Cell and tissue growth disorders and dysplasia

Question 1

What are the cellular responses to stress and noxious stimuli?

Answer 1

• Cellular adaptation
• Subcellular adaptation
• Cell injury
• Cell death

Question 2

What is hyperplasia?

Answer 2

• Increase in cell number (increase in organ or tissue size)

- Occurs if mitotic division is possible - otherwise hypertrophy

Question 3

When does physiological hyperlasia occur?

Answer 3

• Normal hyperplasia - increased functional capacity of the tissue when needed, eg breast hyperplasia at puberty or pregnancy
• Compensatory hyperplasia - increased tissue mass after damage or partial resection eg unilateral nephrectomy

Question 4

When does pathological hyperplasia occur?

Answer 4

• Hormonal stimulation eg endometrial and prostatic hyperplasia, adrenal cortical hyperplasia in Cushings due to ACTh secreting pituitary adenoma
• Autoimmune phenomenon - Graves
• Wound healing
• Viral wart

Question 5

Why would we get thyroid hyperplasia?

Answer 5

• A lack of secreting tissue (cretinism)
• Lack of substrate (iodine deficiency)
• Lack of enzymes in pathway
• All cause hyperplasia via normal feedback mechanisms - Need TH for bone growth

Question 6

What causes graves?

Answer 6

• TSH autoantibodies

- Causes thyrotoxicosis

Question 7

What is hypertrophy?

Answer 7

• Increased synthesis of structural components, increased cell size (eg myocardial fibres, skeletal muscle fibres)

Question 8

When does physiological hypertrophy occur?

Answer 8

• Increased functional demand eg muscle hypertrophy after regular exercise
• Hormonal stimulation eg myometrial hypertrophy in pregnancy

Question 9

When does pathological hypertrophy occur?

Answer 9

• Increased load placed on organ or tissue eg left ventricular hypertrophy in hypertension or in rheumatic aortic valve
• BPH

Question 10

What are 5 symptoms of BPH?

Answer 10

• obstruction of the outflow tract
• urinary retention
• failure to empty the bladder fully leading to nocturia
• poor flow
• interference with the sphincter
• difficulty starting and stopping micturition, terminal dribbling
• recurrent UTI

Question 11

What is atrophy?

Answer 11

• Reduction in cellular component, decrease in size and number of cells, decreased organ size

Question 12

When does physiological atrophy occur?

Answer 12

• embryological structures undergo atrophy during foetal develop eg thyroglossal duct
• Thymic atrophy at puberty
• Uterus after parturition

Question 13

When does pathological atrophy occur?

Answer 13

• Decreased workload
• Loss of innervation or blood supply
• Compression (lose blood supply)
• Inadequate nutrition
• loss of endocrine stimulation
• Aging

Question 14

What is metaplasia?

Answer 14

• Adaptive substitution of cells by cell types better able to withstand the adverse environment
• Reversible replacement of one mature tissue type by another

Question 15

What are some common examples of metaplasia?

Answer 15

• Squamous metaplasia
• Intestinal metaplasia
• Connective tissue metaplasia

Question 16

Where does squamous metaplasia occur?

Answer 16

Columnar to squamous epithelium (squamous metaplasia)

• respiratory tract due to chronic irritation (bronchus of smokers)
• Stones in excretory ducts eg salivary gland, pancreas, bile ducts
• Endocervix as it everts at puberty

Question 17

Where does intestinal metaplasia occur?

Answer 17

Squamous to columnar

• Barrett’s oesophagus - regular reflux of gastric acid into the oesophagus
• H.pylori infected stomach

Question 18

Where does connective tissue metaplasia occur?

Answer 18

• Myositis ossificans - bone formation in muscle due to injury

Question 19

What is agenesis?

Answer 19

• Complete absence of an organ and its primordium

Question 20

What is aplasia?

Answer 20

• Absence of an organ, but due to incorrect development of primordium

Question 21

What is atresia?

Answer 21

• Absence of opening, usually of a hollow organ eg intestine

Question 22

What is hypoplasia?

Answer 22

• Incomplete development of an organ with decreased number of cells

Question 23

What is dysplasia?

Answer 23

• Abnormal organisation of cells

Question 24

What is heterotopia?

Answer 24

• Well developed tissue but at the wrong site

- eg gastric or pancreatic heterotopia within a Meckel’s diverticulum

Question 25

What is hamartoma?

Answer 25

- Mass of disorganised but mature tissue appropriate to a site - eg bronchial hamartoma is composed of islands of cartilage and respiratory epithelium embedded in smooth muscle and fibrous tissue

Question 26

What is anaplasia?

Answer 26

Lack of differentiation - "hallmark of malignancy"

Question 27

What are some characteristic cytological features of dysplastic and malignant cells?

Answer 27

- Nuclear pleomorphism = variation in shape and size - Nuclear hyperchromatism = variation in darkness of nuclear staining (reflects amount of chromatin) - Increased nuclear:cytoplasmic ration (1:1 or 1:2 rather than normal 1:4) - Increased mitoses visible = often remain in mitotic phase for longer than normal - Atypical mitoses = often have unequal split of chromatin results in aneuploidy

Question 28

When is dysplasia most likely to cause cancer?

Answer 28

- Different levels of dysplasia can occur - mild-moderate-high grade - When it is the full thickness of the tissue = carcinoma in situ - It becomes invasive and very likely to be metastatic when the tumour cells get beyond the basement membrane - Dysplasia isnt necessarily going to progress to cancer, mild/moderate changes may be reversible

Question 29

Give 4 examples of sites that are very likely to become malignant from dysplasia?

Answer 29

- Dysplasia of squamous mucosa in bronchus of smokers - Dysplasia of squamous epithelium of cervical transformation zone in patients with HPV - Dysplasia of Barrett's epithelium in GORD patients - Dysplasia of intestinal epitheium in H.pylori gastritis

Question 30

What can increase the likelihood of developing a cancer?

Answer 30

- genetic disposition - inherited cancer syndromes (germline mutations) can increase risk of developing a malignancy eg retinoblastoma - Non-hereditary predisposition = environment, behaviour, clinical conditions etc

Question 31

Premalignant vs predisposing conditions

Answer 31

- Predisposing (infection of cervix with HPV 16/18, or H pylori gastritis) - give an increase in risk of development - Premalignant - (non-neoplastic disorders with well-defined association with malignancy; high grade dysplasia and ulcerative colitis) - if you have these, you will definitely get cancer

Question 32

What are some characteristics of neoplasms?

Answer 32

- Autonomous growth, not sensitive to feedback mechanisms - DNA mutation in a cell (usually several mutations) confers a survival advantage - DNA mutations are often caused by carcinogens but may arise spontaneously - Monoclonal tumour cell population due to derivation from single cell - mutations in daughter cell may give different characteristics, known as tumour heterogeneity

Question 33

What are stem cells?

Answer 33

- enable tissues to renew themselves, they proliferate and differentiate into mature tissue types - Stem cells have cytoprotective mechanisms which prevent harm from drugs - Not all are locally derived

Question 34

What are cancer stem cells?

Answer 34

- Mutated versions of normal stem cells - Less than 4% of tumour cells can form independently viable clones in culture, the rest die - these immortalised cells are thought to drive tumour growth

Question 35

Why will a mutation cause uncontrolled growth?

Answer 35

- process may be unregulated by the checkpoints - Mutation may affect daughter cells or stem cells, which may continue to drive growth instead of ceasing cell division after differentiation