D. Path Week 4: CELLULAR ADAPTATIONS

Cellular adaptations

In response to physiological or pathological stimuli, cells adapt by modifying metabolism (show new steady state) or growth pattern (show structural changes) to better equip them for survival.

Normal Growth - Labile Cells

Constantly divide to replenish those that are lost (i.e. short lifespan, high mitotic rate) e.g. skin, mucous membranes, bone marrow, lymph nodes

Normal Growth - Stable cells

Able to divide but will only do so occasionally (i.e. long lifespan, low mitotic rate) e.g. liver, kidney, glands, smooth muscle.

These cells need to be specially stimulated to divide

Normal Growth - Permanent cells

Permanent cells Have lost/very little ability to divide (i.e. cells need to be maintained for life) e.g. neurones, cardiac muscle, skeletal muscle.

Cells are lost progressively, not replaced by regeneration, no/little mitotic activity

Variations in Growth

- Increased cellular activity (increase in size or number of cells) - Decreased cellular activity (reduction in size or number of cells)

- Alteration of cell morphology (change in cell differentiation)

Hyperplasia

Hyperplasia is the increase in mass of an organ due to an increase in the number of its specialized constituent cells

- Pubertal/lactating breast (physiological)

- Fibroadenosis of breast (pathological)

- Remaining kidney after nephrectomy (compensatory)

- Lymph nodes after infection (reactive)

Hypertrophy

Hypertrophy is the increase in mass of an organ due to an increase in the size of its specialized constituent cells

- Skeletal muscle of athletes (physiological)

- Heart muscle of hypertensive patients (pathological)

Atrpohy

Atrophy is the decrease in mass of an organ due to a decrease in the size and/or number of its specialized constituent cells

The mechanism of decreasing cell size is via increase in catabolism of cytoplasmic structural proteins & removal of organelles by autophagy.

The mechanism of decreasing cell numbers is apoptosis

Physiological atrophy

Physiological atrophy (involution)

Examples:

- Uterus after menopause/childbirth

- Testes in old age

- Thymus gland after childhood

Pathological atrophy

Examples:

- Skeletal muscle in poliomyelitis - motor neuron damage

- Skeletal muscles after immobilisation

- Hydronephrosis due to pressure atrophy caused by urine flow obstruction

- Atrophied brain (elderly patient with dementia)

- Malnutrition (Kwashiorkor) - Dietary deficiency

Agenesis

Failure of an organ to develop at all from its primordia.

Examples:

- Anencephaly (lack of a cerebrum - fatal defect)

- Agenesis of kidney (unilateral or bilateral)

- Amelia (no limbs - thalidomide)

Aplasia

A sudden cessation of growth leading to decreased mass of tissue & defective development of the organ.

Caused by chemo, radiotherapy, nuclear accidents, bomb blasts.

Hypoplasia

Tissue fails to attain full size (deficient growth) leading to decreased mass of tissue & incomplete development of organ.

- Cryptorchidism (maldescended testes causes sterility)

- Microcephaly (hypoplasia of brain causes neurological deficit)

Metaplasia

A fully differentiated adult cell changes into another more resilient but less specialized fully differentiated adult cell type, in response to chronic injury.

Examples:

Smokers resp epithelium changes from stratified to squamous.

Gall stones can cause gallbladder to change from columnar to stratified squamous epithelium.

Dysplasia

An abnormal growth and differentiation with loss of regularity of cells, loss of normal orientation and relationship to one another (i.e. abnormal tissue organisation)

Examples:

- Oral cavity (smoking, ill fitting dentures)

- Respiratory tract (cigarettes)

- Cervix of uterus (HPV)

Hamartoma

A focal overgrowth of normal cells found in a tissue in which these cells ARE usually present (benign tumors)

Choristoma

A focal overgrowth of normal cells found in a tissue, in which these cells are NOT usually present (eg dermatoid cist in ovaries)

Neoplasia

Process which leads to the formation of an abnormal, uncontrolled new growth of tissue, which has no coordinated useful function in the body.

The abnormal mass is called a NEOPLASM (TUMOUR)

3 systems to classify tumours

1) Clinical classification Describes behaviour of tumour and its effect on the patient

2) Histogenetic classification Describes the tissue origin of tumour

3) Morphological classification Describes the appearance of tumour

Benign tumours

- Slow growing, surrounded by CT capsule

- Well supported by abundant stroma

- No infiltration/invasion of normal tissue, do not spread

- Easily treated, good prognosis

Malignant tumours

- Rapidly growing, not encapsulated

- Scanty stroma, fragile blood vessels

- Infiltration and invasion of normal tissue

- May spread to distant parts (metastasis)

- Not as easily treated, usually bad prognosis

Metastasis

The process whereby malignant tumours spread from their site of origin to distant parts of the body forming secondary masses

Primary vs Secondary tumour

Primary tumour: One that is growing at the site of origin

Secondary tumour: One that is growing distant from the site of origin (retaining the histological characteristics of the tissue in which it arose)

Staging of tumours

A "score" is given to indicate the size of a primary tumour, the degree to which it has invaded locally, and how far it has spread - this provides information about clinical behaviour and prognosis

eg. TNM staging system

T refers to size of primary tumour

N refers to lymph node involvement

M refers to extent of metastasis

Differentiating tumours

- Well differentiated (cells RECOGNIZABLE as typical of tissue of origin)

- Poorly differentiated (cells BARELY recognizable as typical of tissue of origin)

- Non differentiated (cells NOT recognizable as typical of tissue of origin - need special stains/immunofluorescence to determine origin)

- Anaplastic tumours (cells are of INDETERMINATE origin)

Histogenic classification

Refers to nomenclature of tumours whereby the name of a tumour provides information about its cell of origin (and whether it is benign or malignant)

Eg: eg. osteoma, adenoma, epithelioma, fibroma

Histogenic classification

Malignant tumours of epithelial tissue origin are given the suffix "carcinoma" e.g. adenocarcinoma, hepatocarcinoma

Malignant tumours of mesenchymal (embryonic connective tissue) tissue origin (support cells & muscle) are given the suffix "sarcoma" e.g. osteosarcoma, fibrosarcoma

Morphological classification

The naked-eye appearance of the tumour or some other physical property is described (palpation findings)

Morphological classification examples

Polyp/polypoid = toadstool like

Papillary (fungating) = cauliflower-like

Ulcerating = excavating, eroding tissue

Infiltrating = rapidly spreading through tissue

Nodular = lump-like

Cystic = cysts filled with fluid

Scirrhous tumour = hard on palpation due to much collagenous stromal tissue

Encephaloid tumour = soft on palpation due to little collagenous stromal tissue