Disorders of Growth Flashcards
What is differentiation?
The process by which a less specialized cell becomes a more specialized cell type
What is hyperplasia?
An increase in cell number
Is hyperplasia always pathological?
No, can be physiological
What is hypertrophy?
An increase in cell size
Where does hypertrophy tend to occur?
In muscle: skeletal and cardiac
What is atrophy?
Reduction in cell size and number in an organ that was normal size
What are some of the causes of atrophy?
Ageing
Lack of use/stimulation
What is hypoplasia?
Reduced size of an organ - never fully developed to normal size
Which of the following - hyperplasia, hypertrophy, atrophy and hypoplasia - is not potentially reversible?
Hypoplasia
What is metaplasia?
The replacement of one differentiated cell type with another mature differentiated cell type
Give a clinical example of metaplasia.
Barrett’s oesophagus
What is dysplasia?
Abnormality of development - alteration in size, shape, and organization of adult cells
Which - metaplasia or dysplasia - is pre-malignant?
Dysplasia
What are the three cell types?
Labile cells
Stable cells
Permanent cells
What are labile cells?
Cells that are continuously dividing e.g. surface epithelium
What are stable cells?
Cells with a low level of replicative activity
May divide rapidly when needed - many cells wait in stage G0 of cell cycle for recruitment
e.g. hepatocytes, fibroblasts, endothelium
What are permanent cells?
Non dividing cells that are unable to re-enter the cell cycle
e.g. neurones, skeletal and cardiac muscle cells
Why is regulation of the cell cycle important?
There are many things that could go wrong (e.g. incorrect DNA replication, too much recruitment of cells from G0) that could result in increased proliferation or mutation, leading to disease
What is apoptosis?
Programmed cell death
Is apoptosis always pathological?
No
What are some inducers of apoptosis?
Withdrawal of growth factors Viruses Free radicals Ionising radiation DNA damage Fas ligand/CD95 interaction
Name some disorders in which there is increased apoptosis.
Neurodegenerative disorders
AIDS
Reperfusion injury
Name some disorders in which there is reduced apoptosis.
Neoplasia
Auto-immune disease
What is the Fas ligand/CD95?
A type-II transmembrane protein that belongs to the tumor necrosis factor (TNF) family
Its binding with its receptor induces apoptosis
What is the p53 gene?
A tumour suppressor gene which regulates the cell cycle
What is the Bcl-2 family?
A family of regulator proteins which regulate cell death, by either inducing or inhibiting apoptosis
What is thought to be the major cause of replicative senescence?
Progressive telomere shortening
Why do telomeres get shorter with each DNA replication?
DNA polymerase cannot replicate DNA at the very ends of chromosomes - the telomeres
In which cells is telomerase - the enzyme responsible for maintenance of telomere length - present in?
Germ cells
Stem cells
Cancer cells
What happens to somatic cells when their telomeres become too short?
Growth is arrested - the cells are irreversibly arrested in G0/G1 and lose the ability to respond to growth factors
What is a neoplasm?
An abnormal mass of tissue
Growth exceeds and is uncoordinated with that of the normal tissues
Continues after cessation of the stimuli that evoked the change
What are the characteristics of benign neoplasms?
They resemble normal tissue and are well differentiated They grow by expansion and do not invade other tissues They are encapsulated No necrosis Normal N:C ratio Few mitotic figures Minimal pleomorphism Do not metastasise
What are the characteristics of malignant neoplasms?
Invasive growth pattern Not encapsulated Necrosis common N:C ratio increased Pleomorphic Mitotic figures more frequent/abnormal May metastasise
What name is given to a malignant tumour derived from squamous epithelium?
Squamous carcinoma
What name is given to a malignant tumour derived from glandular epithelium?
Adenocarcinoma
What are the components of a neoplasm?
Neoplastic cells Blood vessels Inflammatory cells - macrophages, lymphocytes, pleomorphs Fibroblasts Stroma
What is the key difference between dysplastic cells and cancer cells?
Dysplastic cells are not invasive
What is the definition of metastasis?
Tumour implants that are discontinuous with the primary lesion - “secondary” tumours
What are some common sites for metastatic disease?
Regional lymph nodes Liver Lung Bone Brain Adrenal gland Skin
Which tumours tend to spread through the lymphatic route?
Carcinoma
Which tumours tend to spread through the haematogenous route?
Sarcoma
Which organs are very effective at arresting circulating cancer cells?
Lung and liver
Does metastatic spread correlate with blood supply?
No
Which cancers are at risk of direct implantation in terms of lymphatic spread?
Mesothelioma
Chondrosarcoma
What are some of the key elements that allow cancer development?
As the tumour progresses: Escape from senescence Evasion of apoptosis Limitless replication potential Angiogenesis Invasion & metastasis
Why might cancer cells exhibit genomic instability?
They have defective DNA repair mechanisms - tumours are more likely to express various mutations
What are the basic two steps of tumour development?
Initiation - electrophilic molecules, DNA damage
Promotion - stimulation of proliferation
How do DNA viruses initiate carcinogenesis?
Do not contain oncogenes - they encode proteins that bind to and inactivate host proteins
How do RNA viruses initiate carcinogenesis?
Contain specific viral oncogenes which are highly homologous to human genes
What are some of the classical oncogenes?
PDGF EGFR ras src myc Bcl2
What are the four ways in which proto-oncogenes can be activated?
Amplification
Translocation
Point mutation (think ras)
Insertional mutagenesis
What type of virus is the human papilloma virus?
DNA virus
How might p53 or other tumour suppressor genes be inactivated?
Point mutation
Deletion
Degradation
Other structural changes
What are some of the characteristics of classical oncogenes?
Stimulate cell proliferation
Inhibit cell death
Are dominant
What are some of the characteristics of tumour suppressors?
Inhibit cell proliferation
Stimulate cell death
Are recessive
