CELL GROWTH ABNORMALITIES

The cell cycle: A sequence of biochemical or morphological events in the life of a cell. Usually the onset and completion of mitosis (M), and onset and completion of DNA synthesis (S) most frequently used as transition points.

The cell cycle: The onset and completion of mitosis (M), and onset and completion of DNA synthesis (S) most frequently used transition points. The periods between these phases known as gaps (G1 and G2). The time map usually depicted as a cycle, implying that the cells at the begining and end are identical, particularly relevant to stem cells.

The cell cycle Not all cells progress through the cell cycle at the same rate, Most of the variability is observed in the G1 and G2 phases. Other cells may leave the G1 phase and cease progression altogether, enter a quiescent phase, known as GO phase.

S-phase cells In the cycle, during the S-phase cells synthesise DNA, During the the M-phase, two new individual cells are produced. Once a cell is commited to DNA synthesis, mammalian cells will in fact complete mitosis and contribute to cell production.

G1 phase In G1 phase cells decide upon three options: i)re-enter the cell cycle (recycle) ii)enter a quiescent phase (GO phase), from which the cell can return to the cell cycle e.g, proximal renal tubules. iii)To terminally differentiate  lose forever the ability to reproduce.eg. Brain cells (neurons), and cardiac myosites.

Classification of Cells by their proliferation potential. Labile cells: comprise tissues that are in a constant state renewal. e.g. epithelial lining of the GIT, hemopoietic system. Stable cells: tissues that, normally, renewed very slowly but are capable of more rapid renewal after tissue loss. e.g. the liver, and proximal renal tubules.(GO)

proliferation potential iii. Permanent cells: are terminally differentiated and have lost all capacity for regeneration. E.g. neurons, and cardiac myosites.(GO)

Cell cycle progression is controlled by genes. iii. Permanent cells: are terminally differentiated and have lost all capacity for regeneration. E.g. neurons, and cardiac myosites.(Go) Cell cycle progression is controlled by genes. Genes which control cell progression are called oncogenes. Oncogenes code for – growth factors growth factor receptors nuclear transcription factors

oncogenes. Cell cycle progression is controlled by genes. Genes which control cell progression are called oncogenes. Oncogenes code for – growth factors - growth factor receptors - nuclear transcription factors

oncogenes Some oncogenes include: sis gene (PDGF) erb B gene (epidermal growth factor receptor molecule) fos gene jun gene Many tissues respond to pathological conditions by increasing/ reducing cell production

Organs can increase their cell populations through following ways: recruiting cells from the resting G0 pool (liver) shortening the time cells take to complete mitosis (intestine, skin) increasing the number of cells in the cell cycle (intestine, skin)

Psoriasis Example: Psoriasis (skin disease) Normal cells divide every 200 hours  basal layer: 1 layer In psoriasis: cell cycle reduced to < 50 hours  4 basal cell layers

Growth factors: Cells can receive signals/send - to increase proliferation- - to Stop proliferation -to differentiate The signals are small protein or polypeptides molecules called growth factors.

Growth factors include the following: a. Endocrine secretions: cells secrete a hormone directly into a blood vessel;  the hormone then acts on target cells, usually at distant site from source. -Androgen produced in gonads acts on prostate - Estrogen produced gonads, acts on endometrium

. . b. Immune system (Mobile endocrine system) targeted to specific sites as required, produce whole families of cytokines capable of inducing and regressing growth Paracrine secretion One cell produces a cytokine, receptors for the cytokine are located in their neighboring cell. e.g. neuro endocrine cells in GIT

Autocrine loop: The same cell produces growth factor, and has receptors for the growth factor. e.g. oat-cell carcinoma: secrete bombesin have also got receptors for bombesin.

Effect of Growth Factors. Growth factors can exert their effect by combining with receptors on target cells, usually located on cell surface.

Cell Growth abnormalities include: Hyperplasia Hypoplasia Atrophy Hypertrophy Metaplasia Neoplasia

Hyperplasia Def. An increase in the number of cells in a tissue or organ. It is usually associated with an increase in size. Classification: Physiological hyperplasia: e.g. adolescent breast at puberty, pregnancy, lactation. Pathological hyperplasia: e.g. endometrial hyperplasia in perimenopausal women  menstrual irregularities. Compensatory hyperplasia e.g. regeneration of liver after partial resection. Unilateral resection of paired organs (kidney) 

Hypoplasia Def. A decrease in the size of an organ or tissue due to a reduction in cell number. Classification: 1. Congenital e.g. toxoplasmosis brain 2. Physiological e.g. in intestine after prolonged bypass 3. Pathological: disease: lichen sclerosus et atrophicus

Hypertrophy Def. A reversible increase in the size of a cell through an accumulation of increased amount of cell structural components. The true hypertrophic organ has no new cells but only bigger ones. E.g. skeletal muscle hypertrophy due to training.

Classification: Physiological: e.g. growth of uterus during pregnancy (hormonal stimulation) Pathological: e.g. left ventricular hypertrophy in a hypertensive subject

iv. Atrophy Def. A reversible, adaptive response on the part a cell characterised by a decrease in the size and function of the cell or organ.

Causes: reduced functional activity loss of innervation reduced blood supply diminished nutrition loss of hormonal or growth factor stimulation.

Metaplasia Def. Is the conversion of one differentiated cell type to another. Most frequently the sequence is the replacement of a glandular epithelium by a squamous one. Considered to be an adaptive mechanism in response to persistent injury to a cell. Collumnar or cuboidal lining cells commited to differentiated functions, assume a simpler form which offers better protection against the injurous agent.

Dysplasia In normal tissue, e.g. epithelium, the constituent cells exhibit regularity of size, shape and nucleus. Also the cells are arranged in a regular fashion, exemplified by progression from plump basal cells to superficial cells in a squamous epithelium. In dysplasia this monotonous appearance is disturbed by: variation in the size and shape of cells enlargement, irregularity and hyperchromatism of the nuclei disorderly arrangement of the cells within the epithelium

Dysplasia: Dysplasia shares many cytologic similarities with cancer, at times to differentiate the two can be difficult. Dysplasia, is a preneoplastic lesion, i.e. it is a necessary stage in the multi step cellular evolution to cancer.

Neoplasia (New growth

e.g. chronic exposure to tobacco smoke  squamous metaplasia of bronchial epithelium. Metaplasia is reversible if stimulus is removed. Metaplasia can lead to neoplastic transformation. Dysplasia: is an alteration in the size, shape and organization of the cellular components of a tissue.

Classification: