Mechanisms of Disease

Question 1

What is the ‘Seed and Soil’ phenomenon?

Answer 1

Malignant cells have a niche environment which they are more likely to spread to. Explains where certain tumours metastasise to.

Question 2

Name 5 cancers that metastasise to bone.

Answer 2

Breast, bronchial, renal, prostate and thyroid.

Question 3

Name some LOCAL effects of neoplasms.

Answer 3

Ulceration, destruction of normal tissue, compression of adjacent structures, blockage of tubes/orifices etc.

Question 4

Name some paraneoplastic effects of neoplasms.

Answer 4

Endocrine effects such as bronchial small cell carcinoma which produces ACTH and ADH or bronchial squamous cell carcinoma can produce PTHrp. The increasing tumour burden also causes a reduction in appetite, cachexia, malaise and immunosuppression.

Question 5

What chemicals can be aetiological factors for neoplasia?

Answer 5

Polycyclic, aromatic hydrocarbons e.g. benzopyrene can cause lung cancer. Aromatic amines e.g. 2-naphylamine can cause bladder cancer. Asbestos is linked to mesothelioma.

Question 6

What are tumour suppressor genes? Give examples.

Answer 6

Genes which slow down cell growth. Require 2 point mutations to cause neoplasia. Examples include p53 and the ‘retinoblastoma (RB)’ checkpoint.

Question 7

What are proto-oncogenes? Give examples.

Answer 7

Enhance growth of cells. Only 1 mutation is required to cause neoplasia. Examples are RAS and HER2.

Question 8

What is xeroderma pigmentosum?

Answer 8

Inheritable cancer syndrome. Nucleotide excision repair is compromised causing susceptibility to UV damage from a young age.

Question 9

What is hereditary non-polyposis colon cancer (HNPCC)?

Answer 9

Inheritable cancer syndrome. Mismatch repair is compromised.

Question 10

What is the adenoma-carcinoma sequence?

Answer 10

Proves that progressive accumulation of mutations forms a malignant neoplasm. Adenoma becomes late adenoma, becomes primary carcinoma becomes metastatic carcinoma.

Question 11

What are the 6 hallmarks of cancer?

Answer 11

Self-sufficiency in growth signalling.
Resistance to stop signals.
No limit to the number of times a cell can divide.
Angiogenesis.
Resistant to apoptosis.
Can invade and produce metastasis,

Question 12

Describe TNM staging.

Answer 12

T refers to the size of the tumour. N is the extent of regional node involvement. M is the extent of distant metastasis.

Question 13

Describe how lymphoma is staged.

Answer 13

Ann-Arbor system.

1: Single node region involved.
2: Multiple node regions involved, on one side of the body.
3: Node regions involved on both sides of the diaphragm.
4: Involvement of extralymphatic organs.

Question 14

Describe the staging of colorectal cancer.

Answer 14

Duke's staging.
A: Invasion into the bowel wall.
B: Invasion through the bowel wall.
C: Lymph node involvement.
D: Distant metastasis.

Question 15

What is tumour grading?

Answer 15

The level of differentiation of the cells. Ranging between well differentiated (G1), moderately differentiated (G2), poorly differentiated (G3) or anaplastic (G4).

Question 16

Describe the grading of breast cancer.

Answer 16

Bloom Richardson scale. Based on tubule formation, nuclear variations and number of mitosis.

Question 17

Name the categories of available chemotherapy drugs.

Answer 17

Antimetabolites - mimic DNA replication substrates.
Alkylating - cross-link DNA so it can’t be transcribed.
Antibiotics - inhibit DNA synthesis enzymes or break DNA double strands.
Plant-derived - block microtubule assembly and mitotic spindle formation.

Question 18

What is imatinib used to treat?

Answer 18

Specifically targets the ‘Philadelphia’ chromosome. Used for some GI stromal tumours and chronic myeloid leukaemia.

Question 19

Name some tumour markers.

Answer 19

Human chorionic gonadotropin (HCG) - testicular tumours and choriocarcinomas.
Alpha-fetoproteins - hepatocellular carcinomas. Carcino-embyronic antigen - colorectal carcinomas.
Cancer antigen 125 - oovarian carcinomas.

Question 20

Give some possible causes of cell injury.

Answer 20

Toxins, physical trauma, radiation, chemical agents, immune mechanisms, hypoxia etc.

Question 21

What are the 4 types of hypoxia?

Answer 21

Hypoxaemic
Anaemic
Ischaemic
Histiocytic

Question 22

What are the 4 main targets for cell injury?

Answer 22

Cell membranes, mitochondria, nuclei and proteins.

Question 23

Describe the cellular processes that occur in reversible hypoxic injury.

Answer 23

Lack of oxygen causes reduced ATP allowing the sodium-potassium ATPase to fail causing cell swelling. Anaerobic respiration increases which decreases pH. Ribosomes begin to detach from the ER so protein synthesis decreases.

Question 24

Describe the cellular processes that occur in irreversible hypoxic injury.

Answer 24

Membrane integrity fails allowing calcium to enter. Calcium increases the activity of ATPase (further reducing ATP stores), phospholipase (worsening membrane integrity), proteases and endonucleases. DNA change is visible.

Question 25

Describe the 2 main types of necrosis.

Answer 25

Coagulative - proteins denature and clump together. A ghost outline can be seen. Most commonly occurs in solid organs such as the heart and kidney.
Liquefactive - enzymes degrade the cells. Occurs in the brain or in tissues where there is a high concentration of neutrophils.

Question 26

Describe caseous necrosis.

Answer 26

Appears as amorphous debris with no outline. Occurs in association with granulomatous inflammation (e.g. in TB).

Question 27

What is gangrene?

Answer 27

The appearance of necrosis to the naked eye. It can be dry gangrene - occurs in dehydrate dead tissue undergoing coagulative necrosis, or wet gangrene - infection and neutrophils present causing liquefactive necrosis.

Question 28

What are the 2 types of infarct?

Answer 28

White - single blood supply so no reperfusion e.g. the heart.
Red - dual blood supply e.g. the lungs.