Scientific Basis of Medicine: Exam 1

Electrolytes and Acid-Base Balance

Electrolytes

• Electrolytes are minerals that carry an electric charge when dissolved in water
• They have four general functions:
  • Control osmosis of water between fluid compartments
  • Help maintain acid-base balance
  • Carry electrical current, allowing for production of action and graded potentials
  • Serve as cofactors for certain enzymes

Sodium (Na+)

• Most abundant cation in extracellular fluid (ECF)
• Accounts for almost half of the osmolarity of ECF
• Regulated by hormones:
  • Aldosterone
  • Antidiuretic hormone (ADH)
  • Atrial natriuretic peptide (ANP)
• Daily intake of sodium far exceeds recommended daily intake in the American diet

Chloride (Cl-)

• Most prevalent anion in ECF
• Processes that cause increased resorption of Na+ also cause increased resorption of Cl-
• Moves relatively easily between intracellular and extracellular compartments due to Cl- leakage channels and antiporters
• Helps balance the level of anions in different fluid compartments

Potassium (K+)

• Most abundant cation in intracellular fluid (ICF)
• Plays a key role in establishing resting membrane potential and in repolarization phase of action potential in neurons and muscle fibers
• Helps maintain normal intracellular fluid volume
• Regulates pH of body fluids
• Regulated mainly by aldosterone

Bicarbonate (HCO3-)

• Second most prevalent anion in ECF
• Exchange of Cl- for HCO3- maintains correct balance of anions in ECF and ICF
• Regulated by the kidneys
• CO2 increases as blood flows through systemic capillaries, combining with H2O to form carbonic acid, which dissociates to H+ and HCO3-

Calcium (Ca2+)

• 98% stored in skeleton and teeth
• Regulated by parathyroid hormone (PTH) and calcitonin
• Important roles in:
  • Blood clotting
  • Neurotransmitter release
  • Maintenance of muscle tone
  • Excitability of nervous and muscle tissue

Phosphate (PO42-)

• 85% present as calcium phosphate salts in bones and teeth
• 15% ionized, with three important intracellular phosphate ions:
  • H2PO4- (dihydrogen phosphate ion)
  • HPO42- (hydrogen phosphate ion)
  • PO43- (phosphate ion)
• Regulated by PTH and vitamin D (calcitriol)

Magnesium (Mg2+)

• 54% of total body Mg is part of bone matrix
• 46% occurs as magnesium ions
• Important roles in:
  • Normal neuromuscular activity
  • Synaptic transmission
  • Myocardial functions
• Regulated by varying the rate of excretion in the urine

Acid-Base Balance

Properties of Acids and Bases

• Acids and bases react to form salts
• ICF and ECF must contain almost balanced quantities of acids and bases
• pH is a measure of the concentration of H+ ions
• Homeostatic mechanisms maintain the pH of blood between 7.35 and 7.45

Buffer Systems

• Buffer systems maintain constant pH of fluids inside and outside the cell
• Convert strong acids or bases to weak acids or bases
• Important buffer systems:
  • Carbonic acid-bicarbonate buffer system
  • Protein buffer system
  • Phosphate buffer system

Lung Regulation of Blood pH

• Changes in the rate and depth of breathing can alter the pH of body fluids
• Increased ventilation – more CO2 exhaled – blood pH increases
• Decreased ventilation – less CO2 exhaled – blood pH decreases

Kidney Regulation of Blood pH

• Kidneys excrete H+ and reabsorb HCO3- to regulate blood pH
• Phosphate buffer system helps buffer excess H+ in the urine

Acid-Base Imbalances

• Acidosis – blood pH less than 7.35
• Alkalosis – blood pH greater than 7.45
• Compensatory mechanisms:
  • Respiratory system can compensate for metabolic causes
  • Kidneys can compensate for respiratory causes

Basic Lab Findings with Acid-Base Imbalance

• Look at 3 factors of arterial blood sample (ABG):
  • pH
  • pCO2
  • HCO3-
• Decide if the cause is a change in pCO2 (respiratory) or HCO3- (metabolic)

Cell Injury and Death

• Etiology: The study of underlying causes and modifying factors that contribute to the initiation and progression of disease.
• Pathogenesis: The mechanisms of disease development and progression, which account for all changes that characterize a specific disease.
• Cell Injury: A variety of changes that a cell suffers due to external and internal environmental changes, which can be reversible or irreversible.
• Cell Death: The event of a cell ceasing to carry out its functions, which can occur through apoptosis, necrosis, or autophagy.

Cell Adaptation

• Cell Adaptation: A process in which cells achieve a new steady state and preserve cell function in response to physiologic stress or potential injury.
• Cell Injury and Death: Crucial events in the evolution of disease in any organ or tissue.

Causes of Cell Injury

• Hypoxia and Ischemia: Oxygen deficiency and reduced blood supply, which can lead to cell death.
• Infectious Agents: Viruses, bacteria, fungi, and protozoans can cause cell injury.
• Genetic Abnormalities: Can cause cell injury due to deficiency of functional proteins or accumulation of damaged DNA.
• Immunologic Reactions: Incidental damage to cells or tissues as the immune system defends against pathogenic microbes, auto-immune reactions, or allergic reactions.
• Physical Agents: Trauma, extremes of temperature, radiation, electric shock, and sudden changes in atmospheric pressure.
• Chemical Agents: Toxins, air pollutants, insecticides, carbon monoxide, asbestos, cigarette smoke, ethanol, and therapeutic drugs.
• Nutritional Imbalances: Protein-calorie deficiency, vitamin deficiencies, and excessive dietary intake.
• Aging: Cellular senescence results in a diminished ability of cells to respond to stress and eventually leads to cell death.

Reversible Cell Injury

• Stage of Cell Injury: Abnormal function and morphology of the injured cells can return to normal if the damaging stimulus is removed.
• Morphological Changes: Cellular swelling and fatty change are two main morphological changes associated with reversible cell injury.

Cell Death

• Necrosis: Accidental cell death due to severe damage, characterized by cellular constituents failing or falling apart, and eliciting a local host reaction (inflammation).
• Types of Necrosis: Coagulative, liquefactive, gangrenous, caseous, fat, and fibrinoid.
• Apoptosis: Programmed cell death, characterized by the activation of enzymes that degrade nuclear DNA and nuclear and cytoplasmic proteins, and occurs through the mitochondrial (intrinsic) pathway or death receptor (extrinsic) pathway.
• Autophagy: A survival mechanism in which cells digest their own components during times of nutrient deprivation, allowing cells to live by recycling nutrients and energy.

Clearance of Apoptotic Cells

• Phagocytosis: Macrophages clear apoptotic cells, facilitating prompt removal of dead cells before they release their contents and induce inflammation.

Mechanisms of Cell Injury and Death

• Cellular Response to Injurious Stimuli: Depends on the type, duration, and severity of the injury, as well as the type, status, adaptability, and genetic makeup of the injured cell.### Cellular Injury
• Skeletal muscle can tolerate ischemia for 2-3 hours without reversible injury, but cardiac muscle can only tolerate 20-30 minutes.
• Genetic variations can contribute to differences in responses or pathways and lead to different outcomes.
• Cell injury usually results from functional and biochemical abnormalities in one or more of a limited number of essential cellular components.
• Different external insults or internal disruptions affect different cellular organelles and lead to different responses.

Hypoxia and Ischemia

• Deficiency of oxygen leads to failure of many energy-dependent metabolic pathways and leads to necrosis.
• One of the most frequent causes of cell injury and necrosis in clinical medicine.
• Cells that are subjected to hypoxia that do not immediately die, activate compensatory mechanisms.
• Persistent or severe hypoxia/ischemia leads to failure of ATP generation and depletion of ATP in cells.

Ischemia-Reperfusion Injury

• Restoration of blood flow to ischemic but viable tissue can actually result in cell injury.
• New damage may be initiated during reoxygenation by increased generation of reactive oxygen species (ROS).
• Inflammation from ischemic injury may increase with reperfusion.

Oxidative Stress

• Refers to cellular abnormalities induced by reactive oxygen species (ROS).
• ROS are chemical species with a single unpaired electron in an outer orbit.
• ROS readily react with inorganic and organic molecules, avidly attack nucleic acids, and initiate reactions that convert molecules into other types of free radicals.

Removal of Reactive Oxygen Species

• Cells have mechanisms to remove free radicals and minimize injurious effects.
• Enzymatic and non-enzymatic systems serve to inactivate free radicals.
• Examples of antioxidants include superoxide dismutase, glutathione peroxidases, catalase, and vitamins A, E, C, and beta-carotene.

Cell Injury

• Toxins, including environmental chemicals and substances produced by infectious pathogens, induce cell injury that results primarily in necrotic cell death.
• Latent toxins are converted to reactive metabolites, which then act on target cells.
• DNA damage triggers apoptotic death.
• Inflammation elicited by pathogens, necrotic cells, and dysregulated immune responses can also lead to cell injury.

Cellular Stress and Misfolded Proteins

• Accumulation of misfolded proteins in a cell can stress compensatory pathways in the ER and lead to apoptosis.
• Misfolded proteins can result from abnormalities that increase production of misfolded proteins and reduce the ability to eliminate them.
• Examples of diseases associated with protein misfolding include neurodegenerative diseases such as Alzheimer's, Huntington's, and Parkinson's.

Intracellular Accumulations

• Cells may accumulate abnormal amounts of various substances, which can be harmless or cause varying degrees of injury.
• Examples of intracellular accumulations include fatty change (steatosis), cholesterol, proteins, glycogen, pigments, and pathologic calcifications.

Cell Transport Mechanisms

• There are two main types of cell transport mechanisms: passive transport and active transport.
• Passive transport does not use energy from the cell, whereas active transport uses energy from the cell.

Passive Transport

• Diffusion is a type of passive transport that occurs when there is a random mixing of particles in a solution.
• The rate of diffusion is influenced by:
  • Steepness of concentration gradient
  • Temperature
  • Mass of diffusing substance
  • Surface area
  • Diffusion distance
• Simple diffusion occurs when solutes move freely through the lipid bilayer without the help of membrane transport proteins.
• Examples of substances that move through simple diffusion include:
  • O2, CO2, and nitrogen gases
  • Fatty acids
  • Steroids
  • Fat-soluble vitamins (A, D, E, and K)
• Small, uncharged molecules can also pass through simple diffusion.
• Facilitated diffusion occurs when a membrane channel or carrier assists a substance in crossing the membrane.
• Channel-mediated facilitated diffusion moves solutes through a membrane channel down a concentration gradient.
• Carrier-mediated facilitated diffusion uses a carrier protein to move solutes across the membrane.

Active Transport

• Primary active transport uses energy from the hydrolysis of ATP to ADP to pump solutes across the membrane.
• Examples of primary active transport include:
  • Na/K ATPase pump
• Secondary active transport uses energy stored in ionic electrochemical gradients to drive solutes across the membrane.
• Vesicular transport includes:
  • Endocytosis
  • Receptor-mediated endocytosis
  • Phagocytosis
  • Bulk-phase endocytosis
  • Exocytosis

Osmosis

• Osmosis is a type of passive transport that occurs when there is a net movement of a solvent through a selectively permeable membrane.
• In living systems, the solvent is water.
• Water moves from an area of higher water concentration and lower solute concentration to an area of lower water concentration and higher solute concentration.
• Osmosis occurs only when the membrane is permeable to water but not to certain solutes.
• Equilibrium occurs when the rate of water movement from one side to the other is equal to the rate of water movement from the other side to the first side.

Fluid Balance and Electrolyte Balance

• Fluid balance and electrolyte balance are closely related.
• The kidney plays a huge role in maintaining homeostasis by adapting excretion based on variations in intake.
• The body gains water through:
  • Ingestion
  • Metabolic water production
• The body loses water through:
  • Kidney excretion
  • Skin evaporation
  • Lungs
  • GI tract
  • Menstrual flow

Body Fluid Compartments

• The body has two main fluid compartments:
  • Intracellular fluid (ICF)
  • Extracellular fluid (ECF)
• The ECF is further divided into:
  • Interstitial fluid
  • Plasma
  • Lymph
  • CSF
  • Synovial fluid
  • Aqueous and vitreous humor
  • Fluid in the GI and urinary tracts
  • Serous fluid

Potential Spaces

• A potential space is a space that can occur between two adjacent structures that are normally pressed together.
• Examples of potential spaces include:
  • Pleural cavity
  • Pericardial cavity
  • Peritoneal cavity
  • Synovial cavities
  • Epidural space
  • Retropharyngeal space
  • Between fascial planes

Osmolarity and Osmolality

• Osmolarity is a measure of the total number of dissolved particles in 1L of a solution.
• Osmolality is a measure of the number of solutes per kg of water.
• Iso-osmotic solutions have the same osmolarity.
• Hyper-osmotic solutions have a higher osmolarity than the surrounding solution.
• Hypo-osmotic solutions have a lower osmolarity than the surrounding solution.

Tonicit

• Tonicity is the ability of a solution to modify the volume of cells by altering their water content.
• Tonicity is determined by the concentration of non-penetrating solutes in a solution.
• Isotonic solutions have the same concentration of non-penetrating solutes as the ICF.
• Hypotonic solutions have a lower concentration of non-penetrating solutes than the ICF.
• Hypertonic solutions have a higher concentration of non-penetrating solutes than the ICF.

Dehydration

• Dehydration occurs when the body loses more water than it takes in.
• Dehydration can lead to a decrease in blood volume and a decrease in blood pressure.
• The body responds to dehydration by:
  • Increasing thirst
  • Increasing water intake
  • Increasing ADH release
  • Increasing water reabsorption in the kidneys

Balance of Renal Sodium Absorption

• The kidney regulates the amount of sodium in the body by controlling the amount of sodium excreted in the urine.
• Hormones that regulate renal sodium absorption include:
  • Aldosterone
  • Atrial natriuretic peptide (ANP)### Factors Affecting Membrane Transport
• Increased solute concentration increases solute's osmotic pressure, making it harder to cross the membrane
• Charged or polar solutes that cannot cross the membrane via passive transport require active transport, which needs energy from the cell

Active Transport

• Exhibits specificity, affinity, saturation, and competition
• Solutes that use active transport can cross the membrane via facilitated diffusion if the correct channel or carrier is present
• Examples of solutes that use active transport: Na+, K+, Ca2+, H+, I- (iodide), Cl-, amino acids, and monosaccharides

Primary Active Transport

• The most prevalent carrier is the Na+/K+ pump (also known as Na+/K+ ATPase pump)
• The Na+/K+ pump maintains a low concentration of Na+ inside the cell by pumping it out to the extracellular fluid (ECF) and a high concentration of K+ inside the cell by pumping it in
• K+ and Na+ slowly leak across the membrane, so the Na+/K+ pump is working continuously

Secondary Active Transport

• Energy stored in the ionic electrochemical gradient is used to drive other solutes across the membrane against their own concentration or electrochemical gradient
• Most secondary transport is driven by the Na+ electrochemical gradient, established by primary active transport
• Secondary transport uses energy from the hydrolysis of ATP indirectly
• The Na+/K+ pump maintains a steep concentration gradient of Na across the membrane, which is harnessed to drive other solutes across the membrane
• Carrier proteins bind to Na+ and another solute, changing shape to transport both solutes simultaneously
• Symporters: transporter that moves two solutes in the same direction
• Antiporters: transporter that moves two solutes in opposite directions

Vesicular Transport

• Vesicles (small membranous sac) are used to move substances across membranes
• Types of vesicular transport:
  • Endocytosis: material moves into a cell in a vesicle formed from the plasma membrane
  • Exocytosis: material moves out of the cell by fusion of vesicles inside the cell with the plasma membrane
  • Transcytosis: vesicles undergo endocytosis on one side of the cell, move across the cell, and then undergo exocytosis on the opposite side
  • Transepithelial: movement of solutes across epithelial cells
  • Secretion: movement of solutes from the bloodstream into the lumen of an organ

Endocytosis

• Bulk-Phase Endocytosis (Pinocytosis): all solutes dissolved in the ECF are brought into the cell
• Receptor-mediated Endocytosis: highly selective, receptor protein in the plasma membrane binds to specific solutes
• Phagocytosis: bulk uptake of large particles or cells by the cell

Acute Inflammation

• Acute inflammation causes dilation of arterioles and increases permeability of venules.
• Various stimuli/mediators trigger release of arachidonic acid from polymorphonuclear (PMN) cells.
• Fibrinous exudate develops when vascular leaks are large, and shed cells are poor in fluid.
• Serous exudate is a cell-poor fluid that leaks and has high molecular weight proteins.
• Purulent inflammation involves the production of pus, consisting of neutrophils, liquefied debris, and fluid.

Patterns of Acute Inflammation

• Fibrinous inflammation: exudate develops when vascular leaks are large, and shed cells are poor in fluid.
• Purulent inflammation: involves the production of pus, consisting of neutrophils, liquefied debris, and fluid.
• Ulceration: a local defect or excavation of the surface of an organ/tissue, produced by necrotic tissue and inflammation.

Removal of Agent

• Leukocytes eliminate microbes and dead cells by phagocytosis, followed by destruction in phagolysosomes.
• Destruction is caused by free radicals (ROS, NO) generated in activated leukocytes and by granule enzymes.
• Neutrophils can extrude their nuclear contents to form extracellular nets that trap and destroy microbes.
• Granule enzymes may be released into the extracellular environment and cause damage.

Regulation of the Response

• Inflammation declines after offending agents are removed.
• Reaction resolves because mediators are broken down and dissipated.
• Leukocytes have short life spans in tissues.
• After the goal of eliminating offending agents is achieved, the process of tissue repair is set in motion.

Repair

• Two options: regeneration or repair by laying down connective tissue.
• Regeneration: some tissues are able to replace damaged components and essentially return to a normal state.
• Repair by laying down connective tissue: scar formation is not normal.

Hemostasis and Inflammation

• Hemostatic plug of platelets formed – stops bleeding and provides a scaffold for infiltrating inflammatory cells.
• Inflammation: typical acute and chronic inflammatory responses.

Systemic Effects of Inflammation

• Fever: pyrogens induce fever, and prostaglandins produced in the vascular and perivascular cells of the hypothalamus increase body temperature.
• Acute-phase proteins: plasma proteins synthesized by the liver, stimulated by cytokines.
• Leukocytosis: cytokines stimulate production of leukocytes from precursors in the bone marrow.

Wound Healing

• Healing by first intention: healing of a wound that has opposed edges (primary union).
• Healing by secondary intention: healing of a wound with separated edges (secondary union).

Factors that Impair Tissue Repair

• Infection: prolongs inflammation and potentially increases local tissue injury.
• Diabetes: compromises tissue repair for many reasons.
• Nutritional status: protein malnutrition and vitamin C deficiency inhibit collagen synthesis and slow healing.
• Glucocorticoids: may result in weak scars.
• Mechanical factors: may cause wounds to pull apart.
• Foreign bodies: fragments of steel, glass, bone, and other materials impede healing.

Abnormal Wound Healing

• Chronic wounds: venous leg ulcers, arterial ulcers, pressure sores, and diabetic ulcers.
• Excessive scarring: hypertrophic scars, keloid, exuberant granulation, and contracture.

Cellular Metabolism

• Metabolism consists of all chemical reactions that occur in the body, including catabolism (breakdown of molecules) and anabolism (synthesis of molecules)
• Catabolic reactions release energy, while anabolic reactions absorb energy
• Activation energy is required to start a chemical reaction, and it can be lowered by enzymes
• ATP (adenosine triphosphate) is the energy currency of the body, generated through two mechanisms: substrate-level phosphorylation and oxidative phosphorylation
• Cellular respiration is the cornerstone of metabolism, where energy-producing nutrients (mainly glucose) are catabolized to release ATP

Enzyme-Substrate Interaction

• Enzymes are protein molecules that catalyze chemical reactions, accelerating the conversion of reactants into products
• Enzymes are highly specific, efficient, and subject to various controls
• Substrate is the reactant molecule on which an enzyme acts
• Enzyme-catalyzed reaction rate is influenced by factors such as temperature, pH, substrate concentration, and activators or inhibitors
• Enzyme-substrate interaction involves binding of the substrate to the active site, where it is transformed into products through rearrangement, breakdown, or combination of substrate molecules

Cell Signaling

• Cell signaling is the communication between cells to coordinate activities
• Cell-to-cell communication uses three methods: gap junctions, cell-to-cell binding, and extracellular chemical messengers
• Gap junctions allow ions and small molecules to diffuse between neighboring cells
• Cell-to-cell binding involves the interaction of surface molecules on adjacent cells
• Extracellular chemical messengers (ECM) bind to receptors, triggering signal transduction and cellular response

Extracellular Chemical Messengers (ECM)

• ECM types include hormones, neurotransmitters, and local mediators
• Hormones are carried by the blood to distant target cells
• Local mediators act on nearby target cells without entering the bloodstream
• Examples of local mediators include cytokines, nitric oxide, and eicosanoids
• Eicosanoids are synthesized from membrane phospholipids and have various roles in promoting inflammation, fever, and intensifying pain

Receptors

• Receptors detect signal molecules and initiate signal processes
• Receptor binding exhibits specificity, affinity, saturation, and competition
• Agonists bind to and activate receptors, while antagonists bind to and block receptors
• Receptor location can be on the plasma membrane (for water-soluble ECM) or inside the target cell (for lipid-soluble ECM)
• Receptors are subject to regulation, including up-regulation and down-regulation

Signal Transduction Pathways

• Signal transduction pathways involve a sequence of events between ECM binding and cellular response
• In many signaling pathways, a series of relay proteins conveys the signal between receptor and effector protein
• Intracellular messengers are generated to help mediate the transduction process

Plasma Membrane Receptors

• Four types of plasma membrane receptors: G-protein-coupled receptors, ligand-gated ion channels, receptor tyrosine kinases, and nuclear receptors
• G-protein-coupled receptors are the largest family of plasma membrane receptors, with a messenger binding site, transmembrane segment, and site coupled to a G-protein

Membrane Permeability and Gradients

• Plasma membranes are selectively permeable, allowing some substances to pass through while blocking others
• Membrane permeability increases with more hydrophobic or lipid-soluble substances
• Concentration gradients and electrical gradients drive the movement of substances across membranes
• Electrochemical gradients are the combined influence of concentration and electrical gradients, driving the movement of ions

Cell Adhesions

• Cell adhesions are types of cell junctions, including adherens junctions, tight junctions, and desmosomes
• Adherens junctions are dense layers of proteins on the inside of the plasma membrane, involved in cell-cell adhesion
• Tight junctions seal off passageways between adjacent cells, found in epithelial tissues that line organs such as the stomach and intestines

Cancer and Metals

• Benzopyrene, found in cigarette smoke, is metabolized to an intermediate that binds to DNA, leading to lung and bladder cancer.
• Lead, used in batteries and ammunition, is a metal that can cause acute and chronic toxicity, carcinogenicity, and intellectual impairment.

Lead Exposure

• Industrial exposure to lead occurs through inhalation in workplaces such as mining and manufacturing.
• Lead accumulates in bones and developing teeth, and can be absorbed through ingestion of contaminated food and beverages.
• Lead is rapidly cleared from the blood, but levels can remain high in the body due to accumulation in bones.
• Intestinal absorption of lead is enhanced by calcium, iron, or zinc deficiency.

Toxicity and Effects of Metals

• Mercury is known to cause renal toxicity, tremors, dementia, cerebral palsy, and mental retardation.
• Cadmium, used in paint pigments, alloys, electroplating, and batteries, is a toxic metal.
• Arsenic, a risk factor for miners, smelters, oil, and farm workers, increases the risk of lung, skin, and liver cancer.

Injuries and Hazards

• Agricultural injuries include skin injuries (abrasions, lacerations, contusions), bone injuries, and head injuries.
• Heat-related illnesses include heat cramps, heat exhaustion, and heat stroke, caused by prolonged exposure to high temperatures and humidity.

Thermal Injuries

• Hypothermia occurs when the body temperature drops below 90°F, leading to loss of consciousness, bradycardia, and atrial fibrillation.
• Trench foot is caused by vasoconstriction and increased permeability from slowly falling temperatures, leading to edematous changes.
• Frostbite is caused by ischemia that results from sudden and persistent falls in temperature.

Burns

• Partial thickness burns are characterized by pink or mottled skin with blisters and are painful.
• Full thickness burns are white or charred, dry, and without feeling, and can lead to systemic consequences such as neurogenic and hypovolemic shock, infection, and hypermetabolic state.

Electrical Injuries

• Electric current can cause sudden death by disrupting neural regulatory impulses, producing cardiac arrest.
• Thermal injury to organs can occur when electric current flows through the body, and the most important variables are the resistance of tissues to the conductance of the electric current and the intensity of the current.

Other Injuries

• High-altitude illness occurs at altitudes above 4000m, causing progressive mental obtundation and cerebral and pulmonary edema.
• Blast injury occurs due to violent increases in pressure, either in the atmosphere or in water.
• Air or gas embolism can occur as a complication of scuba diving, mechanical positive-pressure ventilatory support, and hyperbaric oxygen therapy, and can lead to pulmonary, mediastinal, and subcutaneous emphysema.
• Acoustic trauma can cause permanent hearing loss and tinnitus due to loud noise exposure.

Cellular Biology Basics

• Involuntary Muscle: attached to bones of the skeleton
• Smooth Muscle: located in the walls of hollow internal structures (blood vessels, airway to lungs, stomach, intestines, and urinary bladder)
• Cardiac Muscle: forms the bulk of the heart wall

Nervous Tissue

• Detects changes in the body's external or internal environment and elicits an appropriate response
• 2 Types of Cells:
  • Neurons: sensitive to a variety of stimuli, convert stimuli to electrical signals (Action Potential), or “nerve impulses”
  • Neuroglia: do not conduct action potentials, but have many other important, supportive functions
• 3 Basic Parts of a Neuron:
  • Cell Body: contains the nucleus and other organelles
  • Dendrite: short, branched processes that are the major receiving or input portion of a neuron
  • Axon: single, thin, cylindrical process that may be very long, it is the output portion of a neuron

Levels of Organization of the Body

• Chemical
• Cellular
• Tissue
• Organ
• System
• Organismal

12 Organ Systems

• Nervous
• Muscular
• Skeletal
• Endocrine
• Cardiovascular
• Immune
• Lymphatic
• Integumentary
• Respiratory
• Urinary
• Digestive
• Reproductive

6 Most Important Life Processes of the Human Body

• Responsiveness
• Movement
• Growth
• Differentiation
• Reproduction
• Metabolism

4 Key Themes of Physiology

• Homeostasis
• Integration
• Mechanism of Action
• Communication

Feedback Loops

• Negative Feedback Loop: occurs when a change in a variable triggers a response that reverses the initial change
• Positive Feedback Loop: occurs when a change in a variable triggers a response that causes more change in the same direction

Chemical Components of the Body

• Major elements of the body: carbon, hydrogen, oxygen, nitrogen (96% of composition)
• Inorganic molecules: generally do not have carbon, simple
• Organic molecules: made up of carbon (chains)
• Examples:
  • DNA
  • Glucose
  • Water
  • ATP

Prokaryotic vs. Eukaryotic cells

• Prokaryotic:
  • Single-celled organisms
  • Bacteria (rRNA)
  • No membrane-bound nucleus or organelles
  • No mitochondria
  • Circular strands of DNA
  • Extremely small
• Eukaryotic:
  • Can be single-celled or multi-celled
  • Fungi, protists, plants, and animals
  • Contain nucleus and organelles bound by plasma membrane
  • Double-stranded, linear DNA

Cell Components

• Plasma Membrane: flexible outer surface, separates internal from external environment, regulates flow of material into and out of the cell
• Cytoplasm: consists of all cellular contents between membrane and nucleus
  • Cytosol: fluid portion of cytoplasm that surrounds organelles
  • Organelles: “tiny organs”
• Nucleus: large organelle that houses most of the DNA of a cell
  • DNA: genetic material of the cell, contains hereditary units called genes
  • Nucleoli: sites of synthesis of rRNA

Cell Organelles

• Rough ER: studded with ribosomes, factory for secretory, membrane, and organellar proteins
• Smooth ER: lacks ribosomes, synthesizes fatty acids and steroids
• Golgi Complex: extends through regions of cytoplasm, protease for secretory, membrane, and organellar proteins
• Ribosomes: sites of protein synthesis
• Mitochondria: powerhouse of the cell, generates most of the ATP through aerobic respiration
• Lysosomes: break down a wide variety of molecules that come into the cell by endocytosis
• Cytoskeleton: network of protein filaments that extends through cytosol, provides structural framework for the cell
• Proteasomes: continuously cause destruction of unneeded, damaged, or faulty proteins

Cell Cycle

• Orderly sequence of events by which a somatic cell duplicates its contents and divides into two
• Cell cycle consists of two major periods: Interphase and Mitotic phase
• Interphase has three sections: G1, S, and G2
• Mitosis has four stages: Prophase, Metaphase, Anaphase, and Telophase

Elements in Biomolecules

• Oxygen is a constituent of water (H2O) and many organic molecules.
• Oxygen is used to generate ATP (adenosine triphosphate), the energy currency of cells.

Carbon in Biomolecules

• Carbon forms the backbone of chains and rings in all organic molecules, including carbohydrates, lipids, proteins, and nucleic acids.

Hydrogen in Biomolecules

• Hydrogen is a constituent of water (H2O) and most organic molecules.
• The ionized form of hydrogen (H+) contributes to the acidity of body fluids.

Nitrogen in Biomolecules

• Nitrogen is a component of all proteins and nucleic acids.

Nervous Tissue

• Detects changes in the body's internal or external environment and elicits an appropriate response

Structure of Nervous Tissue

• Made up of two types of cells: neurons and neuroglia
• Neuroglia do not conduct action potential or carry impulses, but serve supportive roles

Structure of Neurons

• Consist of three parts:
  • Cell body: contains nucleus and organelles
  • Dendrite: input portion of the cell, short, branched processes
  • Axon: output portion of the cell, single, thin, process that can be very long

Function of Neurons

• Convert stimuli to electrical signals, known as action potential or nerve impulse
• Stimulus creates a change that activates an impulse, received by the dendrite, and an output signal sent by the axon to another neuron, muscle fiber, or gland to respond or continue to carry the signal

Types of Neuroglia

• Four types:
  • Astrocytes
  • Microglial cells
  • Ependymal cells
  • Oligodendrocytes

Ribosomes

• Sites of protein synthesis where proteins are built
• Characterized by high content of ribosomal RNA, hence the name
• Composed of large and small subunits
• Can be found attached to Rough Endoplasmic Reticulum (Rough ER) or freely floating in cytoplasm as "free ribosomes"

Endoplasmic Reticulum (ER)

• A network of membranous structures in the form of flattened sacs and tubules
• Rough ER: studded with ribosomes, responsible for synthesizing secretory, membrane, and organellar proteins
• Smooth ER: lacks ribosomes, involved in synthesizing fatty acids and steroids, and detoxifying substances in liver cells

Golgi Complex

• Receives proteins after they are processed in Rough ER
• Consists of 3-20 cisternae, resembling a stack of pita bread
• Cells that secrete proteins have more extensive Golgi complexes

Smooth ER Function and Detoxification

• Smooth ER plays a role in detoxifying certain drugs, such as the sedative phenobarbital.
• Repeated administration of phenobarbital leads to changes in the smooth ER in liver cells, increasing tolerance to the drug.

Increased Tolerance and Smooth ER Changes

• Prolonged administration of phenobarbital results in increased tolerance, requiring higher dosages to achieve the same degree of sedation.
• Repeated exposure to the drug triggers an increase in the amount of smooth ER and its enzymes to protect the cell from toxic effects.

Cellular Adaptation and Treatment

• As the amount of smooth ER increases, higher dosages of the drug are needed to achieve the original effect, demonstrating how changes in a cell's organellar makeup affect treatment efficacy.

Lining Tissue

• Bladder lining is composed of transitional epithelium
• Blood vessels are lined with simple squamous epithelium
• Parotid gland is lined with stratified cuboidal epithelium
• Vaginal canal lining is made up of stratified squamous epithelium
• Simple columnar epithelium lines the small intestine
• The right main bronchus is lined with simple columnar epithelium
• The male urethra is lined with transitional epithelium

Musculoskeletal Symptoms

• Characteristics of Marfan syndrome include disproportionately long and slender limbs
• Abnormal curvature of the spine, known as scoliosis, is a common symptom
• Joint flexibility is often abnormal in individuals with Marfan syndrome

Ocular Symptoms

• A common eye problem in Marfan syndrome is dislocation of the lens

Cardiovascular Symptoms

• Valvular disorders are a common heart problem associated with Marfan syndrome
• Aortic dissection or aneurysm is a serious cardiovascular complication of Marfan syndrome

Cell Cycle and Mitosis

• During mitosis, the replicated DNA is divided equally between two daughter cells
• Mitotic phase consists of:
  • Prophase: chromatin condenses, nuclear membranes break down, and spindles form at opposite poles
  • Metaphase: chromosomes align at the metaphase plate
  • Anaphase: paired chromosomes separate and move to opposite poles
  • Telophase: chromosomes form into distinct new nuclei in emerging daughter cells

Tissue Types

• Epithelial tissue:
  • Covers body surfaces, lines hollow organs and ducts, and forms glands
  • Functions: physical barrier, secretion, absorption
  • Classes of epithelial tissue:
    • Simple squamous
    • Simple cuboidal
    • Simple columnar
    • Pseudostratified columnar
    • Stratified squamous
    • Stratified cuboidal
    • Stratified columnar

Signaling Molecules

• Local mediators:
  • Act on nearby target cells without entering the bloodstream
  • Released from cells into interstitial fluids and diffuse to act locally
  • Examples: cytokines, nitric oxide, eicosanoids, growth factors
• Hormones:
  • Steroids, thyroid hormone, nitric oxide
  • Travel through bloodstream to reach target cells
• Extracellular messengers:
  • Receptor binding: specificity, affinity, saturation, competition

Cell Injury and Adaptation

• Causes of cell injury:
  • Genetic defects
  • Ischemia
  • Infections
  • Toxic substances
  • Nutritional deficiencies
• Cell adaptation:
  • Hypertrophy: increase in cell size, resulting in organ enlargement
  • Hyperplasia: increase in cell number
  • Atrophy: decrease in cell size and function
  • Metaplasia: replacement of one cell type with another
• Types of cell death:
  • Apoptosis
  • Autophagy
  • Necrosis

Inflammation

• Causes of inflammation:
  • Infections
  • Tissue necrosis
  • Foreign bodies
  • Immune reactions
• The 5 Rs of inflammation:
  • Recognition of the injurious agent
  • [Rest omitted]
• Characteristics of mediators of inflammation:
  • Vasoactive amines: histamine and serotonin
  • Leukotrienes
  • Prostaglandins
  • Cytokines
• Effects of exposure to industrial metals, especially lead
• Effects of agricultural pesticides

Connective Tissue

• Supports and protects body organs
• Stores energy in the form of fat
• Helps provide immunity against disease-causing agents
• Functions:
  • Binds together, supports, and strengthens other tissues
  • Protects and insulates internal organs
  • Serves as a major transport system within the body (blood is a form of CT)
  • Primary location of stored energy reserves (adipose tissue)
  • Main source of immune function
• Components:
  • Extracellular matrix: materials between cells (protein fibers, ground substance)
• Types:
  • Areolar CT
  • Adipose tissue
  • Dense regular CT (muscle)
  • Dense irregular (epidermis)
  • Cartilage
  • Bone
  • Blood
• Cells:
  • Fibroblasts (in muscle)
  • Macrophages (develop from monocytes, carry out phagocytosis)
  • Plasma cells (develop from B lymphocyte, secrete antibodies)
  • Mast cells (abundant alongside blood vessels that supply CT, produce histamine)
  • Adipocytes (CT cells that store TG)

Muscle Tissue

• Contracts to produce movement
• Maintains posture
• Generates heat
• Types:
  • Skeletal:
    • Striated, tubular, and multi-nucleated
    • Voluntary
    • Usually attached to a skeleton
  • Smooth:
    • Non-striated, spindle-shaped, uninucleate
    • Involuntary
    • Covers walls of internal organs
  • Cardiac:
    • Striated, branched, and uninucleate
    • Involuntary
    • Covers walls of the heart

Nervous Tissue

• Detects and responds to changes in external or internal environment
• Two types of cells:
  • Neurons:
    • Sensitive to a variety of stimuli
    • Convert stimuli to electrical signals (action potentials) or "nerve impulses"
    • Action potentials are then conducted to another neuron, muscle, or fiber or gland
    • 3 basic parts: cell body, dendrite, axon
  • Neuroglia:
    • Do not conduct action potentials
    • Supportive functions
    • 4 types: astrocytes, microglial cells, ependymal cells, oligodendrocytes

Cell Signaling

• The communication that exists between cells of the body to coordinate activities
• Plasma membrane is:
  • Highly permeable to non-polar molecules (oxygen and steroids)
  • Moderately permeable to small, uncharged molecules (water)
  • Impermeable to ions and large, uncharged polar molecules (glucose)
• Cell-to-cell communication utilizes 3 methods:
  • Gap junctions
  • Cell-to-cell binding
  • Extracellular chemical messengers

Extracellular Messengers

• Hormones (endocrine signaling)
• Neurotransmitters (neurotransmission)
• Local mediators (paracrines and autocrines)
• Types of ECM:
  • Water-soluble (majority)
  • Lipid-soluble

Plasma Membrane Receptors

• Ion channel receptor
• Enzyme receptor
• Enzyme-coupled receptor
• G-protein coupled receptor (largest family)

Electrochemical Gradient

• Concentration gradient: difference in concentration of a substance between inside and outside of cell
• Electrical gradient: difference in electrical charges between two regions
• Electrochemical gradient: combined influence of two gradients and is the net driving force acting on an ion

Cell Junctions

• Tight junctions

• Adherence junctions

• Desmosomes

• Hemidesmosomes

• Gap junctions### Heat-Related Illnesses

• Heat cramps occur due to loss of electrolytes through sweating

• Heat exhaustion is the most common heat-related illness, caused by the body's inability to compensate for hypovolemia due to water depletion, leading to sudden onset of prostration and collapse

• Heat stroke occurs when thermoregulatory mechanisms fail, causing sweating to cease and core body temperature to rise to high levels (up to 106°F), resulting in:

  • Peripheral vasodilation and peripheral pooling of blood
  • Decreased effective circulating blood
  • Necrosis of muscles and myocardium, leading to arrhythmias and disseminated intravascular coagulation (DIC)
  • Typically affects individuals with cardiovascular disease or those engaging in intense physical activity

Cold-Related Injuries

Hypothermia

• Occurs when the body is exposed to low temperatures for a prolonged period
• Symptoms include loss of consciousness, bradycardia, and atrial fibrillation at core temperatures around 90°F
• Damage caused by:
  • Direct effects of crystallization of intracellular and extracellular water
  • Indirect effects of circulatory changes

Cold-Related Injuries Continues

• Trench foot: caused by vasoconstriction and increased permeability due to slowly falling temperatures, leading to edematous changes
• Frostbite: caused by ischemia resulting from sudden and persistent fall in temperature
  • Vascular injury and increased permeability occur when temperature returns to normal