of bile to gall bladder from liver leading to the build up of bile and chronic inflammation. Bile is a good culture medium so get bacteria there and then inflammation leads to abscess.

388
Q

What is disease a result of?

A

Intrinsic and extrinsic abnormalities or a combination of both

389
Q

What happens to cells during changing their enviroment?

A

Mild changes - able to maintain homeostasis
Increase severe - undergo physiological and morphological adaptations to remain viable eg increased or decreased activity
When can no longer change may show reversible or irreversible cell damage leading to cell death

390
Q

What are some of the causes of cell injury?

A

Hypoxia- decreased aerobic oxidative respiration due to o2 deprevation
Physical agents eg direct trauma, extreme temp, sudden changes in atmospheric pressure and electrical currents
Chemical agents and drugs - glucose or salt in hypotonic solution, O2 at high conc, poisons, insecticides, asbestos, alcohol and drugs
Mircoorganisms
Immune mechanism- over vigorous reaction and autoimmune
Dietary insufficiencies and deficiency
Genetic abnormalities

391
Q

What are the causes of hypoxia?

A

1) hypoxaemia - low arterial o2 conc
2) anaemia - decreased ability to carry o2 - CO poisoning
3) Ischaemia
4) histiocytic- inability of the cells to use o2 due to disabled oxidative phosphorylation enzyme (CN- binds with mitochondrial cytochrome oxidase)

392
Q

What are the sites of cell injury?

A

Cell membrane - plasma and organelle- especially lysosmes as these contain potent enzymes
Nucleus
Proteins - structural proteins that form cytoskeleton and enzymes involved in metabolic processes
Mitochondria - oxidative phosphorylation

393
Q

Describe reversible hypoxic injury

A

Reduced O2 to cell - decreased production of ATP by OP in mitachondria leading to Na pump stopping working leading to increase in intracellular conc and water drawn in - ONCOSIS.
Increased Na leads to a reverse in NCX channel and Ca in.
Reliance on glycolytic respiration leads to a decreased pH affecting enzymes and chromatin clumping ( activation of heat shock response)
Ribosomes detach from ER leading to disruption in protein synthesis and intracellular accumulations of substances

394
Q

Describe irreversible hypoxia injury

A

Disturbances in membrane integrity leads to increased permeability so HUGE increase in Ca from extracelluar, ER and mitachondria. The increase in Ca leads to activation of many enzymes that cause further damage,
Get enzyme leak from lysosomes - into circulation used for diagnosis
Cell membrane starts to show blebbing

395
Q

Describe ischaemia reperfusion injury

A

Blood flow back to an area of ischaemic but not yet necrotic tissue - damage is worse than if no blood flow back

396
Q

Why does ischaemic reperfusion injury occur

A

Increased production of radicals with reoxygenations
Decreased number of neutrophils resulting in increased inflammation and tissue injury
Delivery of complement proteins and activation of complement pathways

397
Q

What are free radicals? What free radicals are found in the body?

A

Reactive oxygen species - single unpaired electron

OH, O2- and H2O2

398
Q

When are free radicals produced?

A

Chemical and radiation injury, ischaemic reperfusion injury, cellular aging and high o2 conc

399
Q

What damage do free radicals do?

A

Attack lipids in the cell membrane causing lipid perioxidation - molecules become bent broken and cross linked
Also affect carbohydrates and nucleic acids

400
Q

How is OH radical produced?

A

Radiation directly lyses water
Fenton and Harber Weiss reaction use metal to produce them from other free radicals - why its really important to remove other radicals.

401
Q

Describe the body’s natural anti-oxidant system

A

SOD- O2- into H2O2
Catalases and perioxidases
Free radical scavengers -vit ACE and glutathione
Storage proteins - sequester transitions metals in extra cellular matrix decreasing production

402
Q

Give an example of a heat shock protien

A

Ubiquitin

403
Q

What is the function of heat shock proteins

A

Protect against injury- act as chaperones and re fold incorrectly folded proteins
They recognise incorrectly folded proteins and repair them- if unable to repair then they initate the destruction of that protein
important in maintaining protein viability and increase chance of survival

404
Q

Where are heat shock protein found? What changes during cell injury?

A

They are found within the cell - they are not secreted
During cell injury the concentration found in a cell increases due to increased synthesis and decreased synthesis of other proteins

405
Q

What 3 alterations are seen under the light microscope during cell death

A

Cytoplasmic changes - decreased pink staining due to oncosis followed by increased staining due to accumulation of denatured proteins
Nuclear changes - chromatin clumping followed by pyknosis, karryohexis and karrolysis
Abnormal cell accumulation

406
Q

What is pkynosis?

A

nuclear shrinkage

407
Q

What is karryohexis?

A

Nuclear fragmentation

408
Q

What is karryolysis?

A

Nuclear dissolution

409
Q

With an electron microscope what reversible changes are seen in cell injury?

A

Swelling, cytoplasmic blebs. clumped chromatin, ribosome separation from the ER

410
Q

With an electron microscope what irreversible changes are seen in cell injury?

A

Increased cellular swelling, nuclear changes , swelling and rupture of lysosomes, membrane defects, appearance of myelin figures, lysis of the ER, amorphous denisties in swollen mitachondria

411
Q

Define oncosis

A

Cell death with swelling - spectrum of changes that occur prior to cell death in cells

412
Q

Define apoptosis

A

Cell death with shrinkage, cell induced by regulated intracellular program where a cell activates enzymes that degrade own nuclear DNA and proteins

413
Q

Define necrosis

A

Morphological changes that occur after a cell has been dead for some time- appearance largest due to progressive degradative action of enzymes on dead cells

414
Q

Why do you get an inflammatory response in necrosis ?

A

Leakage of cellular content into extracellular space

415
Q

How is necrotic tissue removed? What happens if this isnt complete?

A

By phagocytosis and if not complete it will calcify leading to dystrophic calcification

416
Q

What types of necrosis are there?

A

Coagulative - proteins undergo denaturation, clumping of dead cells seen in solid organs , white to the naked eye, proteins uncoil and become less soluble
in first few days you see ghost outline of cells
Liquifactive - proteins dissolve in cells own enzymes autolysis, seen in massive neutrophil infiltration, abscess and bacterial infection
seen in the brain - fragile tissue without support from robust collagenous matrix
Caseous - cheesy appearance, characterised by amporphous debris - TB and granulomatous
Fat- destruction of adipose tissue seen in acute pancreatitis( release of FA which react with Ca ions forming chalky deposits in fatty tissue) and breat trauma (confused with cancer)

417
Q

What is gangrene and where is it common?

A

Necrosis visible to the naked eye - most common in ischaemic limbs

418
Q

What are the different types of gangrene ? What determines the type that occurs?

A

Wet- liquifactive necrosis -very serious as bacteria can enter the blood stream and cause septicaemia
Dry- bacteria unable to grow in dry tissue and therefore linked with coagulative necrosis
Gas- tissue infected by anaerobic bacteria producing visible and palpable bubbles of gas within tissue
Depends on whether necrosis is modifiec by exposure to the air or bacteria

419
Q

What is an infarct?

A

An area of necrosis where ischaemia is caused by obstruction of a tissue’s blood supply usually due to thrombsis, embolism, compression or twisting of vessel can result in gangrene.

420
Q

How are infarcts classed?

A

How much haemorrhaging occurs into the tissue

421
Q

Describe a white infarct

A

solid organs after occlusion of end artery- nature limits the amount of haemorrhaging that can occur

422
Q

Describe a red infarct and its causes

A

extensive haemorrhaging into dead tissue when
o Dual blood supply e.g. lungs – secondary arterial supply insufficient to rescue tissue but allows blood in
o Numerous anastomoses e.g. intestines – capillary beds of 2 separate arterial supplies merge
o Loose tissue e.g. lung – poor stromal support for capillaries
o Previous congestion – congestive heart failure results in more than usual amounts of blood in tissue
o Raised venous pressure – increased pressure transmitted to capillary bed as tissue pressure increases eventually arterial pressure falls causing ischaemia and necrosis resulting in red infarct as tissue engorged with blood

423
Q

What does the consequences of ischaemia depend on?

A
  • Whether alternative blood supply
  • How rapidly occurred – time for development of alternative pathway of perfusion
  • How vulnerable tissue is to hypoxia
  • O2 conc of blood – increase severe in anaemia
424
Q

What molecules may be released by cells during cellular injury

A
  • Potassium – high conc in compared to outside, heart stops with high conc- used in cardiac surgery, released after MI, massive necrosis and successful chemotherapy
  • Enzymes – indicate organs involved, extent, timing, and evolution, SMALLEST MOLECULAR WEIGHT RELEASED FIRST
  • Myoglobin – dead myocardium and striated muscle, can plug renal tubes causing kidney failure.
425
Q

What happens if large amount of myoglobin are released from striated muscle? When is this seen?

A

rhabdomyolysis occurs – seen with severe burns, strenuous exercise, potassium depletion, substance abuse

426
Q

Describe apoptosis

A

Cell death with shrinkage death of single cell due to activation of internally controlled suicide programme- characterised by non-random internucleosomal cleavage of DNA
Can be a physiological process –cells no longer required removed to remain in steady state, hormonal controlled involution and cytotoxic killing of virus infected or neoplastic cells. Occurs when cell is damaged especially affecting DNA toxic injury and tumour
Cell activates enzymes to degrade own nuclear DNA and proteins – membrane integrity is maintained, requires energy, lysosomal enzymes are not released, quick

427
Q

What is seen under the light microscope during apoptosis?

A

shrunken and appear intensely eosinophilic, chromatin condensed, pykinosis and karyorrhexis , affects single or small cluster of cells

428
Q

What is seen under the electron microscope during apoptosis?

A

cytoplasmic budding  fragmentation into membrane bound apoptotic bodies which are eventually removed by macrophages

429
Q

What are the three stages of apoptosis?

A

initiation, execution and degradation/phagocytosis

430
Q

Describe intiation and execution of apoptosis?

A

Intrinsic and extrinsic pathways which culminate in activation of caspases – proteases that mediate cellular effects of apoptosis act by cleaving proteins breaking up the cytoskeleton and initiating degradation of DNA.
• Intrinsic – mitochondrial central player all machinery within cell- various triggers DNA damage or removal of growth factors or hormones and p53 which lead to increased mitochondrial permeability and release of cytochrome c that interacts with APAF1 and caspase 9 forming an apoptosome and activation of downstream caspases
• Extrinsic – external ligands TRAIL and Fas bind to death receptors – caspases are activated independently of mitochondria.

431
Q

Describe degradation of apoptosis

A

Cell breaks into membrane bound fragments – apoptotic bodies express molecules on surface that induces phagocytosis by neighbouring cells and phagocytes.

432
Q

What are the important molecules in apoptosis

A

 P53- mediates apoptosis in response to damaged DNA
 Cytochrome c, APAF1, caspase 9- apoptosome
 BCL 2- prevents cytochrome c release – inhibits apoptosis
 Death ligands and death receptors
 Caspases – effector molecules of apoptosis e.g. caspase 3

433
Q

What are abnormal cellular accumulations derived from?

A

 Cells own metabolism
 Extracellular space
 Outer environment

434
Q

What are the abnormal cellular accumulations?

A

Fluid
Lipids
proteins
Pigments

435
Q

Describe fluid as an abnormal cellular accumulation

A

appear as discrete droplets or diffuse waterlogging of entire cell resulting in cell swelling due to osmotic disturbances – occur when energy supply cut off and indicates distress. Can cause compression consequences e.g. blood vessels in brain.

436
Q

Describe lipids as an abnormal cellular accumulation

A

steatosis – accumulation of TAGs, 1st stage of alcoholic liver disease, increased size of organ, mild – clinically asymptomatic – no cell effects and reversible
Can be diagnosed with naked eye- yellow colour
• Cholesterol – cannot be broken down by the body, insoluble, only excreted through liver, excess stored in membrane bound droplets, accumulation within SM and macrophages – atherosclerotic plaques Microscopically – cells have foamy appearance known as foam cells, seen in xanthomas
• Phospholipids disrupted in cell membrane – myelin figures

437
Q

Describe proteins as an abnormal ceullular accumulation

A

seen as eosinophilic droplets or aggregations in cytoplasm
• Mallory’s hyaline damaged proteins seen in hepatocytes in alcoholic liver disease – accumulation of keratin filaments
• Alpha 1 antitrypsin deficiency- liver produces incorrectly folded alpha 1 antitrypsin which cannot be packaged by ER so accumulates and is not secreted  proteases act unchecked leading to emphysema

438
Q

Describe exogenous pigmentations as a abnormal cellular accumulation

A
  • Carbon, coal, soot once they are inhaled phagocytised by macrophages within lung tissue can be seen as blackened lung tissue or as blackened peribronchial lymph nodes – permanent discolouration, usually harmless but high exposure lungs can become fibrotic or emphysematous .
  • Tattoos – pigment phagocytised by macrophages in the dermis remains there indefinitely – some drained into the lymph nodes
439
Q

Describe endogenous pigmentations as a abnormal cellular accumulation

A

• Lipofuscin – age pigment, brown seen in aging cells, no injury caused – sign of previous free radical injury and lipid peroxidation, consists of a polymer of oxidised indigestible brownish intracellular lipid, only seen in long lived cells
• Haemosiderin – iron storage molecule derived from haemoglobin, forms when systemic or local excess of iron e.g. bruise. If systematic overload of iron haemosiderin deposited in many organs called haemosiderosis (seen in hereditary haemochromatosis- increase absorption of iron in intestines)
Haemochromatosis iron is deposited in skin, liver, pancreas, heart and endocrine organs  bronze diabetes
• Bilirubin- must be removed when bile flow obstructed or overwhelmed increased bilirubin leads to jaundice- deposited in tissues extracellular or in macrophages
Bilirubin can be made anywhere in the body and it is very toxic

440
Q

Define calcification

A

abnormal deposits of calcium salts within tissues – can be local or general dystrophic or metastatic

441
Q

Describe dystrophic calcification ie when and what changes

A

– area of dying tissue, atherosclerotic plaque, aging or damaged heart valves and tuberculous lymph nodes.
Local changes in tissue favours nucleation of hypoxyappatite crystals leading to organ dysfunction

442
Q

Define metastatic calcification

A

disturbances body wide crystals deposited in normal tissue throughout the body when hypercalcaemia secondary to disturbances in calcium metabolism

443
Q

What are the causes of metastatic calcification

A

Increased PTH levels and therefore bone reabsorption
• Primary parathyroid hyperplasia or tumour
• Secondary renal failure retention of phosphate
• Ectopic secretion of PTHrp by malignant tumour
Destruction of bone tissue
• Primary tumour of bone marrow
• Diffuse skeletal metastases
• Pagets disease of bone – accelerated bone turnover
• Immobilisation

444
Q

What is seen during cell aging?

A

Damage to cellular constitutes and DNA- get lipofusion and other abnormally folded proteins
Decreased ability to replicate – replicative senescence – cannot divide independently – relates to chromosome length, during every replication telomere gets shorter at a critical point no longer able to divide

445
Q

What do stem cells and cancerous cells possess to enable them to replicate indefinately?

A

telomerase

446
Q

Describe the stages of alcoholic liver disease

A

• Fatty change – affects fat metabolism  steatosis marked as a cause to hepatomegaly ( reverse acute change)
• Acute alcohol hepatises- alcohol and metabolites directly toxic – binge results in acute hepatitis with local hepatocyte necrosis, formation of Mallory bodies and neutrophil infiltration
Symptoms – fever, liver tenderness, and jaundice – reversible
• Cirrhosis – hard shrunken liver and microscopically micro-nodules of regenerating hepatocytes surrounded by bands of collagen. Irreversible and serious

ESA two revision (4 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions