Cellular Pathology

Front 1

Potential causes of cellular injury (8)

Back 1

- Hpoxia
- Physical agents
- Chemical agents
- Nutritional
- Genetic (direct or indirect (increasing susceptibility to other diseases)
- Workload ibalance
- Immunologic

Front 2

Hpoxia

Back 2

Partial reduction in oxygen supply to cells

Front 3

What factors affect the response to cellular injury? (4)

Back 3

Severity, cell type, natre of agent and duration of injury.

Front 4

Hyperplasia

Back 4

Increase in number of cells.

Front 5

Hypertrophy

Back 5

Increase in size of cells

Front 6

Metaplasia

Back 6

One cell type is replaced by another, less well differentiated.

Front 7

Squamous metaplasia

Back 7

irritation to respiratory tract causes respiratory epithelium to die. It is replaced by more protective squamous cells. Loss of function.

Front 8

Dysplasia

Back 8

Alteration in size, shape and organisation of cells.

Front 9

Atrophy

Back 9

Decrease in size of cells.

Front 10

Fatty change

Back 10

Accummulation of intracytoplasmic lipid in response to insults which alters the cells ability to metabolise normally.

Front 11

Lipidosis

Back 11

Accummulation of fat in cells, taken up from blood in situations of negative energy balance.

Front 12

Hydropic degeneration

Back 12

Cellular swelling

Front 13

What is hydropic degeneration caused by?

Back 13

Hypoxia

Front 14

Pathogenesis of hydropic degeneration?

Back 14

Reduced ATP > switch to anaerobic respiration > depletion of glycogen, build up of lactic acid and inorganic phospahtes > INHIBITION OF NA K PUMP > water moves into cell.

Front 15

What is the morphology of cells with hydropic degeneration?

Back 15

Vacuolated cytoplasm.

Front 16

In hydropic change, is cell swelling reversible?

Back 16

Yes but can progress to death is stimulus is not removed.

Front 17

Which cells are particularly sisceptible to hydropic change?

Back 17

Hepatocytes, renal tubular epithelium, cardiac myocytes, endothelial cells.

Front 18

Oncotic necrosis

Back 18

death by swelling. Damaged cells do not necessarily die but if injury is severe/prolonged necrosis occurs due to raised intracellular calcium levels.

Front 19

Coagulative necrosis

Back 19

-Characteristic of hypoxic death
- Basic cell outlines are preserved due to delayed proteolysis
- acute

Front 20

Caseous necrosis

Back 20

- Chronic
- Cheese like
- Tuberculosis

Front 21

Liquefactive necrosis

Back 21

- cavities filled with liquefied debris
- Abscesses
- found in CNS - little fibrous framework to support dead cells

Front 22

Gangrenous necrosis

Back 22

- Follows on from coagulative necrosis
- Moist - saprophytes
- dry - mummification
- gas - saprophytes

Front 23

Fat necrosis

Back 23

necrosis of fat

Front 24

Ischaemia

Back 24

Perfusion is lowered relative to tissues metabolic needs (eg. hypoxia).

Front 25

Infarct

Back 25

Localised tissue necrosis resultong from Ischaemia.

Front 26

Pyknosis

Back 26

Nucleus is small, shrunken, dense

Front 27

Karyorrhexis

Back 27

Nucleus disintergrates (EXPLODES)

Front 28

Karyolysis

Back 28

Lysis of nucleus

Front 29

Labile cells

Back 29

continuously dividing, eg. bone marrow

Front 30

Stable cells

Back 30

Can undergo rapid divison if required, eg. liver cells

Front 31

Permanent cells

Back 31

Permanently left cell cycle, cannot undergo meiosis. eg. neurons in CNS

Front 32

What are the characteristics of apoptic cells? (3)

Back 32

Chromatin condenses, fragmentation of cytoplasm, apoptic bodies in cytoplasm.

Front 33

Necrosis

Back 33

cell death due to traumatic damage - messy

Front 34

Apoptosis

Back 34

Cell death managed and programmed.

Front 35

Give examples of pruning in embryonic development.

Back 35

- only neurons that reach muscle cells in limb bud will survive, myoblasts secrete neurotrophins which act as survival signals

- Only T-cells with affinity for foreign antigen live, T-cells with no affinity or affinity fro self will be killed.

- digits formed by apoptosis of cells between them

- mesonephrous duct largely dissappears by apoptosis (embryonic kidney)

Front 36

What does the paramesonephrous duct develop into? (medial)

Back 36

Fallopian tube

Front 37

What does the mesonephric duct develop into? (more lateral)

Back 37

Vas deferens

Front 38

How is tissue homeostasis maintained by apoptosis?

Back 38

- liver regenerates itself to original size if it is reduces or increases in size
- cell division and cell death must be balanced
- body knows correct size of a tissue

Front 39

Explain the improtance of apoptosis in virally infected cells?

Back 39

viral antigen shown by APC to T-cell, apoptsis occurs

Front 40

Does the cell membrane erupt in apoptsis?

Back 40

Cell membrane does not erupt

Front 41

What happens to apoptic cells?

Back 41

They shrink, lose contact with their neighbours, start blebbing and produce apoptic bodies.

Front 42

What happens to apoptic bodies?

Back 42

Phagocytosed by other cells.

Front 43

In apoptosis the chromosomes condense and do what?

Back 43

Attach to nuclear envelope

Front 44

Is there an inflammatory response in apoptosis?

Back 44

No

Front 45

What happens in necrosis?

Back 45

Cells swell, cell membrane damaged, loss of cell contents leading to an inflammatory response.

Front 46

What do gatekepper caspases do?

Back 46

INfluence many executer caspases leading to an amplification of the signal for apoptosis.

Front 47

What are gatekeeper caspases triggered by?

Back 47

Internal and external signals

Front 48

Is cell death the default of cells?

Back 48

Yes and it will occur in the abscense of survival signals.

Front 49

Caspases

Back 49

Calcium dependent proteases
- cut at aspartic acid residues
- activated by proteolytic cascades

Front 50

What are gatekeeper caspases?

Back 50

PROENZYMES
- require a scaffolding protein for autoactivation

Front 51

What activates caspase 8?

Back 51

A scaffold assembled at the cell membrane in response to external signals

Front 52

What activates caspase 9?

Back 52

A scaffold in the cytoplasm established by cytochrome C release from mitochondria, in response to internal and external signals.

Front 53

Apoptosomes

Back 53

Gatekeeper caspase scaffold

Front 54

Executer caspases

Back 54

Activated by gatekepper caspases, proteolytic enzymes, produce the changes of apoptosis,

Front 55

Uncorrectale DNA damage causes upregulation of what?

Back 55

p53

Front 56

What does pro-apoptotic BCl2 do?

Back 56

Forms a pore in mitochondria allowing release of cytochrome C.

Front 57

How can apoptosis be initiated? (e.g. via a T-cell receptor and MHC)

Back 57

- Formation of a perforin pore
- via a fas ligand and receptor forming a scaffold for GK caspase 8

Front 58

Neoplasia

Back 58

- cancer/tumour
- cells have undergone genetic changes
- cells are unresponsive to normal growth controls,
- expand beyond normal anatomival boundaries
- excessive growth persists even after stimulant is not present.

Front 59

What causes the genetic changes present in neoplastic cells?

Back 59

- single inherited mutated gene (very rare)
- Multiple inherited genes
- acquired somatic mutations

Front 60

Do Australians breed hereford cows with brown pigmentation around their eyes or no pigmentation?

Back 60

With brown pigmentation - cows without are more susceptible to neoplasms of the eyes/eye cancer. Aussie cows more likely to develop cancer becasue sun increases risk as well.

Front 61

Is neoplasm multifactorial or singly factorial?

Back 61

Multifactorial - integrated genes and somatic mutations can play a role.

Front 62

Where in the genome do genetic mutations occur? (5)

Back 62

- Growth factors and growth factor receptors.
- Signal transduction proteins (activate cellular growth)
- Transcription factors (act directly to increase gene expression)
- Anti-oncogenes (tumor suppressors turned off)
- DNA repair genes.

Front 63

Characteristics of benign tumours?

Back 63

Well differentiated,
Uniform cell size/shape
Normal nuclear morpology,
Few mitoses,
Encapsulated,
No metastases

Front 64

Characteristics of malignant tumours?

Back 64

Poorly differentiated,
Variable cell size/shape
Abnormal nuclear morphology
Increased mitoses
Non-encapsulated, infiltrive
Metastasises

Front 65

Anaplastic

Back 65

Poorly differentiated

Front 66

PLeomorphic

Back 66

cells are different sizes and shapes

Front 67

What do mitoses reflect?

Back 67

Rate of replication (high numer, high rate)

Front 68

Which malignant tumours do not metastasize?

Back 68

Tumours of CNS

Front 69

what are the direct effects of neoplasia on animals? (5)

Back 69

- compresses tissue,
compresses/blocks blood vessels
- block tubular organs
- organ rupture
haemorrhage

Front 70

What indirect effets do neoplasms have on animals?

Back 70

remote effects caused by products released by tumour (eg. cachexia)

Front 71

Cachexia is an example of what condition?

Back 71

Paraneoplastic syndromes

Front 72

Cachexia

Back 72

weight loss and debility, muscle and fat are lost at the same time, feeding up does not help

Front 73

What is cachexia likely to be casued by?

Back 73

cytokines, although unknown.

Front 74

Haemostasis

Back 74

arressment of bleeding

Front 75

Is the haemostatic mechanism always active?

Back 75

yes

Front 76

What are the 3 processed involved in haemostasis?

Back 76

1. clumpling of platelets to form a plug.
2. Vasoconstriction to slow escape of blood
3. Formation of a fibrin meshwork or clot

Front 77

What is plasma?

Back 77

serum with clotting factors, fluid part of blood.

Front 78

serum

Back 78

plasma without clotting factors

Front 79

Can plasma clot without platelets and blood cells?

Back 79

Yes but it is more rapid in the presence of platelets.

Front 80

What are platelets made from?

Back 80

Megakaryocytes

Front 81

What shaoe are platelets?

Back 81

Discoid

Front 82

What do platelets contain a lot of?

Back 82

Actin and Myosin - this allows them to change shape when they adhere to site of injury = platelet activation, can no longer slip through capillaries.

Front 83

Do platelets have a nucleus and organelles?

Back 83

No nucleus but yes they do have organelles. They have a role in secretion - contain glycogen granules.

Front 84

How is a plug fromed?

Back 84

Platelets bind to collagen. This requires von Willibrand Factor.

Front 85

What does degranulation of platelets release?

Back 85

ATP, ADP, and alpha-serotonin

Front 86

What does serotonin do when secreted from platelets?

Back 86

Causes vasoconstriction.

Front 87

What activates serotonin?

Back 87

Thrombin

Front 88

What does ADP do once released from platelet?

Back 88

Stimulates aggregation of platelets.

Front 89

Thromboxane is also formed and released. What does it do?

Back 89

Further stimulates aggregation.

Front 90

In which stage is thrombin activated?

Back 90

Third - clot formation

Front 91

PLatelets also bring about clot contraction. What is the effect and what does it involve?

Back 91

It pulls the clot tightly against the surface of the vessel. It involves actinomyosin.

Front 92

How are platelets self amplifying?
(Include Factor V, fibrinogen and thrombin)

Back 92

Platelets provide:
1. Factors - receptors for factor V which is released from alpha granules, promotes thrombin formation.
2. Surface - Factor V must bind to promote thrombin formation, also has receptors fro fibrinogen - thrombin turns this into fibrin which forms the clot.
3. Coagulation localised - all ingredients are attached to platelet.

Front 93

Arachidonate Metabolites

Back 93

Involved in clot contraction.
Fatty acid with a c=c, flexible
produces many messenger molecules

Front 94

What does prostacyclin do? What does it operate via?

Back 94

Inactivates platelets by inhibiting activation processes. Operates via adenylate cyclase and cAMP.

Front 95

What is aspirin

Back 95

anti pain, anti inflammatory drug. Used as a preventative against thrombosis.

Front 96

What does aspirin do?

Back 96

Blocks cyclo-oxygenase from forming prostaglandins
Blocks pathway to PGI2 (prostacyclin) and TXA2 (Thromboxine)
= in platelets this remains inhbited for life of the cell.
= the enzyme in endothelial cells has a more rapid turnover time

Increases tendancy to bleed

Front 97

Are clots static?

Back 97

no, there is a dynamic equilibrium which can be shifted either way.

Front 98

Prophylactic anticoagulant

Back 98

preventative - will reduce spread of clot, main value in preventing clots forming

Front 99

How can you test DNA to see if it contains an oncogene?

Back 99

It will grow in soft agar/form tumours

Front 100

v-onc

Back 100

Viral oncogene

Front 101

c-onc

Back 101

Cellular oncogene/pro-oncogene

Front 102

How were cellular oncogenes discovered?

Back 102

As part of an oncogenic retrovirus - their names come from the virus (3 letters)

Front 103

What is the role of c-oncs?

Back 103

Regulate cellular growth

Front 104

When are c-oncs expressed?

Back 104

Generally at the beginning of the cells cycle.

Front 105

How do oncogenes exert their effect? (4)

Back 105

1. Products act like GROWTH FACTORS (eg. TGF-beta) - stimulate cells to divide, if over epressed there will be too much growth.

2. Act as GROWTH FACTOR RECEPTORS - stimulate cells to divide.

3. Act as SIGNAL TRANSDUCERS - respond to cell activation by receptor-ligand complexes. (Protein kinase/phosphatase equilibrium disruption can also over enhance signalling).

4. TRANSCRIPTION FACTORS - act directly to increase gene expression.

Front 106

Antioncogenes

Back 106

Normally repress growth,

Front 107

Tumourogenesis - how do oncogenes become disregulated? (3)

Back 107

1. GENE AMPLIFICATION - self perpetuating, changes which confer growth advantages will be selected for.

2. INCREASED EXPRESSION - occurs when the gene is translocated so that it comes under the influence of a strong promoter OR a viral promoter is inserted next to an oncogene.

3. LOSS OF CONTROL FUNCTION - mutation of DNA of oncogene. Oncogene action is controlled by interactions with other proteins/autocatalytic mechanisms which inactivate them - mutations in these will lead to tumourgenesis. (eg. receptor activated even when ligand not present).

Front 108

mutations of oncogenes are?

Back 108

Dominant

Front 109

Mutations of antioncogenes are?

Back 109

Recessive - both alleles must be mutated for cancer to occur.

Front 110

Retinoblastoma

Back 110

develop in homozygotes carrying 2 mutant copies of Rb gene - usually occurs by inheritance of a mutated gene and then one somatic mutation.

Front 111

What to Rb proteins do?

Back 111

Bind to many c-onc products which exert their effect on the nucleus >> prevents c-oncs from increasing transcription.

Front 112

What is the role of p53?

Back 112

Directing the cell towards apoptosis

Front 113

How do mutant p53 genes behave?

Back 113

As dominant oncogenes. however, oncogenic property can be inhibited by overproduction of normal p53.

Front 114

DNA can be damaged by________ to cause cancer.

Back 114

Chemicals - carcinogens, physically, biologically - viruses.

Front 115

Which RNA virus familys cause cancer?

Back 115

Retroviridae, flaviviridae.

Front 116

How do RNA viruses transform cells to cause cancer?

Back 116

changes are mediated directly or indirectly by oncogenes of cellular origin.

Front 117

How do DNA viruses cause cancer?

Back 117

The transforming genes play essential roles in virus growth, transformed genes are true viral genes.

Front 118

In order to induce tansformation what must a virus do?

Back 118

1. express an oncogene as part of its genome
OR
2. Influence the expression of an existing cellular oncogene.

Front 119

What are the characteristics of a cell altered by tumour viruses (5)

Back 119

altered morphology,
increased growth potential
presence of viral DNA,
virus specific tumour associated antigens,
chromosomal abnormalities