Cell Biology and Signal Transduction

Ligand Binding to Receptors

• Ligands bind to receptors
• Ligand binding can initiate second messengers
• Ligand binding can interact directly with DNA

Growth Factors and Toxins

• Growth factors prevent apoptosis
• Direct-acting toxins disrupt cellular function by binding to critical components or organelles(e.g., mercury)
• Latent toxins are initially benign but become reactive metabolites harming target cells
• Reactive oxygen species (ROS) are highly reactive free radicals damaging cellular components

Cell Damage and Death

• Irreversible cell damage includes the inability to restore mitochondrial function, loss of plasma membrane integrity, and loss of DNA/chromatin structure
• Apoptosis is programmed cell death (controlled) while necrosis is uncontrolled cell death often involving inflammation
• Cell size changes include hypertrophy (increased cell size), hyperplasia (increased cell number), atrophy (decreased cell size), and metaplasia (change in cell type)

Cell Damage and Cancer

• Hyperplasia alone does not cause cancer
• Atrophy can result from decreased workload, loss of innervation, poor blood supply, poor nutrition, or aging
• Metaplasia is seen in smokers' bronchi and Barrett's esophagus
• Dysplasia is disordered cell proliferation
• Ischemia, especially in glucose storage tissues, leads to reliance on glycogen for anaerobic metabolism, producing lactate, lowering pH, and denaturing proteins
• In coagulative necrosis, membrane-bound organelles burst, but the cellular architecture remains intact. Calcium, macrophages, and neutrophils rush in

Types of Necrosis

• Liquefactive necrosis (found in CNS) is characterized by maintaining constant pH, ATP pumps failing, organelle rupture, and active enzymes, resulting in a "moth-eaten" appearance under a microscope.
• Caseous necrosis forms granulomas (e.g., tuberculosis), surrounded by macrophages
• Fat necrosis can be enzymatic (e.g., pancreatic enzymes) or traumatic; it often leads to saponification (making soap from salt and lipids)
• Fibrinoid necrosis is a hypersensitivity reaction in blood vessels
• Eosinophils are often elevated in necrotic bloodwork

Apoptosis Mechanisms

• Intrinsic apoptosis involves mitochondria and is often triggered by embryonic development, lack of external survival signals, or P53 tumor suppressor activity.
• P53 activities include initiating DNA repair, arresting cellular respiration, or inducing BAD under high concentrations
• The BAD pathway involves BAD binding to BCL-2, allowing Bax/Bak to come together, releasing Cytochrome C, and initiating caspase activation for self-destruction.
• Extrinsic apoptosis is triggered by death receptors like TNF-α and Fas/Fas ligand, mainly in the thymus.

Inflammation

• Inflammation's cardinal signs are rubor (redness), calor (heat), tumor (swelling), and dolor (pain)
• Phagocytes and dendritic cells detect pathogens
• Cytokines (inflammation, antiviral interferons, and lymphocyte activators) are released
• Signals flow through the cytoplasm indicating problems. DNA breakdown is a signal.
• The inflammasome recruits leukocytes to respond to danger-associated molecular patterns (DAMPS).
• Inflammation leads to vasodilation and increased vascular permeability, causing exudate (high protein, cellular debris) to flow out of vessels. Transudate (low protein, cellular debris) results from normal blood vessel conditions.
• Histamine release from mast cells is a major driver of vasodilation
• The complement system functions in lysis, inflammation activation, opsonization, and immune clearance
• Cytokines activate endothelial cells for leukocyte adhesion, and chemokines attract leukocytes. TNF blockers (e.g., infliximab, adalimumab, etanercept) treat chronic inflammatory diseases
• Bradykinin is a vasoactive peptide causing vascular permeability and pain.
• Serous inflammation results from injury to serous epithelium, while fibrinous inflammation is a hallmark of chronic inflammation. Ulcers arise from sloughing of inflamed tissue, and granulomatous inflammation occurs when agents can't be eliminated. Septic shock is a massive cytokine response (TNF, IL-1)
• NSAIDs reduce prostaglandins to treat fever. Regenerative capacity depends on cell types' proliferative potential; the liver has regenerative capacity. Scars and macrophages are involved in ECM remodeling, with keloids being excessive ECM production. Persistent inflammation can cause extensive tissue loss and functional impairment (fibrosis).

Causes and Consequences of Cellular Changes and Inflammatory Processes

• Alcohol abuse, diabetes with obesity, and non-alcoholic steatohepatitis can cause fatty liver changes
• Anthracosis, a coal miner's lung, results from exogenous carbon.