Biology Chapter on Cell Growth and Diseases

PATH*3610 Principles of Disease

• This course covers general pathology and the pathology of organ systems.
• It includes topics on cell degeneration and death

Major Principle of Disease

• Definitions are literal and specific
• Use prefixes and suffixes with Latin or Greek meanings.

Disease

• Pathology: The study of suffering; "pathos" (suffering) + "ology" (study of)
• Lesion: A structural change;
• Etiology: The study of the cause
• Pathogenesis: How a lesion develops, mechanisms and lesions.

General Pathology

• Cellular Injury and Adaptation
• Cell Death

Degeneration - Cell Death

• Burn
• Ulcer
• Pus

Stimulus/Insult and Injury

• Outcome of stimulus/injury depends on duration, severity, and physiological state.
• Stimulus can cause reversible adaptations.
• Injury leads to irreversible degeneration or death.

Adaptation to a Stimulus

• Hypertrophy: Increase in cell size.
• Atrophy: Decrease in cell size.

Hyperplasia

• Increase in cell number.
• Labile cells frequently divide (epithelial cells).
• Stable cells can divide (fibroblasts, smooth muscle cells).

Permanent cells (terminally differentiated)

• Neurons, cardiac myocytes, skeletal muscle cells.

Stable cells (resting)

• Fibroblasts, smooth muscle cells, some epithelial cells (kidney, liver).

Labile cells (stem cells)

• Epithelial cells (skin, stomach, intestine)
• Bone marrow progenitors and stem cells

Response vs Healing

• Response of cells includes hyperplasia and hypertrophy
• No response = maintenance.
• Healing of tissue is regeneration or not regeneration.

Principles of Healing by Regeneration

• System: No regeneration in mammals for organs.
• Primary tissue: Regenerative ability varies by tissue type, with supporting tissue (fibrous) generally not regenerative.
• Blood vessels: Usually not regenerative.
• Other cells: Some degree of regeneration possible.
• Cell: Generally capable of regeneration (depending on cell type).

Cell Cycle

• Interphase includes G₀ (resting), G₁ (presynthetic), S (DNA Synthesis), G₂ (premitotic)
• Mitosis (M) involves cell division.

Cell Cycle Regulation

• Growth factors, hormones, and cytokines regulate the cell cycle.
• Some growth factors (GF): epidermal growth factor (EGF), transforming growth factor (TGF), Insulin-like growth factor (IGF), fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF).

Inherent characteristics

• Embryonic stem cells are pluripotent.
• Adult stem cells have a restricted differentiation pattern.

Cell Death – The Terminology Quagmire

• Common terminology includes dead and death.
• Disease terminology includes dead, cell death, tissue death, necrosis.
• Types of death include traumatic death (accidental cell death) and regulated cell death.

Cell Death: The Mechanisms

• Accidental cell death is instantaneous and catastrophic (trauma, freezing, burn, infarct).
• Regulated cell death involves genetic machinery, 12 molecular programs, and initiation/execution phases
• Physiologic cell death is part of normal processes like differentiation and apoptosis (embryological, physiologic, and postembryological).

Cell Death

• About 40 billion cells die each day in the human body.
• Efferocytosis is the silent removal of cell corpses by macrophages.

Cell Death: The Terminology

• Terminology is historical and contextual.
• Descriptors include macroscopic, histological, and molecular pathways/subroutines.

Historical Macroscopic Descriptors of Cell Death

• Coagulative necrosis (dry gangrene): Dead cells appear similar to normal cells
• Liquifactive necrosis: Pus and abscesses
• Caseous necrosis: A form of necrosis characterized by a cheesy appearance.

Ways Cells Die

• Cells can swell (necrosis) or shrink (apoptosis)
• Necrosis: Cell swelling
• Apoptosis: Cell shrinking.

Even More Terminology of Death

• Cell swelling (hydropic cell death/oncotic necrosis)
• Coagulative necrosis (cell does not look different).
• Apoptotic cell death.

Cell Death: Microscopic descriptors

• Swelling: Hydropic cell, fatty change
• Necrosis: Coagulative, liquefactive, caseous, oncotic, gangrene
• Apoptosis: Cell shrinkage and phagocytosis

Cell Death: Yet Another Classification

• Type 1 (apoptotic)
• Type II (autophagic)
• Type III (necrotic).
• Oncotic (swelling).

Cell Death: Mechanisms/Molecular Pathways

• Accidental cell death
• Regulated cell death involves a lethal trigger, genetic machinery, molecular subroutines/programs, initiation/execution phases
• Programmed cell death: Physiological/embryological/postembryological cell death & Differentiation

Degeneration and Death of the Whole Body

• Aging
• Free radicals (reactive oxygen and nitrogen species, RONS).

Death: Growing old gracefully

• Methods to improve aging (e.g., fountain of youth, philosopher's stone, etc.)

Death: Aging theories

• Intrinsic cellular aging (chromosomal shortening, clock genes (nematodes).
• Extrinsic cellular aging (wear and tear, free radicals (RONS)).

Death: Free Radical Injury

• Production vs. scavengers
• Drugs and chemicals
• Inflammation
• Microbial injury
• Irradiation
• Aging

Death: Antioxidants and aging

• Drosophila oxidative pathways
• BMR and aging (higher free radical formation)
• Caloric restriction in various animals, like spiders, guppies, rodents, and dogs.
• Inconclusive in primates.
• Growth hormone - insulin-like growth factor receptor 1 signaling.

Death: Antioxidants

• Natural antioxidants (Vitamin A, C, E, and glutathione).
• Note: While theoretically beneficial, evidence suggests Vitamin E supplements are not effective and may harm.