1.12 Abnormalities Of Growth

Question 1

What is hypertrophy?

Answer 1

Increased growth but no proliferation

Not always pathological, i.e. in skeletal muscle cells after exercise

Question 2

What is hyperplasia?

Answer 2

Increase in cell number (Not always pathological)

Question 3

What is neoplasia?

Answer 3

Growth of tumours

Question 4

What are the two types of decreased growth?

Answer 4

Developmental and progressive

Question 5

What are the three types of increased growth?

Answer 5

Hypertrophy, hyperplasia, neoplasia

Question 6

What is agenesis?

Answer 6

Complete failure to develop during embryonic growth and development due to the absence of primordial tissue, e.g. renal or pulmonary agenesis

Question 7

What is hypoplasia?

Answer 7

This is partial failure to grow or develop, e.g. testes in Klinefelter’s syndrome (47, XXY), ovaries in Turner’s syndrome (45, X)

Question 8

• What is and what is interesting about unilateral pulmonary agenesis?

Answer 8

This is where there is only 1 lung in the chest, but will be extremely well developed and larger than expected.
Surprisingly asymptomatic as overdeveloped organ will compensate. For example, patient shown in PowerPoint was 5 before the missing lung was discovered.

Question 9

How does the remaining/other organ compensate if agenesis/hypoplasia occurs?

Answer 9

The other organ is likely to be hypertrophic to compensate, allowing the condition to often be asymptomatic

Question 10

• How frequent is renal hypoplasia?

Answer 10

~ 1 in 750 live births, often asymptomatic

Question 11

What are the two types of progressive decreased growth?

Answer 11

• Physiological (involution -> shrinkage of organ in old age/when inactive, e.g. thymus at puberty)
• Pathological: general - e.g. cachexia (wasting and weakness of body due to severe chronic illness) - tissue specific - e.g. osteoporosis - and local atrophy

Question 12

What is a function of the thymus?

Answer 12

It is the gland where T lymphocytes are ‘educated’

Question 13

What is involution of the thymus?

Answer 13

This is where the thymus gland shrinks after puberty, slowly decreasing in activity and effectiveness with time (not much contribution past the age of 40). Medulla (where T cells are educated) slowly decreases in mass and is replaced by adipose tissue.

Question 14

Why does the thymus undergo involution?

Answer 14

As immunity is more necessary at a younger age, in order to establish a bank of memory cells - the need for this decreases over time, and so the gland is able to shrink.

Question 15

What is an example of cachexia?

Answer 15

Weight loss in patients with pancreatic cancer - at diagnosis, 85% of patients reported having weight loss, and they were resistant to nutritional support.
Cause: systematic effects of inflammation (linked to cancer)

Question 16

What is osteoporosis?

Answer 16

• A disease where bones are weakened due to cellular components being removed from the matrix within bone tissue by the enzyme trypsin.
• This leaves a higher concentration of osteoclasts to osteoblasts and therefore increased wearing away of trabecular bone.
• Patient more vulnerable to fractures.
• Shown to be linked to a decrease in hormones - oestrogen und women and androgen in men. Particularly frequent in women over the age of 60 as menopause results in lowered oestrogen levels, increasing likelihood of this wastage occurring.

Question 17

• What is a common fracture in the elderly population suffering from osteoporosis?

Answer 17

11th thoracic vertebral fracture, can be caused by falls even from standing height. Bone marrow may be lost in an oedema secondary to the fracture.

Question 18

What could local atrophy be a result of?

Answer 18

• Disuse (e.g. through restriction of movement due to a plaster cast - causes local atrophy of muscle and bone)
• Pressure from a cyst, tumour or aneurysm
• Ischaemia (lack of blood supply) due to vascular disease (no nutrients, therefore cell death occurs)
• Neuropathy (nerve damage, e.g. polio, causes massive neuronal cell death, but 2 out of 3 strains worldwide have been eradicated)
• Idiopathy (unknown cause, e.g. brain atrophy in Parkinsonism)

Question 19

What is the difference between hypertrophy and hyperplasia?

Answer 19

Hypertrophy is increased cell growth, no proliferation.
Hyperplasia is increased cell number, so an increase in proliferation occurs but with balanced growth, so cell size remains similar.

Question 20

What are some features of hypertrophy and hyperplasia?

Answer 20

• They are responses to stimuli external to the organ
• Histology is often normal
• Often provide extra function (e.g. increased RBC number at high altitude in response to prolonged hypoxia/altitude sickness)
• Usually self-limiting, often reversible (will revert if conditions go back to normal)

Question 21

What are some features specific to hypertrophy?

Answer 21

• Characteristic of ‘permanent’ tissues (notably muscles)

* Increase in cell size w/out increase in cell number (no proliferation)

Question 22

What is a physiological example of hypertrophy?

Answer 22

Increase in skeletal muscle mass in response to exercise

Question 23

What is an example of pathological hypertrophy?

Answer 23

Myocardial hypertrophy - may be an adaptive response to pressure or volume stress and is a common response of many forms of heart disease. Difficulty to deliver blood to vessels results in an overcompensation in the form of increased heart muscle mass.

Question 24

What are some features specific to hyperplasia?

Answer 24

Hyper = too much
Plasia = growth
• Typical of renewing tissues
• Increase in cell number whilst retaining mean cell size, ‘balanced’ growth
• Can also be seen in tissues with little obvious renewal

Question 25

What are some physiological examples of hyperplasia?

Answer 25

• Liver regeneration after partial resection
• Increased erythropoiesis at high altitude (incr RBC production, occurs in the bone marrow)
• ‘Resting’ tissues, e.g. endocrine glands like the adrenal glands

Question 26

What is a pathological example of hyperplasia?

Answer 26

Hyperplasia of the thyroid in Grave’s disease, caused by autoimmune antibodies targeting the TSH (thyroid stimulating hormone) receptor, so cells can proliferate resulting in an over-production of thyroid cells and hyperthyroidism.
H&E stain used, number of blue nuclei massively increased in diseased tissue, but organisation of tissue is still vaguely recognisable as thyroid however.

Question 27

• What is the location and function of the thyroid?

Answer 27

Up near the throat, important endocrincyte

Question 28

What is neoplasia?

Answer 28

Growth of tumours, both benign and malignant

Question 29

What are the features of neoplasia?

Answer 29

• Excessive proliferation of one cell type
• Results from cumulative genetic and epigenetic changes, usually clonal
• Cells have abnormal, unbalanced histology
• Cells have no useful function
• Progressive - spontaneous regression (i.e. through immune response activation) is incredibly rare -> new treatments are looking at this however
• Usually arise from a single cell with changes in it’s genome that will then be passed on.

Question 30

• Are epithelial tissues susceptible to becoming neoplastic?

Answer 30

Yes, many epithelial cells have the potential to become neoplastic, so lots of tumours develop from epithelial tissues.

Question 31

What is the nomenclature for benign surface epithelial tumours?

Answer 31

Papilloma

Question 32

What is the nomenclature for malignant surface epithelial tumours?

Answer 32

Carcinoma

Question 33

What is the nomenclature for benign glandular epithelial tumours?

Answer 33

Adenoma

Question 34

What is the nomenclature for malignant glandular epithelial tumours?

Answer 34

Adenocarcinoma

Question 35

Are tumours in mesenchymal tissues common?

Answer 35

No, they are rarer than epithelial tissue cancers.

Question 36

What are some examples of mesenchymal tissue?

Answer 36

Adipocytes and fibroblasts

Question 37

What is the nomenclature for benign mesenchymal cancers?

Answer 37

Based on tissue of origin, e.g. fibroma, lipoma, haemangioma

Question 38

What is the nomenclature for malignant mesenchymal tumours?

Answer 38

Tissue name-sarcoma, e.g. fibrosarcoma

Question 39

What is the nomenclature for haematological cancers of the lymphoid?

Answer 39

Lymphoproliferative disorders, lymphoma

Question 40

What is the nomenclature for benign haematological cancers of bone marrow?

Answer 40

Myelodysplasia

Question 41

What is the nomenclature for malignant haematological cancers of bone marrow?

Answer 41

Leukaemia

CHECK IF THERE ARE BENIGN LEUKAEMIAS

Question 42

Why isn’t there much of a differentiation between benign and malignant cancers in lymphatic cancers?

Answer 42

This is because the terms are more difficult to assign for these diseases - more harmless WBC issues tend to be labelled proliferation disorders.

Question 43

• What are some examples of benign tumours?

Answer 43

• Squamous cell papilloma, aka warts - driven by papilloma virus (which also has links to cervical cancer). Not invasive, polarity of epithelium is still retained but on a larger scale.
• Colorectal adenoma (polyps, glandular) - can be due to an inherited (germline) mutation mutation in the APC tumour suppressor gene (condition: familial adenomatous polyposis coli) when function of the second APC gene is lost by a random mutation. Appears like normal gut tissue that failed to stop growing, in the non-malignant form all of the polyps thankfully remain contained.

Question 44

What are the features of benign tumours?

Answer 44

• Grow by local expansion
• Do NOT invade adjacent tissue, traverse basement membranes or travel to distant sites (metastasise)
• Differentiation usually resembles that seen in normal tissue
• Not always harmless - may cause harm through pressure, secretion of hormones or obstruction
• May progress to malignancy through capacity to obtain additional mutations (increased cell replication)

Question 45

• What are some examples of malignant tumours?

Answer 45

• Papillary thyroid carcinoma (malignant secretory tissue, is invasive) - distinctive huge, misshapen nuclei as detrimental and irregular number of mutations have occurred. Increased protein synthesis and division occurs.
• Squamous cell carcinoma - here, polarity of tissue is lost and nuclei are retained, loss of organisation results in hypoxia which will cause more inflammation, the factors of which feed the tumour. Cells will also necrose.
• Colorectal adenocarcinoma - most likely started off benign (polyps) but once become cancerous it is likely to have already spread invasively, invading muscularis propria, the layer that usually surrounds the polyps. Stratification of normal colon lost.

Question 46

What does H&E staining show in malignant tumours?

Answer 46

Large swathes of blue, indicating a high concentration of nuclei and nucleic acids. Cancerous cells have larger, abnormal nuclei and have increased synthesis of proteins, resulting in more blue being seen than in normal, healthy tissue.

Question 47

What are the features of malignant tumours?

Answer 47

• Growth by invasion of adjacent tissues, can traverse basement membranes and spread to distant sites (metastasise)
• Differentiation is incomplete to some extent (pleomorphism, anaplasia)
• Nuclei are often large, aneuploidic - mitotic abnormalities
• Cause harm through destruction of normal tissue function (may also induce cachexia)

Question 48

What is pleomorphism?

Answer 48

The ability for some organisms to alter their biological function, morphology or reproductive modes in response to the environment. In cancerous cells, this is shown by their variation in size, shape and staining of both the cell and the nucleus and is the first hallmark of a cancerous cell.

Question 49

What is anaplasia?

Answer 49

This is where cells fail to differentiate fully, losing morphological characteristics and mature function - for example, polarity will be lost in epithelial tissues.

Question 50

What are aneuploid nuclei?

Answer 50

This is where cells have/the nuclei contain abnormal numbers of chromosomes, i.e. 45 or 47 in humans

Question 51

What are euploid nuclei?

Answer 51

Cells/nuclei that contain the correct number of chromosomes (i.e. 46 in humans)

Question 52

• What form of hypertrophy occurs whilst men age?

Answer 52

Prostatic hypertrophy - as the prostate increases in size with age, the detrusor muscle of the bladder must also increase in strength so hypertrophies. This hypertrophy of the bladder wall will also occur should the urinary bladder outlet become blocked.