Adaptive cell responses

The cell adapts to increased physiological demands or to pathological stimuli by growth alterations leading to several changes in the form of hypertrophy, hyperplasia, atrophy, metaplasia and dysplasia. If the pathology persists then the cell may undergo apoptosis or cell death.

Hyperplasia

It is an increase in the number of cells in an organ or tissue. It may be physiologic or pathological. Physiologic hyperplasia can be seen in response to hormonal stimulus e.g. uterine hyperplasia in pregnancy, or it may be compensatory e.g. hepatic regeneration after partial hepatectomy. Pathological hyperplasia is a result of continued hormonal stimulation causing pathologic conditions like endometrial and prostatic hyperplasia. However, this type of hyperplasia regresses once the hormonal stimulation ceases. Mechanism of hyperplasia is an increase in the number of cells due to increased transcription of growth promoting genes activated by growth factors and hormones.

Hypertrophy

It is an increase in the size of cells leading to an increase in the size of an organ. It may accompany hyperplasia. Typically, cells capable of regeneration, like liver, will respond to injury by hypertrophy and hyperplasia while non-dividing cells like the myocardium, will respond by hypertrophy. It may be physiologic or pathological. Physiologic hypertrophy can be seen in skeletal muscle after weight training and uterus in pregnancy which shows both hypertrophy and hyperplasia. Pathological hypertrophy is seen in the left ventricle in response to long standing hypertension. Mechanism of hypertrophy is increased transcription of genes coding for cellular proteins, transcription factors such as c-fos and c-jun, growth factors like IGF -1, there may be changes in contractile proteins to beta myosin, increased number of cytoplasmic organelles and DNA content. Some embryonic genes may be re-expressed e.g. ANP in the heart.

Atrophy

It is the decrease in size and weight of a tissue or organ due to loss of cell substance and organelles. Physiologic atrophy is seen during embryonic development e.g. in degeneration of notochord or mullerian ducts (in males) and in uterus following pregnancy and childbirth as the uterus reverts back to previous size. Pathological atrophy can follow various causes leading to impaired growth and development which can lead to cell death if persistent. Pathological atrophy is seen in decreased use or workload such as muscle atrophy following prolonged immobilization in a cast; or inadequate nutrition like in marasmus; or loss of hormonal stimulation like atrophy of uterine endometrium and breasts in menopause due to lack of estrogen; or loss of innervation as in LMN palsy; or inadequate blood supply like peripheral vascular disease or sustained pressure like atrophy of the renal cortex and medulla in long-standing hydronephrosis. Ageing is normally accompanied by atrophy, especially in the brain, muscles and heart. Atrophic cells have fewer organelles like mitochondria and endoplasmic reticulum, and show increased protein degradation by cathepsins and acid hydrolases in lysosomes, ubiquitin-proteasome pathway and increase in autophagy. Cellular components contained in the autophagic vacuoles are lysed by lysosomal enzymes. “Brown atrophy” is a normal part of ageing and is seen in organs such as the heart and liver etc. It results from the deposition of yellow-brown lipofuscin and lipochrome pigments as a result of autophagy and lipid peroxidation of membranes.

Metaplasia

It is a reversible change in which one type of adult differentiated cell is replaced by another type of adult differentiated cell. It develops as an adaptation to local stress. The metaplastic epithelium can better withstand stress. Examples are glandular metaplasia of the distal esophagus in GERD called Barrett’s esophagus; intestinal metaplasia in pyloric and antral gastric epithelium and squamous metaplasia of glandular bronchial epithelium in cigarette smoking. Vit A deficiency can cause squamous metaplasia of the respiratory tract. Long-standing metaplasia can predispose to malignancy. Mechanism of metaplasia is the reprogramming of stem cells in response to cytokines , growth factors and hormones induced as a result of the local irritants like acidity or cigarette smoke. Reversal of metaplasia is possible in many cases once exposure to the irritant is stopped.

Dysplasia

It is a pre-neoplastic lesion characterised by disorderly cell growth with some cells showing a lack of maturation, irregular shape and size of cells, cytological features of atypia including enlarged nuclei with prominent nucleoli, increased nuclear to cytoplasm ratio, hyperchromatic, coarse or vesicular chromatin and loss of architecture. Nuclear features of dysplasia can be differentiated from neoplastic cells by the presence of normal mitotic spindles in dysplasia. Dysplasia may be reversible if the initiating factor is removed. Examples of dysplasia are squamous dysplasia of the cervix in response to HPV 16, smoking and squamous dysplasia of the bronchus and squamous dysplasia of the skin due to UV light exposure.