HCR 240: Human Pathophysiology - Week 1: Cell Biology/Altered Cell Biology

Key Terms

  • Physiology: The study of normal biological functions of an organism.

  • Pathology: The study of abnormal or diseased conditions.

  • Pathophysiology: The study of how pathology occurs and what functional physiological changes are associated with the pathology.

Cellular Biology

  • Cells: "Building blocks of life"; the smallest "living" organism.

Types of Cells

  • Prokaryotes

    • Examples: Bacteria, cyanobacteria.

    • Lack organelles; contain a nucleoid instead of a nucleus.

  • Eukaryotes

    • Examples: Higher animals, plants, fungi, and protozoa.

    • Complex cellular organization with organelles and a well-defined nucleus.

  • All human bodily functions depend on the integrity of the cells.

Functions of Eukaryotic Cells

  • Organs are made up of millions of specialized cells.

Eukaryotic Structure and Function

  • Three general components:

    • Organelles: Membrane-bound intracellular "organs."

      • Examples: Nucleus, ribosomes, endoplasmic reticulum, Golgi complex, lysosomes, peroxisomes, mitochondria.

    • Cytoplasm: Semi-fluid cellular filling (cytosol) within the space between the nucleus and the plasma membrane (cytoplasmic matrix).

    • Plasma membrane (plasmalemma): Outer membrane of the cells.

Organelles: Nucleus

  • Functions: Controls cell division and genetic information.

    • DNA (deoxyribonucleic acid)

    • RNA (ribonucleic acid)

  • Nuclear Envelope: A double membrane that covers the nucleus.

  • Nuclear Pores: Gaps in the nuclear envelope that act as gatekeepers for entry and exit.

  • RNA creation from DNA: Transcription

Organelles: Ribosomes

  • RNA-protein complexes created in the nucleus and secreted into the cytoplasm; may float freely or be attached to the endoplasmic reticulum.

  • Functions: Synthesize polypeptides and proteins from RNA.

  • Protein creation from mRNA: Translation

Organelles: Endoplasmic Reticulum

  • Connected to the outer membrane of the nucleus.

  • Rough endoplasmic reticulum: Contains ribosomes; functions to synthesize, fold, and transport proteins.

  • Smooth endoplasmic reticulum: Functions to synthesize lipids and steroid hormones; also acts to remove toxic substances from the cell.

Organelles: Golgi Apparatus

  • Functions: Refine and transport proteins, polynucleotides, and polysaccharide molecules within the cell.

Organelles: Lysosomes and Peroxisomes

  • Lysosome

    • Sac-like organelles filled with enzymes (hydrolases).

    • Functions in intracellular digestion and autophagy.

  • Peroxisome

    • Sac-like organelles filled with enzymes (catalase and urate oxidase).

    • Functions to detoxify waste, break down fatty acids, and synthesize specialized phospholipids.

Organelles: Mitochondria

  • Double membrane organelle responsible for cellular respiration and energy production.

  • Inner membrane contains respiratory chain enzymes which generate adenosine triphosphate (ATP) through oxidative phosphorylation.

  • Mitochondria contain their own DNA that codes for enzymes in the respiratory chain.

  • Oxidative phosphorylation, Electron transport chain, ATP synthase

Cytoplasm

  • Contains cytosol, which makes up 55% of the total cell volume.

  • Site of enzymatic biochemical reactions, contains free ribosomes for protein synthesis, and storage of excess nutrients.

  • The cytoplasm is organized into different compartments by the cytoskeleton, which contains different filaments to maintain cell shape, strength, and movement.

Plasma Membrane

  • Diffusion: Movement of solute molecules from areas of high to low concentration.

  • Osmosis: Movement of water from areas of low solute concentration to high solute concentration.

Plasma Membrane Functions

  • Defines the cell’s boundaries, controls the movement of substances, maintains cell polarity, and plays a role in cell-to-cell communication.

  • Consists of a lipid bilayer, which is permeable to small hydrophobic molecules such as oxygen and carbon dioxide but prevents the diffusion of hydrophilic substances.

  • Water can slowly pass through the membrane or more quickly via aquaporins.

Altered Cellular Biology

Cellular Injury

  • Possible stressors/causes of injury to the cell:

    • Hypoxia

    • Free radicals and reactive oxygen species (ROS)

    • Toxic chemicals

    • Infectious agents

    • Immunological reactions

    • Physical and mechanical factors

    • Genetic factors

    • Nutritional imbalances

Hypoxia

  • Hypoxia – lack of oxygen in cell or tissue

    • Multiple etiologies including lack of oxygen in the air, loss of hemoglobin or hemoglobin function, reduced number of RBCs, respiratory or cardiovascular diseases.

    • The most common cause of hypoxia is ischemia – lack of blood supply

Effects of Oxygen Loss in a Cell

  • Decreased ATP production in the mitochondria.

  • Failure of active transport mechanisms in the cell membrane (Na+/K+ pump).

  • Inability to regulate osmosis (cellular swelling).

  • Detachment of ribosomes from endoplasmic reticulum.

  • Cessation of protein synthesis.

  • Mitochondrial swelling.

  • Leakage of digestive enzymes from lysosomes and autodigestion of intracellular structures.

  • Lysis of plasma membrane.

  • Cell death.

Ischemia-Reperfusion Injury

  • Can occur in tissue transplantations and ischemic syndromes (myocardial, cerebral, hepatic, renal, intestinal, etc.)

  • Secondary injury that results due to the generation of reactive oxygen intermediates (free radicals) within the mitochondria.

  • The mitochondria responds by opening the mitochondrial permeability transport pore, which leads to the massive escape of ATP and solutes, triggering cell death via apoptosis.

Asphyxiation

  • Injury due to failure of cells to receive or use oxygen.

    • Suffocation: Lack of oxygen in the environment or blockage of airways.

    • Strangulation: Compression and closure of the blood vessels and air passages of the neck.

    • Chemical: Carbon monoxide, cyanide.

    • Drowning: Breathing in of fluid instead of O2

Carbon Monoxide Poisoning

  • Carbon monoxide (CO) is a colorless and odorless gas formed in fuels containing carbon such as gasoline, wood, coal, etc.

  • Higher affinity to heme than oxygen; binds to hemoglobin and prevents the transportation of oxygen around the body.

  • This directly reduces the oxygen carrying capacity of blood, which leads to hypoxia.

Free Radicals and Reactive Oxygen Species (ROS)

  • Free radicals are molecules which have lost an electron; they are highly reactive and will bind to proteins, lipids, RNA, and DNA, initiating a chain reaction and causing damage to the cell.

  • Reactive oxygen species (ROS) are naturally formed during mitochondrial respiration; they have important roles in chemical signaling but can lead to pathology when in excess.

Toxic Chemicals

  • Air pollution is the world’s largest environmental health risk.

    • Includes indoor and outdoor air pollution.

    • Increases risk of strokes, heart disease, lung cancer, chronic and acute respiratory diseases (asthma).

    • The Environmental Protection Agencies (EPA) categories 6 air pollutants: carbon monoxide, particle pollution, ozone, sulfur dioxide, nitrogen dioxide, and lead.

Heavy Metal Toxicity

  • Examples: Lead, mercury, arsenic, cadmium

  • Lead poisoning

    • Exposure in children can result in learning/behavior problems, speech/hearing problems, brain/nervous system injury, slowed growth and development.

    • Most common source is paint in older homes (children), the environment (food, water, air), and at work (adults).

    • Toxicity affects central and peripheral nervous systems.

    • Prevention is key.

    • Treatment may include chelation therapy.

    • Need a high index of suspicion, especially in children with behavioral disorders.

Ethanol (alcohol)

  • Results in major nutritional deficiencies (folate, thiamine, magnesium, phosphorous).

  • Metabolism occurs primarily in the liver.

  • Acute alcoholism affects the central nervous system.

  • Chronic alcoholism also affects the liver (fatty liver, alcoholic hepatitis, cirrhosis) and stomach (gastritis).

  • Consumption of alcohol during pregnancy can result in fetal alcohol spectrum disorders.

  • Street drugs: Methamphetamine, marijuana, opioids, etc.

  • Fetal activity of alcohol dehydrogenase (ADH) is <10% of an adult.

Infectious Agents

  • Viruses, bacteria, and parasites can cause injury to cells within the human body.

  • The virulence of an organism depends on its ability to:

    • Invade and destroy cells.

    • Produce toxins.

    • Produce damaging hypersensitivity reactions.

Immunological Reactions

  • Immune-mediated hypersensitivity reactions:

    • Abnormal immune system response to a perceived foreign substance.

    • Examples: Allergies, anaphylaxis, asthma, eczema, etc.

  • Autoimmune disorders:

    • Antibody formation against normal cell receptors; interfere with intercellular communication and cell membrane function.

    • Examples: Thyroid peroxidase antibodies in Graves disease, islet cell antibodies in type 1 diabetes mellitus, acetylcholine receptor antibodies in myasthenia gravis.

Physical and Mechanical Factors

  • Hypothermic injuries: Chilling or freezing of cells.

    • Occurs at body temperatures of <95° Fahrenheit (35° Celsius).

    • Slows metabolic processes, creates electrolyte abnormalities (can lead to cardiac arrhythmias), and produces ROS.

    • Hypothermia protocol is sometimes used in ACLS.

  • In response to heat, your body will: produce sweat (evaporative cooling), vasodilate peripheral blood vessels (surface heat loss).

  • Sweating = vasodilation = Lower blood volume and hemoconcentration of serum, Lower blood pressure, dizziness, fatigue, shock, coma, Hypovolemia protective effect

  • Life-threatening loss of ability to regulate body temperature; body temperature rises uncontrollably

Hyperthermic injuries

  • Injury caused to the cell due to excessive heat.

    • Heat cramps: Cramping of muscles due to loss of salt and water.

    • Heat exhaustion: Hemoconcentration from salt and water loss.

    • Heat stroke: Body temperature >106°F or 41°C; life-threatening vasodilation and hypotension; loss of compensatory thermoregulation.

    • Certain medications/drugs can also disrupt the body’s ability to regulate temperature (malignant hyperthermia, drug-induced hyperthermia, neuroleptic malignant syndrome).

Barometric Injuries

  • Sudden increases or decreases in pressure causing tissue injury.

Ionizing Radiation

  • Capable of removing orbital electrons from atoms; production of free radicals that damage DNA.

Noise

  • Acoustic trauma and noise-induced hearing loss.

Genetic Factors

  • Inherited genetic disorders may alter a cell’s nucleus or plasma membrane structure, shape, receptors, or transport mechanisms.

  • Epigenetic patterning may increase disposition towards cancers, diabetes, and other disorders.

  • Patients with sickle cell disease have an abnormality in the beta-globin subunit in hemoglobin.

Nutritional Imbalances

  • Micronutrients: vitamins, minerals, trace elements, phytochemicals, antioxidants.

  • Macronutrients: carbohydrates, fats, protein.

  • Cells require the appropriate amount of micro and macro nutrients for function.

  • Pathology can occur when there is excessive nutrient intake, deficient nutrient intake, or the body is unable to process the nutrients.

Cellular Adaption

  • Cells respond to stressors and injury through the process of adaption.

  • Main types of cellular "adaption"

    • Atrophy: ↓ cell size

    • Hypertrophy: ↑ cell size

    • Hyperplasia: ↑ cell number

    • Dysplasia: Atypical hyperplasia; not considered a "true" adaption

    • Metaplasia: Replacement of cells with less mature cells of a different type

Atrophy

  • Decrease in cell size; typically also associated with decreased protein synthesis and increased protein catabolism.

    • Physiologic

      • Naturally occurring throughout the aging process

      • Examples: thymus gland atrophies throughout childhood; some brain atrophy occurs naturally as a normal process of aging

    • Pathologic

      • Result of decrease in workload, use, pressure, blood supply, nutrition, hormonal stimulation, and nervous stimulation

      • Examples: Muscle disuse atrophy in paralyzed patients

Hypertrophy

  • Increase in cell size that consequently increases the size of the affected organ.

    • Physiologic

      • Naturally occurring due to increased demand, stimulation by hormones, and growth factors

      • Example: Uterine enlargement during pregnancy

    • Pathologic

      • Result of chronic hemodynamic overload

      • Example: Left ventricular hypertrophy

Hyperplasia

  • Increase in the number of cells due to increased cell division.

    • Physiologic

      • Compensatory (regeneration – hepatic, epidermal, intestinal, bone marrow cells)

      • Hormonal (estrogen dependent organs such as breast and uterus)

    • Pathologic

      • Abnormal proliferation due to excessive hormonal stimulation or effects of growth factors

      • Example: Benign prostatic hyperplasia

Dysplasia

  • Not a true cellular “adaption.”

  • Abnormal changes to cell shape, size, and organization.

  • Sometimes referred to as “abnormal hyperplasia.”

  • Does not necessarily indicate cancer, but can be pre-carcinomic.

Metaplasia

  • Reprogramming of stem cells to replace mature cells with less mature cell of a different type.

  • Example: Replacement of normal bronchial columnar ciliated epithelial cells with stratified squamous epithelial cells.

Cell Death

  • Failure to adapt, or injury that exceeds adaption, may lead to cell death:

    • Apoptosis

      • Regulated or programmed cell death

      • Can occur physiologically or pathologically

      • No inflammatory changes

      • Dysregulated apoptosis can lead to cancer, autoimmune disorders, neurodegenerative disorders, and ischemic injury

    • Necrosis

      • Cellular changes after local cell death and lysis

      • Includes coagulative, liquefactive, caseous, fat, and gangrenous necrosis

      • Inflammatory changes

Assignments

  • See assignments in Canvas

  • Syllabus assignment, Week 1 Worksheet