X. How do cells maintain homeostasis and adapt to change?
A. Feedback loops
1. Positive, negative, feedforward regulation
2. Important at cellular and organismal levels
3. at all levels of gene expression from transcription to protein activation and degradation
B. Adaptation, Cell Injury, and Cell Death
1. Lack of homeostasis leads to pathologic adaptations
Examples: hypertrophy, hyperplasia, atrophy, metaplasia, dysplasia, accumulation of intra or extracellular materials
2. More deleterious injuries from decreased essential nutrients and/or oxygen, mutations, etc. result in cell injury.
3. Injury can be reversible or irreversible, the latter leading to cell death by mechanisms of necrosis or apoptosis.
Examples: metabolic alterations, hereditary gene defects, mechanical stress, agonists, growth factors, depletion of ATP, loss of calcium homeostasis, mitochondrial damage, reactive oxygen species, physical and chemical agents and drugs, infectious agents, immunological reactions, nutritional imbalances
4. Injury can result from Inborn errors of metabolism – broad categories
Toxic metabolites
Disease Ex: PKU, galactosemia, urea cycle disorders & ammonia, maple syrup urine, proprionic and methylmalonic academia
Energy deficits
Disease Ex: Glycogen storage disorder (Von Gierke, McArdle), fatty acid oxidation disorders (MCAD), mitochondrial disorders (MELAS, MERRF, Leber hereditary optic neuropathy)
Storage of compounds
Disease Ex: Lysosomal storage - mucopolysacchrides (Hunter, Hurler, San Fillipo); Lysosomal storage – sphinoglipids (Tay-Sachs); Lysosomal storage – glycogen (Pompe); Peroxisomal (Zellweger)
Other IEM
Disease Ex: cholesterol (Smith-Lemli-Opitz, hypertriglyeridemias), copper (Menkes, Wilson)
C. Healing
1. Cell regeneration and repair includes orderly or disorderly cell regeneration, granulation tissue, and fibrosis, and scarring if cell injury is extensive.
2. Control of cell proliferation and growth of tissues
3. Concept of stems cells, differentiation, cell cycle and replication, growth factors, and mechanisms of angiogenesis and collagen deposition
4. Diseases: Neoplasia risk: Barrets esophagus, alcohol, tobacco, succinylacetone (Tyrosinemia I)