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Ganong Physiology Notes (Ch1 & Ch2)

Body Fluid Compartments

An average young adult male’s body is composed of approximately 60% water, with body composition ideas summarized as about 18% protein, 7% minerals, 15% fat, and 60% water. The body’s water is partitioned into two primary compartments: intracellular fluid (ICF), which is inside the cells, and extracellular fluid (ECF), which is outside the cells. The extracellular fluid is the “internal sea” in which cells reside and exchange nutrients and wastes. It constitutes about 1/3 of total body water, roughly 20% of body weight, and is composed of plasma (approximately 5% of body weight) and interstitial fluid (approximately 15%). In contrast, the ICF makes up about 2/3 of total body water, about 40% of body weight. Cells live in this interstitial fluid, taking up nutrients and oxygen and releasing wastes into it. Fluid movement is tightly regulated to maintain homeostasis. Abnormal accumulation of interstitial fluid is defined as edema.

Units for Measuring

Physiological processes are more meaningfully described in terms of moles, equivalents, and osmoles rather than mass per volume because they reflect the number of molecules, charges, or particles. The key relationships are:

  • 1 mole = gram-molecular weight (MW) of a substance, i.e., its molecular weight in grams. One mole contains Avogadro’s number of particles, N_A = 6.02 imes 10^{23}. Thus, 1 mol NaCl = 58.5 g, so 1 mmol NaCl = 58.5 mg.

  • 1 mmol = 10^{-3} mol; 1 μmol = 10^{-6} mol.

  • 1 Eq (equivalent) is the amount of substance that supplies or consumes 1 mole of charge, adjusted for valence: 1 ext{ Eq}= rac{1 ext{ mol}}{z} where z is the valence. Example: Na⁺ (z=1) has 1 ext{ Eq}=23 ext{ g}; Ca²⁺ (z=2, M ≈ 40 g/mol) gives 1 ext{ Eq}= rac{40}{2}=20 ext{ g}. A milliequivalent is 1 ext{ mEq}= rac{1}{1000} ext{ Eq}. Electrical equivalence is not the same as chemical equivalence.

  • Normality (N) equals the number of gram equivalents per liter of solution. For example, 1 N HCl contains 1 equivalent of H⁺ and 1 equivalent of Cl⁻ per liter, equating to 36.5 g/L (H⁺ 1.0 g and Cl⁻ 35.5 g).

Water, Electrolytes, and Acid/Base

Water is a polar solvent with a dipole moment because oxygen is more electronegative than hydrogen, enabling dissolution of many charged species and forming hydrogen bonds between water molecules. Water’s physiologic properties include high surface tension, high heat of vaporization and heat capacity, and a large dielectric constant, all of which support heat transfer and electrical conduction in the body. Electrolytes are compounds that dissociate into cations and anions in water (e.g., Na⁺, K⁺, Ca²⁺, Mg²⁺, Cl⁻, HCO₃⁻). These ions are unevenly distributed across fluid compartments and are essential for maintaining membrane potentials and action potential generation. In physiology, electrolytes are concentrated differently inside and outside cells and are actively managed by pumps (e.g., Na⁺/K⁺ ATPase) to sustain electrical gradients and cellular function.

pH and Buffering

pH is defined as ext{pH}=-\log_{10}[H^+], i.e., the negative logarithm of hydrogen ion concentration. Pure water at 25 °C has pH 7.0, with [H^+]=10^{-7} ext{ mol/L}. Each unit change in pH corresponds to a tenfold change in [H^+]. Physiological pH values are tightly regulated: normal plasma is about 7.35–7.45, gastric fluid around 3.0 (acidic), and pancreatic secretions around 8.0 (alkaline). pH influences enzyme activity and protein structure.

Buffer systems resist pH changes by binding or releasing H⁺. The isohydric principle states that all buffers in a solution share the same [H⁺]; measuring one buffer provides information about others. The Henderson–Hasselbalch equation relates pH, pKa, and the ratio of conjugate base to acid:
ext{pH}= ext{p}Ka+\log{10} rac{[ ext{A}^-]}{[ ext{HA}]}

Best buffering occurs when pH ≈ pKa, i.e., when
rac{[ ext{A}^-]}{[ ext{HA}]} ext{ is near } 1. The carbonic acid–bicarbonate buffer system is central to extracellular buffering and is linked to lung CO₂ removal. Other important buffers include phosphate systems and protein buffers.

Diffusion and Osmosis; Tonicity and Osmolarity

Diffusion is the movement of particles from regions of high concentration to low concentration due to random thermal motion, resulting in net flux down a concentration gradient. The time to reach diffusion equilibrium over a distance L scales with L^2. Fick’s law summarizes diffusion rate: larger surface area, steeper concentration gradient, and thinner barriers all increase diffusion rate.

Osmosis is the diffusion of water across a membrane that is permeable to water but impermeable to solutes, moving from the region of lower solute concentration to higher solute concentration. Osmotic pressure is the pressure required to stop water movement into the more concentrated solution. Osmolarity is osmoles per liter of solution; osmolality is osmoles per kilogram of solvent. For dilute aqueous solutions, osmolality ≈ osmolarity because the density of water is close to 1 kg/L.

Osmolality and tonicity describe the effective osmolality relative to plasma. Isotonic solutions have the same osmolality as plasma; hypertonic solutions have higher osmolality; hypotonic solutions have lower osmolality. For example, 0.9% saline is isotonic with plasma; 5% glucose is initially isotonic but becomes hypotonic as glucose is metabolized.

Donnan effect describes how nondiffusible charged particles (e.g., intracellular proteins) alter the distribution of permeant ions across a membrane, changing local ion concentrations and osmolality. This effect contributes to cell volume regulation and influences membrane potential, particularly at capillary walls where uneven protein distribution exists between plasma and interstitial fluid. The Gibbs–Donnan equilibrium describes how ionic distributions balance chemical and electrical forces under these constraints.

Forces Acting on Ions; Equilibrium Potentials

Ion movement across membranes is governed by both chemical (concentration) and electrical gradients. Equilibrium potentials (Eion) occur when these forces balance, and are calculated by the Nernst equation: E{ ext{ion}}= rac{RT}{zF}\, ext{ln}\left( rac{[ ext{ion}]{ ext{outside}}}{[ ext{ion}]{ ext{inside}}}
ight)
where R is the gas constant, T is temperature in Kelvin, z is ionic valence, and F is Faraday’s constant. At 37 °C this can be approximated as
E{ ext{ion}}\approx rac{61.5 ext{ mV}}{z}\log{10} rac{[ ext{outside}]}{[ ext{inside}]}

Examples from physiology:

  • Cl⁻: E{Cl} ≈ −70 mV; higher Cl⁻ outside tends to drive Cl⁻ inward chemically, but the negative interior drives Cl⁻ outward, balancing at E{Cl} ≈ −70 mV.

  • K⁺: E_K ≈ −90 mV; despite a strong outward chemical gradient, the negative interior pulls K⁺ inward; the resting potential sits around −70 mV, indicating more K⁺ remains outside than diffusion alone would predict.

  • Na⁺: E_Na ≈ +60 mV; with higher outside Na⁺, Na⁺ would tend to influx, but the resting potential remains negative due to other ions and active transport.

The Na⁺/K⁺ ATPase pump maintains low intracellular Na⁺ and high intracellular K⁺, pumping 3 Na⁺ out and 2 K⁺ in per ATP cycle, thereby contributing directly to the membrane potential (electrogenic effect). Its activity is essential to counteract passive diffusion tendencies and to maintain the ionic gradients required for signaling.

Establishment of the Membrane Potential

The membrane potential arises from the combination of ion concentration gradients and the selective permeability of the membrane. The K⁺ gradient drives K⁺ out of the cell, while the electrical gradient pulls K⁺ back in. At equilibrium, net K⁺ movement is balanced, yielding a resting membrane potential around −70 mV. The Na⁺/K⁺ ATPase further maintains the gradients by actively exporting Na⁺ and importing K⁺, ensuring that the resting potential remains negative and that intracellular Na⁺ is low and K⁺ is high. Although only a small fraction of total ions participate directly in the membrane potential, these gradients are central to excitability and signaling.

Energy Production: ATP; Oxidative Phosphorylation; and Cellular Energy Use

ATP is the primary energy currency of the cell. Its hydrolysis releases energy that drives muscle contraction, active transport, and biosynthetic reactions. The body also uses ATP in sequential hydrolysis (ADP → AMP) to release additional energy in certain pathways. The main ATP production process is oxidative phosphorylation, which uses a proton gradient across the mitochondrial inner membrane to drive the synthesis of ATP. About 90% of basal oxygen consumption occurs in mitochondria, and roughly 80% of that oxygen consumption is coupled to ATP synthesis.

Cellular energy use distribution (illustrative):

  • Approximately 27% for protein synthesis.

  • About 24% for Na⁺/K⁺ ATPase activity (maintenance of membrane potential).

  • ~9% for gluconeogenesis.

  • ~6% for Ca²⁺ ATPase (maintaining low cytosolic Ca²⁺).

  • ~5% for myosin ATPase during muscle activity.

  • ~3% for ureagenesis.

Molecular Building Blocks: Nucleotides, Nucleic Acids, and Nucleic Building Blocks

Nucleosides consist of a sugar (ribose in RNA; 2′-deoxyribose in DNA) bound to a nitrogenous base (purine or pyrimidine). Nucleotides add one or more phosphate groups to a nucleoside and form the backbone of RNA and DNA, as well as coenzymes such as NAD⁺, NADP⁺, and ATP. Bases are purines (adenine A, guanine G) or pyrimidines (cytosine C, thymine T in DNA, uracil U in RNA). Dietary nucleic acids are digested to bases; synthesis mainly occurs in the liver.

DNA features: found in bacteria, nuclei, and mitochondria. Structure consists of two long nucleotide chains with A–T and G–C hydrogen bonds forming a double helix; histones compact DNA into chromosomes. The human genome in diploid somatic cells comprises 46 chromosomes. DNA replication during mitosis (somatic cell division) yields identical daughter cells: the double helix unwinds; DNA polymerase synthesizes complementary strands; each daughter cell receives one complete genome.

RNA features: single-stranded; contains uracil (U) instead of thymine; ribose sugar. Transcription copies DNA to RNA via RNA polymerase. Types include mRNA (coding sequences for proteins), tRNA (adaptor for amino acids during translation), and rRNA (ribosomal components). Translation on ribosomes converts mRNA into polypeptides, with tRNA delivering amino acids to the growing chain; ribosomes can be free in cytosol or bound to the rough endoplasmic reticulum (RER).

Amino Acids and Proteins

Amino acids are the building blocks of proteins. They are classified as acidic, neutral, or basic according to the balance of carboxyl (-COOH) and amino (-NH₂) groups. Essential amino acids must be obtained from the diet; conditionally essential amino acids (e.g., arginine, histidine) are required during growth or recovery; nonessential amino acids can be synthesized in the body. Peptides are short chains of 2–100 amino acids; proteins are longer than 100 amino acids. An amino-acid table lists aliphatic, hydroxyl-substituted, sulfur-containing, aromatic, acidic, and basic amino acids and their abbreviations.

Catabolism of amino acids is classified as ketogenic (yielding acetyl-CoA or acetoacetate) or glucogenic (yielding intermediates that feed into gluconeogenesis). Transamination and entry into the citric acid cycle are illustrated by amino acids feeding into acetyl-CoA, oxaloacetate, and other intermediates to support energy production or glucose synthesis (gluconeogenesis).

Carbohydrates

Carbohydrates are organic molecules with equal amounts of carbon and water. Monosaccharides include pentoses (e.g., ribose) and hexoses (e.g., glucose). Disaccharides and polysaccharides (e.g., sucrose, glycogen) are formed by linking monosaccharides. Dietary and circulating sugars are mainly hexoses; glucose is the principal circulating sugar. Glycoproteins on membranes help in targeting and recognition. Normal fasting plasma glucose is about 70-110 ext{ mg/dL}, with arterial glucose typically higher than venous by ~15–30 mg/dL.

Glucose metabolism begins with phosphorylation to glucose-6-phosphate by hexokinase (general, low Km, not insulin-dependent) or glucokinase (liver; insulin-dependent). Fates of glucose-6-phosphate include glycogenesis (glycogen synthesis), glycogenolysis (glycogen breakdown), and glycolysis (toward pyruvate or lactate). Gluconeogenesis converts lactate or non-glucose substrates into glucose. Glucose can also be a precursor for fatty acids; fats can contribute to glucose formation only modestly (glycerol can feed the pathway, but acetyl-CoA cannot be converted back to pyruvate in significant quantities).

Lipids and Lipid Transport

Lipids include fatty acids and derivatives, neutral fats (triglycerides), phospholipids, and sterols. Fatty acids have even-numbered carbon chains; saturated fatty acids have no double bonds, whereas unsaturated fatty acids have one or more double bonds. Phospholipids form the structural basis of cellular membranes and also serve as lipid signaling precursors. Fatty acids are a major energy source. Neutral fats are stored in adipose tissue; their breakdown releases free fatty acids (FFAs) into the circulation for energy.

Brown fat is a special adipose tissue type rich in mitochondria and sympathetic innervation, more abundant in infants but present in adults in smaller quantities. It contributes to thermogenesis.

Plasma lipids and transport involve lipoprotein particles that solubilize otherwise water-insoluble lipids. Lipoproteins have a hydrophobic core (triglycerides and cholesteryl esters) and a hydrophilic outer corona of phospholipids and proteins. Major lipoprotein families include chylomicrons (originating in the intestinal mucosa; transport dietary triglycerides), VLDL, IDL, LDL, and HDL (endogenous transport and reverse cholesterol transport). The exogenous pathway moves dietary TG from intestine to tissues and liver; the endogenous pathway handles TG synthesis and transport from liver to tissues. Lipoprotein lipase (LPL) and LDL receptors regulate lipid delivery and clearance.

Nucleotides, Nucleic Acids, and Genetic Material (Expanded)

Nucleosides are composed of a sugar (ribose or 2′-deoxyribose) and a nitrogenous base. Nucleotides add one or more phosphate groups; nucleotides form DNA and RNA, coenzymes, and regulatory molecules. DNA comprises two antiparallel nucleotide chains with A–T and G–C hydrogen bonds forming a double helix; the human genome contains 46 chromosomes in diploid somatic cells. DNA replication conserves the genome; transcription produces RNA, which is translated into proteins. RNA types include mRNA, tRNA, and rRNA, among others. This genetic framework underpins protein synthesis, enzyme function, and cellular metabolism.

The Cell: Organelles, Structure, and Function (Chapter 2)

Cells are the basic units of life, carrying out metabolism, energy use, synthesis, communication, reproduction, and inheritance. The cytoplasm contains organelles suspended within a cytosol; the plasma (cell) membrane encloses the cell and organelles. Organelles include the nucleus, endoplasmic reticulum (ER, rough and smooth), Golgi apparatus, mitochondria, lysosomes, peroxisomes, cytoskeleton (microtubules, intermediate filaments, microfilaments), ribosomes, vacuoles, and more. The nucleus houses chromosomes, nucleolus (ribosome synthesis), and is enveloped by a nuclear membrane with nuclear pores. The endoplasmic reticulum serves as a biosynthetic network: rough ER with ribosomes synthesizes proteins; smooth ER handles lipid synthesis and detoxification; the sarcoplasmic reticulum in muscle stores Ca²⁺. Ribosomes are the sites of protein synthesis; bound ribosomes synthesize proteins destined for membranes, lysosomes, or secretion, while free ribosomes synthesize cytosolic proteins.

Golgi apparatus, organized in cis (near the ER) and trans (near the plasma membrane) regions, processes and sorts proteins and lipids, adding glycosylations and packaging for delivery inside or outside the cell. Vesicular traffic, mediated by SNARE proteins (v-SNAREs and t-SNAREs) and small GTPases, directs vesicles between ER, Golgi, lysosomes, and plasma membrane. The lysosome contains acid hydrolases and degrades internal and endocytic materials; peroxisomes host oxidases and catalases for lipid breakdown and reactive species detoxification. The mitochondrion is the powerhouse of the cell: it has its own circular genome, double membrane, cristae where oxidative phosphorylation occurs, matrix, and is maternally inherited. It is the site of ATP production, but the majority of mitochondrial proteins are encoded by nuclear DNA.

The cytoskeleton provides structural support and mediates traffic and movement within the cell. It comprises microtubules (tubulin), intermediate filaments, and microfilaments (actin). Microtubules form the mitotic spindle during cell division; microfilaments participate in cell crawling and attachment to the extracellular matrix; intermediate filaments confer mechanical resilience and serve as cell-type markers (e.g., vimentin in fibroblasts, cytokeratin in epithelial cells). Centrosomes act as microtubule-organizing centers and contain γ-tubulin to nucleate microtubules. Cilia are microtubule-based structures that move mucus and other substances on epithelial surfaces and act as sensory organelles in most cells. Cell adhesion molecules (CAMs) including integrins, cadherins, selectins, and the Ig superfamily mediate adhesion to the extracellular matrix and neighboring cells, transduce signals, regulate movement, and influence tissue architecture.

Intercellular Junctions and Communication

Intercellular junctions provide mechanical strength and selective permeability. Tight junctions (zonula occludens) seal paracellular spaces and prevent lateral diffusion of membrane proteins, maintaining cell polarity. Zonula adherens and focal adhesions anchor cells to one another and to the basal lamina, with cadherins and actin linking complexes. Desmosomes connect intermediate filaments between adjacent cells, while hemidesmosomes anchor cells to the basal lamina via integrins. Gap junctions (connexons) form cytoplasmic tunnels allowing direct passage of ions and small molecules (< ~1000 Da), enabling rapid electrical and chemical communication between adjacent cells.

Intercellular communication modes include:

  • Juxtacrine: direct membrane contact.

  • Paracrine: local diffusion through extracellular fluid to nearby cells.

  • Autocrine: signals binding to receptors on the same cell that secreted them.

  • Endocrine: hormones travel via blood/lymph to distant targets.

Receptors for chemical messengers include:

  • Ion-channel receptors (ligand-gated ion channels).

  • G-protein-coupled receptors (GPCRs).

  • Enzyme-linked receptors (tyrosine kinase receptors, etc.).

  • Intracellular receptors for lipid-soluble ligands that regulate gene transcription.

Downregulation and upregulation modulate receptor number and sensitivity. Angiotensin II is noted as an exception, increasing its receptor numbers in the adrenal cortex.

Signal Transduction: Second Messengers and Pathways

Chemical messengers bind to receptors and trigger intracellular signaling cascades with four main outcomes:

  • Ion-channel activation (altered membrane conductance).

  • G-protein activation leading to downstream signaling cascades.

  • Enzyme activation within the cell.

  • Direct transcription activation by lipid-soluble hormones binding intracellular receptors.

Two major classes of transmembrane signaling mechanisms are:

  • Ligand-gated ion channels (e.g., acetylcholine receptors).

  • G-protein-coupled receptors (GPCRs) with seven transmembrane helices; they activate G proteins (Gs or Gi) leading to the production of second messengers like cyclic AMP (cAMP) or inositol triphosphate (IP₃) and diacylglycerol (DAG).

  • Enzyme-linked receptors (such as receptor tyrosine kinases) and intracellular receptors regulate gene expression or cytosolic signaling.

Second messengers include:

  • cAMP: activates protein kinase A (PKA); PKA phosphorylates target proteins and can activate CREB in the nucleus to alter gene transcription.

  • IP₃ and DAG: IP₃ triggers Ca²⁺ release from the endoplasmic reticulum; DAG activates protein kinase C (PKC).

  • Ca²⁺ acts as a versatile second messenger, stored in the ER and released via IP₃ or ryanodine receptors; Ca²⁺ influences numerous processes including muscle contraction, secretion, and enzyme activity.

  • cGMP: regulated by natriuretic peptides and NO; activates PKG and various ion channels; important in vision and smooth muscle relaxation.

First messengers (extracellular ligands) initiate the signaling, while second messengers amplify and distribute the signal within the cell. The physiological effects of these pathways are diverse: proliferation, contraction, secretion, metabolism, and gene expression changes.

Vessicular Traffic and Secretion

Protein processing and trafficking follow a distinct path: ER → Golgi → lysosomes or plasma membrane (secretory pathway). Vesicles bud from the ER’s cis face, traverse cisternae, and fuse with the Golgi's cis face; proteins are modified (glycosylation) and sorted, then packaged into vesicles that move to the trans face for delivery to lysosomes, the plasma membrane, or extracellular space. Exocytosis involves docking of vesicles at the plasma membrane via v-SNARE/t-SNARE interactions; fusion releases cargo in a Ca²⁺-dependent manner. Endocytosis internalizes material from the plasma membrane into endosomes; pathways include phagocytosis (cell eating) and pinocytosis (cell drinking).

Apoptosis vs Necrosis; Cell Death

Apoptosis is programmed cell death under genetic control, characterized by cell shrinkage, chromatin condensation, DNA fragmentation, membrane blebbing, and eventual phagocytic removal of apoptotic bodies with minimal inflammation. Necrosis is cell death due to injury that often triggers inflammation due to membrane rupture and cellular content release. The apoptotic pathway involves caspase activation, with several caspases identified in humans as executors of the process.

Summary of Key Points from Chapter 1

  • Body fluid compartments and their relative volumes: ECF (~1/3 of TBW; ~20% of body weight), plasma (~5%), interstitial fluid (~15%), ICF (~2/3 of TBW; ~40%). Edema results from interstitial fluid accumulation.

  • Units for measuring physiology emphasize molecules and charges: moles, equivalents, osmoles; practical examples for NaCl and Ca²⁺ are provided; normality and equivalents relate to electrolyte calculations.

  • Water’s properties support solvation and conduction; electrolytes are essential for cell function and membrane potential.

  • pH and buffering systems maintain acid–base balance; Henderson–Hasselbalch equation links pH to buffer species; carbonic acid–bicarbonate is a central physiologic buffer system.

  • Diffusion, osmosis, and tonicity determine movement of solutes and water; Donnan effect introduces complexity due to impermeant intracellular proteins.

  • Ion gradients set membrane potential; the Nernst equation provides a quantitative framework; Na⁺/K⁺ ATPase maintains gradients and contributes to the resting potential.

  • Energy production centers on ATP; oxidative phosphorylation in mitochondria is the dominant ATP source; most cellular energy use is allocated to synthesis, ion transport, and muscle activity.

  • Carbohydrates, lipids, and proteins form the major biomolecules; glucose metabolism integrates glycolysis, glycogenesis, glycogenolysis, and gluconeogenesis; fatty acids provide energy through beta-oxidation and are transported by lipoproteins; lipids have storage and signaling roles.

  • Nucleotides and nucleic acids underpin genetic information and protein synthesis; DNA structure and replication ensure genome fidelity; RNA types mediate transcription and translation.

  • Cellular organelles coordinate biosynthesis, energy production, degradation, and transport; the cytoskeleton organizes internal structure and vesicle movement; mitochondria supply ATP and contain a small genome; lysosomes, peroxisomes, ER, and Golgi perform synthesis, degradation, and trafficking.

Chapter 2: Overview of Cellular Physiology

Cell Structure and Organelles

Cells contain specialized organelles performing dedicated functions: the nucleus houses DNA; the nucleolus synthesizes ribosomal RNA; the endoplasmic reticulum (ER) exists in two forms—rough (RER) with ribosomes for protein synthesis and processing, and smooth (SER) for lipid synthesis and detoxification. The Golgi apparatus processes and weights glycosylation of proteins and lipids and sorts them for delivery. Mitochondria generate most cellular ATP via oxidative phosphorylation and have their own circular genome; they are maternally inherited and show high mutation rates.

Lysosomes carry hydrolytic enzymes that digest endocytosed material and worn-out organelles. Peroxisomes contain oxidases and catalases that participate in fatty acid breakdown and reactive oxygen species detoxification. The cytoskeleton, composed of microtubules, intermediate filaments, and microfilaments, provides shape, supports intracellular transport, and integrates with motor proteins to move organelles and vesicles. Centrosomes act as microtubule organizing centers (MTOCs) and are essential for spindle formation during mitosis.

Cilia are microtubule-based organelles that move mucus over epithelia and act as sensory organelles in many cells. The nucleus, chromatin, nuclear envelope, nucleoplasm, and nucleolus define nuclear architecture required for transcription and genome maintenance. The nuclear pore complex regulates traffic between the nucleus and cytoplasm.

Membrane Structure and Transport

The cell membrane is a phospholipid bilayer with amphipathic properties: hydrophilic heads face aqueous environments; hydrophobic tails face inward. It contains cholesterol and various glycolipids that contribute to membrane stability and signaling. Membrane proteins are either integral (embedded, possibly spanning the membrane) or peripheral (associated with the membrane surface). The membrane is selectively permeable, allowing passive diffusion of small nonpolar molecules and water via aquaporins, while larger or charged species require transport proteins, channels, or vesicular mechanisms.

Membrane transport mechanisms include:

  • Passive transport: diffusion and facilitated diffusion through carrier proteins, moving down concentration/electrical gradients without energy input.

  • Active transport: energy-dependent transport against gradients, typically via pumps such as Na⁺/K⁺-ATPase, Ca²⁺-ATPase, or H⁺-ATPases.

  • Secondary active transport: uses energy stored in the gradients established by primary active transport (e.g., Na⁺-glucose cotransport).

  • Endocytosis and exocytosis: vesicular transport processes that move materials into or out of the cell; vesicles fuse with or bud from the plasma membrane; docking often involves SNARE proteins.

Cytoskeleton and Cellular Polarity

The cytoskeleton supports cell shape and movement and provides tracks for vesicular transport. Microtubules (tubulin) are vital for mitosis and organelle transport; intermediate filaments provide mechanical resilience and serve as cell-type markers; microfilaments (actin) participate in cell motility and membrane protrusions. Centrioles organize microtubules during cell division. cilia and basal bodies drive movement of mucus and sensory signaling. Adhesion molecules (CAMs) like integrins, cadherins, selectins, and the Ig superfamily anchor cells to the extracellular matrix and other cells, mediate signal transduction, and influence tissue architecture and inflammatory responses.

Intercellular Communication and Receptors

Cells communicate via gap junctions (direct cytoplasmic exchange of ions and small molecules) and through chemical messengers that act on receptors on nearby or distant cells. Juxtacrine signaling requires direct membrane contact; paracrine and autocrine signaling involve diffusion in the extracellular fluid with local effects; endocrine signaling uses the bloodstream for distant targets. Receptors can be:

  • Ion channel receptors (ligand-gated channels) that rapidly alter membrane conductance.

  • G-protein-coupled receptors (GPCRs), which activate intracellular G proteins to produce second messengers (e.g., cAMP, IP₃, DAG).

  • Enzyme-linked receptors with catalytic activity, often tyrosine kinases, that initiate intracellular signaling cascades.

  • Intracellular receptors for lipophilic ligands that regulate gene transcription.

Second messengers translate extracellular signals into intracellular actions. Key second messengers include cAMP, IP₃, DAG, Ca²⁺, and cGMP, which regulate enzyme activity, ion channels, and gene expression. The signaling landscape allows diverse physiological outcomes: smooth muscle contraction, neuronal signaling, secretion, and proliferation.

Apoptosis and Cellular Injury

Apoptosis is a controlled, genetically programmed form of cell death that preserves surrounding tissue integrity by avoiding inflammation. Necrosis is uncontrolled cell death typically due to injury, provoking inflammation. The apoptotic process involves caspase activation, DNA fragmentation, chromatin condensation, membrane blebbing, and phagocytic clearance of apoptotic bodies. Disruptions in these processes can contribute to disease, including cancer and degenerative conditions.

Interconnections Across Chapter 1 and Chapter 2

  • The biochemical building blocks (nucleotides, amino acids, carbohydrates, and lipids) underpin energy metabolism, protein synthesis, and membrane composition, all of which determine cellular structure, signaling, and function.

  • Ionic gradients and membrane potential are prerequisites for excitability in muscle and nerve and drive the transport of many solutes, including neurotransmitters and ions.

  • Vesicular trafficking and the secretory pathway coordinate the delivery of proteins and lipids essential for membrane integrity, signaling, and extracellular signaling.

  • Second-messenger pathways (cAMP, IP₃/DAG, Ca²⁺, and cGMP) provide rapid, versatile control of cellular activities, linking receptor activation to functional responses.

Practical and Clinical Implications

  • Osmolality and tonicity are central to diagnosing dehydration, overhydration, and electrolyte disturbances; intravenous fluids must be chosen with tonicity in mind to avoid cellular swelling or shrinkage.

  • Donnan effects influence capillary exchange and can affect cell volume regulation, particularly in pathological states with altered protein content or permeability.

  • Understanding ion channels and transporters is critical for interpreting pharmacologic effects, such as diuretics targeting Na⁺ reabsorption or drugs that modulate GPCR signaling.

  • Mitochondrial function and oxidative phosphorylation are central to energy balance; defects contribute to high-energy-demand tissue pathologies.

Equations and Key Values to Remember

  • pH: ext{pH} = -\log_{10}[H^+]

  • Henderson–Hasselbalch: ext{pH} = ext{p}Ka + \log{10} rac{[ ext{A}^-]}{[ ext{HA}]}

  • Nernst equation (general): E{ ext{ion}} = rac{RT}{zF}\, ext{ln}\left( rac{[ ext{outside}]}{[ ext{inside}]} ight) Approximate at 37 °C: E{ ext{ion}} \approx rac{61.5 ext{ mV}}{z} \log_{10} rac{[ ext{outside}]}{[ ext{inside}]}

  • Resting membrane potentials (typical values): EK \approx -90 ext{ mV}, \, E{Cl} \approx -70 ext{ mV}, \, E_{Na} \approx +60 ext{ mV}

  • Na⁺/K⁺ ATPase pump stoichiometry: 3 Na⁺ out and 2 K⁺ in per ATP hydrolysis, contributing to membrane potential and ionic homeostasis.

  • ATP energy use distribution is illustrative and context-dependent, with substantial energy allocated to synthesis, pump activity, gluconeogenesis, calcium uptake, muscle contraction, and ureagenesis as described above.

Chapter 2: Final Summary

The cellular landscape combines structure, transport, signaling, and metabolism to sustain life. Organelles compartmentalize functions: the nucleus governs genetic information; the ER and Golgi coordinate protein and lipid processing; mitochondria generate chemical energy; lysosomes and peroxisomes handle degradation and detoxification. The plasma membrane, supported by a dynamic cytoskeleton, orchestrates selective permeability, receptor-mediated signaling, and intercellular communication. Intercellular junctions ensure tissue integrity, while gap junctions and a variety of signaling molecules coordinate responses across cells and organ systems. Collectively, these elements underlie the physiological processes that enable energy production, homeostasis, growth, and adaptation to internal and external environments.