Cell Injury Adaptation & Death

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adapt

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When they are exposed to extra demands or stress they are designed by nature to adapt in order to preserve the health or wellbeing of the whole body. Such demands may be physiologic, as when the cells and tissues of the uterus adapt to a pregnancy or when the bone marrow responds to a lower oxygen tension of the blood as one ascends to high altitude.

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Hyperplasia

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Hyperplasia is an increase in the number of cells resulting in increased volume of the organ or tissue. It can only be initiated where there is a cell population capable of division and proliferation. It can be physiologic or pathologic.

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Examples of physiologic hyperplasia

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The lactating breast – the increase in number and size of the breast lobules in lactation is due to stimulation by estrogen and the pituitary hormone prolactin (hormonal hyperplasia).

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Examples of pathologic hyperplasia

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Follicular Hyperplasia of Lymph Nodes, for example in the neck in response to an oral infection or dental abscess.

Benign prostatic hyperplasia, a common disorder in men over 50 which is caused by the testosterone metabolite dihydrotestosterone inducing nodular enlargement of the gland.

Squamous hyperplasia: in response to chronic irritation, such as an ill-fitting denture, for example, an irritated area of squamous mucosa may become thickened to compensate for repeated loss of surface epithelial cells

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Hypertrophy

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Hypertrophy is an increase in the size of cells leading to increased tissue volume. The increased size results from increased synthesis of cellular components. Hypertrophy, in contrast to hyperplasia, does not require a cell population capable of cell division but can occur in fully mature non-dividing cells. It also can be physiologic or pathologic and is usually caused by increased functional demand.

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Describe an example of physiologic hypertrophy

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Hypertrophy of hepatocytes due to increased endoplasmic reticulum in response to the functional demand for metabolism of ingested drugs such as Phenobarbital.
Muscle hypertrophy induced by “pumping iron”. The increased size of the individual skeletal muscle fibers is due to increased numbers of actin and myosin fibers and cellular organelles necessary to support increased function, most notably mitochondria.

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Ex. of pathologic hypertrophy

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cardiac muscle hypertrophy in response to abnormally increased peripheral vascular resistance, i.e. hypertension. The mechanism of cardiac hypertrophy involves many signal transduction pathways that lead not only to increased synthesis of functional proteins, but also to the synthesis of growth factors and agents that affect peripheral vessel tone and caliber and even kidney function.

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What is atrophy? What is it driven by?

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Atrophy describes shrinkage of a tissue due to loss of cell substance and or cell number. It can be physiologic or pathologic. An imbalance between protein degradation and synthesis drives the process.

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What's responsible for accelerated proteolysis in atrophy?

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A pathway responsible for accelerated proteolyis in atrophy is referred to as the ubiquitin-proteasome pathway. Targeted proteins are conjugated with ubiquitin which chaperones the protein into a cytoplasmic organelle called a proteasome where it is degraded

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What are autophagic vacuoles?

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atrophic cells can have los of lysosomes with fragments of mito and ER. These are known as autophagic lysosomes

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What cell component is likely to be more numerous in atrophic cells?

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Residual bodies- shruken lysosomes that contain only lipofuschin, a residue of hydrolytic enzyme digestion.

Looks brown in color, so its also called brown atrophy

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Describe an example of atrophy

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Atrophy of disuse- wasting of muscle of limb immobilized by a case. osteoporosis.

Denervation atrophy - interruption of periorpher nerve supply due to trauma.

also ischemia (diminished blood supply)

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Cachecia?

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Atrophy of muscle and internal organs due to inadequate nutrition. Can also be in those with chronic illness and cancer, here you see overproduction of Tumor-necrosis factor.

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What's metaplasia? Why does it occur?

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Reversible change in which one adult cell type is replaced by another adult cell type.

Why does it occur: results from reprogramming of tissue stem cells brought about aby cytokines and GFs (BMP, and TGFbeta can induce undifferentiated mesenchymal cells to differentiate into bone or cartilage)

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Whats the survival benefit of metaplasia?

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Can get greater resistnace to stress or adverse enivornemnt afflicting the tissue.

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What's the most common epithelial metaplasia?

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Converting columnar cells to squamous metaplasa in response to chronic irritation.

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Describe Barrett's esophagus

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Replacement of susceptible squamous mucose of lower esophagus to more acid resistant gastric or intestinal colunar mucosa in response to presistant gastric reflux