Tissue growth disorders and dysplasia

Question 1

What are cellular adaptations? + 4 types

Answer 1

Reversible changes in size, number, phenotype, metabolic activity or function in response to changes within their environment

4 types:
Hyperplasia
Hypertrophy
Atrophy
Metaplasia

Question 2

What is hyperplasia? + a requirement
What can happen alongside it?

Answer 2

• Increase in no. cells within affected organ
• Only happens if cell can divide - so cant happen in muscle which has ltd proliferation capacity
• Can happen alongside hypertrophy, in response to the same stimulus

Question 3

Hormonal vs compensatory hyperplasia? egs for each

Answer 3

Hormonal hyperplasia = the need to increase functional capacity of a hormone secreting organ
- eg increase in breast glandular epithelium in puberty/pregnancy

Compensatory hyperplasia = need to increase tissue mass after damage or resection
- eg Liver cell regeneration after donation of one lobe + bone marrow hyperplasia

Question 4

Hypertrophy? - what is it, what its due to, how is it different to hyperplasia

Answer 4

Increase in size of cells which increases size of the affected organ

Due to increase in intracellular structural components

Unlike hyperplasia, happens also in cells unable to divide

Question 5

Describe 2 causes of physiological hypertrophy and how a histological sample of it would look

Answer 5

Due to:
1) Increased FUNCTIONAL DEMAND - eg skeletal muscle fibres in those who gym,

2) HORMONAL STIMULATION of uterus smooth fibres during pregnancy

You would see less nuclei and more cytoplasm

Question 5

4 mechanisms of thyroid hyperplasia?

Answer 5

Lack of substrate – iodine deficiency

Lack of enzymes in thyroid pathway production -> dyshormogenetic

Autoimmune: Grave’s disease – autoantibodies that stimulate or block TSH receptor

Sporadic - usually in females in puberty

Question 6

What is atrophy?
When is physiological atrophy seen + 2 egs of physiological atrophy?

Answer 6

Reduction in size of a structure/organ due to a decrease in cell size and number

Seen in embryological structures during normal development, eg thyroglossal duct

1) Thymus after puberty
2) Uterus after delivery

Question 7

6 examples of pathological atrophy

Answer 7

Decreased workload eg bed rest = skeletal muscle atrophy

Loss of innervation eg skeletal muscle atrophy following spinal cord injury

Diminished blood supply - eg brain atrophy due to atherosclerosis

Inadequate nutrition - Cachexia in chronic inflammation & cancer

Loss of endocrine stimulation - eg endometrial atrophy due to lack of oestrogen after menopause

Pressure - A benign tumour

Question 8

What is metaplasia? + 3 types

Answer 8

Replacement of one differentiated cell type by another in order to withstand an adverse environment

1) Squamous - columnar to squamous (resp tract, excretory ducts)

2) Intestinal/columnar - squamous to columnar (barrett’s oesophagus)

3) Connective tissue - ectopic formation of cartilage, bone or adipose tissue (myositis ossificans)

Question 9

Define Agenesis, Aplasia and Atresia?

Answer 9

Agenesis: complete absence of an organ and its primordium : eg Agenesis of corpus callosum -> neuro-developmental delays

Aplasia: failure of development of the primordium -> absence of an organ
E.g Radial aplasia= failure in radial bone development, causing limb issues. Aplasia can occur as part of broader conditions like VACTERL

Atresia: blockage or absence of an opening, Usually a hollow organ : eg Intestinal atresia= blockage of the intestine–> bowel obstruction

Question 10

Hypoplasia vs Dysplasia? + example for each

Answer 10

Hypoplasia: incomplete development of an organ due to a decreased number of cells
- E.g. Pulmonary hypoplasia due to oligohydramnios

Dysplasia: in context of development – disorganisation of cells
- E.g. Multicystic renal dysplasia due to urinary reflux

Question 11

Heterotopia vs Hamartoma?

Answer 11

Heterotopia:
Well developed nest of normal tissue at the wrong site
E.g. Gastric or pancreatic tissue in a Meckel’s diverticulum -> erosion of cell surface -> bleeding

Hamartoma:
Mass of mature but disorganised tissue at an appropriate site
E.g. Fibrous hamartoma of infancy

Question 12

5 acquired predisposing conditions?

Answer 12

1) Infectious agents
- HPV 16 + 18 (cervical cancer)
- H.pylori (gastric adenocarcinoma)

2) Food and drink (alcohol, diet)

3) Smoking (lung)

4) Reproductive history (breast and ovarian)

5) Environmental carcinogens (UV, IR, asbestos)

Question 13

4 Inherited predisposing conditions?

Answer 13

1) Familial adenomatous polyposis syndrome (APC gene on chromosome 5)

2) Lynch syndrome (mismatch repair genes)

3) Li Fraumeni syndrome (TP53 gene on chromosome 17)

4) Familial breast and ovarian syndrome (BRCA 1 on chromosome 17 or BRCA 2 on chromosome 13)

All AUTOSOMAL DOMINANT

Question 13

Premalignant lesions and conditions

Answer 13

Premalignant lesions:
- High grade dysplasia
- Benign neoplasms at risk of malignant transformations (colonic adenomas)

Premalignant conditions:
- Chronic ulcerative colitis -> colorectal cancer
- Hepatic cirrhosis -> hepatocellular carcinoma

Question 14

Describe cervical screening? (premalignant condition)

Answer 14

Cervical screening:
- Women aged 25 to 64
- First test for presence of HPV – if negative = nothing further done
- If positive = examine cells for dysplasia (dyskaryosis)
- If cytology abnormal = refer for colopscopy and biopsy

• If low-grade dysplasia = no treatment but repeat smear in 12 months as most resolve
• If high-grade = treat w. LLETZ (large loop excision of the transformation zone)

Question 15

Describe how + why we screen individuals w Barrets Oesophagus

Answer 15

• Barrett’s oesophagus can -> invasive oesophageal adenocarcinoma
• Must do regular endoscopies w biopsies every 2cm
• Usually every 2-5 years (time interval depends on length of oesophagus involved)

Question 16

Describe how + why we screen individuals w Familial adenomatous polyposis syndrome

Answer 16

You must do:
- Annual colonoscopies w histology of polyps from 10-15 years until definitive surgery

• Upper endoscopies to screen for gastric & duodenal polyps from time of onset of colonic polyposis or 20 years
• Thyroid ultrasounds due to inc. risk of thyroid cancer
• Provided for first degree relatives for a period defined by findings