Cell 1 & 2.pdf

PHYSIOLOGY: LE1 | TRANS 01 CELL 1: CELL STRUCTURE AND FUNCTION CARIE GOMEZ, MD | 08/05/2024 OUTLINE ○ Elimination of waste products th...

PHYSIOLOGY: LE1 | TRANS 01 CELL 1: CELL STRUCTURE AND FUNCTION CARIE GOMEZ, MD | 08/05/2024 OUTLINE ○ Elimination of waste products through the feces Liver: I. Cell VI. Cell Cytoskeleton II. Homeostasis A. Microfilament (Actin) ○ Metabolizes absorbed substances to more usable forms A. Regulation of Body B. Intermediate ○ Storage site of most nutrients Functions Filaments ○ Detoxifies drugs and chemicals B. Characteristic of C. Microtubule Musculoskeletal system: locomotion Control System VII. Molecular Motor Kidneys: filters plasma III. Cell composition Proteins ○ Substances needed by body: reabsorbed into the blood A. Water IV. Cell membrane ○ Substances not needed: passed through urine B. Carbohydrates A. Membrane lipids Endocrine system: regulate body functions through hormone C. Proteins B. Membrane proteins secretion D. Lipids C. Membrane Nervous system: integration of body functions E. Electrolytes carbohydrates ○ Neural: muscular and secretory function IV. Nucleus D. Fluid mosaic model ○ Sensory: detects state of the body and its environment A. Nucleolus E. Functions ○ CNS: stores information B. Nuclear membrane V. Membrane junctions ○ Motor (effector): carries out desires/actions V. Cytoplasm and its A. Tight junctions Reproductive system: generation of new beings Organelles B. Anchoring junctions Genetic control: most intricate; dictates intracellular and A. Mitochondria C. Gap junctions B. Endoplasmic extracellular functions Reticulum Immune system: recognizes self from non-self antigens C. Golgi Apparatus B. CHARACTERISTIC OF CONTROL SYSTEM D. Lysosome E. Peroxisome NEGATIVE FEEDBACK F. Filaments SUMMARY OF ABBREVIATIONS Most control systems act by negative feedback Example/s: 📖 Opposite effect → “negative” to initiating stimulus ECM/ECF extracellular matrix/fluid ○ ↑ CO2 in ECF (initiating stimulus) = ↑ ventilation = ↑ CO2 CT connective tissue excretion = ↓ CO2 in ECF TAG triglycerides ○ ↑ blood pressure (initiating stimulus) = vasodilation = ↑ ER endoplasmic reticulum blood flow = ↓ BP MW molecular weight ○ ↓ blood pressure (initiating stimulus) = vasoconstriction = ↓ ATP adenosine triphosphate blood flow = ↑ BP GA Golgi apparatus H2O2 hydrogen peroxide NICE-TO-KNOW: GAIN OF A CONTROL SYSTEM Degree of effectiveness with which a control system maintains LEGENDS constant conditions is determined by the “gain” of negative feedback ❗ Must know 👩‍⚕️ Lecturer 📖 Book 🖥 Presentation 📝 Old Trans 𝐺𝑎𝑖𝑛 = 𝐶𝑜𝑟𝑟𝑒𝑐𝑡𝑖𝑜𝑛 𝐸𝑟𝑟𝑜𝑟 LEARNING OBJECTIVES At the end of the lecture, the student should be able to: ❗If negative feedback is no longer working → positive feedback ✔ Describe the cell POSITIVE FEEDBACK (VICIOUS CYCLE) ✔ Discuss the organization of the human body Same effect ✔ Explain homeostasis Does not always lead to stability → INSTABILITY → DEATH ✔ Discuss the control system Sometimes useful ✔ Discuss the composition of the cell ○ Wound = ↑ clotting factors = clot = wound healing ✔ Identify the different structures that make up the cell If uncontrolled = ↑ clotting factors → unwanted clots CELL = atherosclerosis ○ Parturition (childbirth) = ↑ oxytocin = ↑ uterine.Basic living unit of the body The human body contains about 35-40 trillion cells Organization of the human body: 📖 ○ contractions = promote delivery of baby Ovulation = ↑ estrogen Without positive feedback: ↑ estrogen = ↓ LH, ↑ FSH ○ Cells → tissues → organs → systems → organism With positive feedback: ↑ estrogen = ↑ LH, ↑ FSH HOMEOSTASIS FEED-FORWARD CONTROL Maintenance of nearly constant conditions in the internal environment (ECM) of cells Rapid neural transmission during contraction ○ Nerve → impulses → muscles → contraction 👩‍⚕️ Used by the nervous system to control muscle contractions A. REGULATION OF BODY FUNCTIONS Division of labor between systems Respiratory system: 👩‍⚕️ ADAPTIVE CONTROL (DELAYED NEGATIVE FEEDBACK) ○ Distribution and replenishment of O2 Corrects feed-forward mechanism ○ Removes CO2 Enables the neuromuscular system to develop smooth and GIT: precise movement → paulit-ulit na movement (practice) ○ Absorbs nutrients from food LE 1 Trans 1 TG: BC, SC, LC, SC, KD, DL, CM, BM, NN, AS, RS, CT Page 1 of 7  CELL COMPOSITION NUCLEUS Protoplasm: substances that make up the cell Present in most eukaryotic cells, except: ○ Water ○ Mature RBCs ○ Carbohydrates ○ Cells within the lens of the eyes ○ Proteins Control center ○ Lipids ○ Metabolic activities ○ Electrolytes ○ Reproduction/replication DNA (large amounts) A. WATER RNA 70-85% of total cell mass Contains the genome (46 chromosomes) ○ Except fat cells (95% lipids) ○ 44 autosomes (somatic) May be free or bound ○ 2 sex chromosomes Principal medium for transport of substances and chemical A. NUCLEOLUS reactions Aggregates of RNA and proteins → ribosome synthesis B. CARBOHYDRATES No limiting membrane 1% of total cell mass (continuously utilized as energy source), Enlarged in highly synthesizing and growing cells except: B. NUCLEAR MEMBRANE ○ Liver cells: 6% total cell mass ○ Muscle cells: 3% total cell mass AKA nuclear envelope 📖 CHO in the form of dissolved glucose is always present in the Bilayer membrane ❗ ECF → readily available to the cell ○ Outer membrane: continuous with the ER ○ Immediate source of energy Penetrated by nuclear pores: Types: ○ Allow molecules with MW 44,000 to pass through ○ Monosaccharides Glucose, galactose, fructose CYTOPLASM AND ITS ORGANELLES ○ Disaccharides Cytosol: jelly-like fluid portion Maltose, sucrose, lactose ○ Polysaccharides A. MITOCHONDRIA Glycogen, cellulose, pectin lignin ○ Mucopolysaccharides “Powerhouse” of the cell CT matrix ○ Generating energy in the form of ATP Stored as glycogen C. PROTEINS 10-20% of total cell mass (most abundant next to water) 2 types: ○ Structural Fibrillar (found outside the cell) Figure 1. Mechanism of Action for Production of ATP Collagen and elastin fibers of CT Composed mainly of two lipid bilayer protein membranes Vessel walls ○ Outer membrane Tendons and ligaments ○ Inner membrane Filamentous Cristae Microtubules (provide cytoskeletons for the ff:) Infoldings where oxidative enzymes are ○ Cilia attached ○ Nerve axons Matrix ○ ○ Functional (globular) 👩‍⚕️ Mitotic spindles Cell adhesion molecules Contains large quantities of dissolved enzymes for extracting energy from nutrients Site of Ca2+ sequestration during muscular relaxation along Pumps with the sarcoplasmic reticulum Carriers Regulates apoptosis (programmed cell death) Ion channels Contains DNA → self-replicative Receptors Enzymes (catalyzes chemical reactions) Immunoglobulins (antibodies) ○ Many in highly metabolizing cell 👩‍⚕️ Genome is smaller than that of the nucleus NICE-TO-KNOW D. LIPIDS The average mitochondrion has a life span of 10 days 2% of total cell mass ○ Except fat cells (95% TAG) ❗CENTRAL CORE DISEASE. Autosomal dominant trait Fat-soluble Muscle weakness due to loss of mitochondria ○ Cholesterol Characterized by RYR (Ryanodine Receptor) defect ○ TAG ○ ↑↑ intracellular Ca2+ concentration = ↑↑ mitochondrial ○ Phospholipids Energy reserve → storehouse of energy-giving nutrients 📖. uptake and Ca2+ overload → LOSS OF MITOCHONDRIA USES OF ATP E. ELECTROLYTES Membrane transport AKA ions Synthesis of chemical compounds into the cell ○ Cations (positive) Mechanical work ○ Anions (negative) ○ Active process in the body Provide inorganic chemicals for cellular reactions LE 1 Trans 1 TG: BC, SC, LC, SC, KD, DL, CM, BM, NN, AS, RS, CT Page 2 of 7 NICE-TO-KNOW ○ Receives products from the ER ATP Mid-portion ○ Normal currency of the cell ○ Sorting/packaging/processing center Na-K pump primarily consumes ATP (Gastador) Trans-portion Muscular contraction (Gastador) ○ Located closest to the membrane ○ Secretes processed products B. ENDOPLASMIC RETICULUM ❗ ⚫ MEMORY AID - GA IS THE SHOPEE OF THE CELL ⚫ Continuation of the outer nuclear membrane Cis: Shopee receives your parcel from their partner store ⚫ Mid:. ROUGH ENDOPLASMIC RETICULUM Sorting center Trans: Delivery courier Embedded with ribosomes (granular appearance) D. LYSOSOME ○ Site of protein synthesis Develops from nuclear membrane Formed from golgi complex Modifies proteins Digestive system of the cell 📖 Glycosylation ○ Autophagy: digestion of cellular components. SMOOTH ENDOPLASMIC RETICULUM “housekeeping process” ○ Autolysis: destruction of the whole cell Part of ER with no attached ribosomes (agranular ER) Contains hydrolytic enzyme Develops from RER ○ Most acidic portion Site of lipid synthesis (phospholipids and cholesterol) → Lowest pH: 4.5 - 5 steroid hormones, sex hormones, and Vit. D Activates hydrolases Site of breakdown of carbohydrates Inactivates bacterial metabolic systems. In muscles (sarcoplasmic reticulum) ○ Ca2+ storage, release, and sequestration ENZYME SUBSTRATE TYPE In the liver (Acid Hydrolases) ○ Modifies/detoxifies substances Ribonuclease RNA Nuclease Abundant in highly secreting cells. ❗MUST KNOW In large and prominent nucleolus, it should be highly Deoxyribonuclease DNA Nuclease synthesizing in growing cell Phosphatase Phosphate Esters Greater number of mitochondria, it should be highly metabolizing cell Glycosidase Complex Glycosidase Trans-portion located closest to the membrane is responsible carbohydrates for the secretion. Arylsulfatases Sulfate Esters C. GOLGI APPARATUS Closely related to ER and has membranes similar to those of Cathepsins Proteins Proteases the agranular ER Collagenases Collagens Proteases Packaging system of the cell ○ Responsible for sorting and final processing. Table 1. List of Enzymes and substrates along with their type of Membrane-enclosed sacs hydrolases Polarized structure (irreversible) Prominent in secretory cells ❗LYSOSOMAL STORAGE DISEASE ○ substances are extruded. Types of delivery 📖 Located on the side of the cell from which the secretory Occurs when lysosomal enzymes are genetically absent → neurons are affected ○ Constitutive Engorgement of lysosomes Ex: Does not require a signal Continuous synthesis and secretion For repairs, renewal of organelle structure 👩‍⚕️ ○ ○ Fabry Disease (α-galactosidase A deficiency) Gaucher Disease (β-glucocerebrosidase deficiency) Ex. ○ Tay-sachs Disease (hexosaminidase A deficiency). Cellular waste excretion E. PEROXISOME (MICROBODIES) Mucous secretion ○ Regulated Pathway Formed from SER Needs signal Self-replicative Contains oxidative enzymes (oxidases or catalases) another cell (hormones) Ex: 👩‍⚕️ Cells needs to release a substance that will affect ○ Capable of combining oxygen with hydrogen ions derived from different intracellular chemicals to form Insulin delivery in cases of elevated blood H2O2 sugar Highly oxidizing substance ○ ↑ blood sugar → b-cells produce insulin → Used in association with catalase to oxidize many processed by GA → secreted by the substances that might otherwise poisonous to the cell NICE-TO-KNOW 📖 pancreas Newly formed proteins: Responsible for getting rid of toxic radicals 📖 Major function is to catabolize long chain fatty acids ○ Can be detected in the RER w/in 3-5 mins FILAMENTS ○ Present in the GA w/in 20 mins ○ Secreted from the cell surface w/in 1-2 hrs Provide elastic support to the cell membrane (reason why cell. Cis-portion ❗MUST KNOW can change its shape and not burst) ○ Resists pressure Act as cytoskeleton (present in all cells) ○ Closest to endoplasmic reticulum LE 1 Trans 1 TG: BC, SC, LC, SC, KD, DL, CM, BM, NN, AS, RS, CT Page 3 of 7. Proteins with fibrillar and structural functions 📝 Imagine: logistics: Transport of protein as correlated to trucking CELL CYTOSKELETON ○ Microtubule - serves as yung daanan Maintains cell structure (cell shape) ○ Mol. Motor protein - yung truck na may dala ng cargo Responsible for locomotion (cell movement) ○ ATP - gas / fuel ng sasakyan Plays an important role in intracellular transport ○ Ca2+ - susi/starter ng sasakyan 📖 A network of fibrillar proteins organized into filaments or tubules ❗KARTAGENER’S SYNDROME Immotile ciliary syndrome Autosomal recessive Characterized by: ○ Recurrent pulmonary infection (missing cilia) ○ Infertility (missing flagella in sperm) CILIA For locomotion → uniform movement Types: ○ Motile: whip-like motion (similar to sperm flagellum, except shorter) Fallopian tube Respiratory tract ○ Nonmotile (primary cilia) Occurs as a single cilium on each cell Sensory antennae MOVEMENTS IN CELL filaments, and microtubules 📖 Figure 2. Cell cytoskeleton: microfilaments, intermediate Ameboid movement ○ Seen in WBC A. MICROFILAMENT (ACTIN) Ciliary movement ○ Powered by the axoneme Maintains cell structure (present in all cells and most abundant 9 double tubules + 2 single tubules (linked by in muscle cells) protein cross-linkages) Permits cell to cell change in its shape and movement ○ Seen in fallopian tube and respiratory system ○ Functions for contractile elements in muscles Movement that occurs in the muscles ○ Involved in locomotion ○ Sliding movement due to myosin ○ Makes up the core of microvilli. ○ Serves as a linker protein (focal adhesions) - links one NON MEMBRANE BOUND STRUCTURES 👩‍⚕️ ○ cell to another cell Actin F-actin - polymerized/polymer (fibrous) Neutral fat globes Glycogen granules Ribosomes ○ G-actin - depolymerized/monomer (globular) Secretory Vesicles B. INTERMEDIATE FILAMENTS Proteasomes ○ SImilar to lysosomes Includes keratin filaments and neurofilaments ○ Site of protein degradation Made up of several proteins Nucleolus ○ Has structural function ○ Resist internal pressure CELL MEMBRANE ○ Forms flexible scaffoldings for the cell Serves as linker protein (same w/ actin) C. MICROTUBULE Made up of ⍺ and β tubulin dimers and γ tubulin (production) ○ Involved in transport of intracellular vesicles ○ Involved in the movement of chromosomes, cilia, and flagella Target of antitumor drugs ○ Vincristine and Colchicine (anti-gout medication) Prevents polymerization of tubulin dimers, thus prevents formation of microtubules ○ Taxol Stabilizes the microtubules, thus arrest cells in 📖 mitosis MOLECULAR MOTOR PROTEINS Figure 3. Cell membrane composition. AKA plasma membrane Move proteins, organelles, and other cell parts (cargo) to all Important for cell survival parts of the cells Fluid in nature ○ Kinesin (peripheral to center) Functions of cell membrane: ○ Dynein (away) ○ Separates cell from the extracellular environment ○ Myosin ○ Regulates the passage of substances into or out of cells (selective permeability) Gatekeeper LE 1 Trans 1 TG: BC, SC, LC, SC, KD, DL, CM, BM, NN, AS, RS, CT Page 4 of 7. ○ Restricts passage of some substances while permitting PHOSPHOLIPIDS/PHOSPHOGLYCERIDES the passage of others Maintains ionic gradient Most abundant cell membrane lipids ○ Difference in composition Amphipathic molecules Cell recognition via cell surface antigen ○ Polar head (water-soluble, hydrophilic): exposed on the Cell communication (chemical messengers) surface ○ Neurotransmitters ○ Two nonpolar hydrocarbon tails (hydrophobic): core of ○ Hormone receptors Enzymatic activity ○ ❗ the bilayer Amphipathic nature is critical for the formation of bilayer Determination of cell shape Tissue organization (linker proteins) Alcohol is attached to the phosphate Made up of saturated and unsaturated fats CELL MEMBRANE COMPOSITION Have kinks that prevents the molecules from associating closely with surrounding lipids Protein 50 - 55% ○ Unsaturated fats: double bond Phospholipids 25% ○ Saturated fats: no double bonds ○ ↑ kinks = ↑ fluidity Cholesterol 13% Majority of membrane of phospholipids have a glycerol backbone where fatty acyl chains are attached and an alcohol Other lipids 4% Carbohydrates 3% ❗ is linked to glycerol via a phosphate group ○ Exception: sphingomyelin (backbone is sphingosine) Table 2. Cell membrane composition and percentage Phospholipid Leaflet Location Backbone A. MEMBRANE LIPIDS Phosphatidylcholine Outer leaflet Glycerol Lipid bilayer with fluid-like properties Selective permeability Sphingomyelin Outer leaflet Sphingosine ○ Permeable to fat-soluble substances Phosphatidylethanolamine Inner leaflet Glycerol O2 CO2 Phosphatidylserine Inner leaflet Glycerol Alcohol ○ Impermeable to water-soluble substances Ions 👩‍⚕️Phosphatidylinositol (important for signal Inner leaflet Glycerol Glucose transduction) Urea Table 3. Types of phospholipids Amphipathic CHOLESTEROL ○ Phosphate head (hydrophilic, polar) ○ Fatty acid tail (hydrophobic, nonpolar) Amphipathic molecules Major lipids of the plasma membrane Sterol molecule ○ Phospholipids A major component of the plasma membrane ○ Sphingolipids ○ 50% of total membrane lipids ○ Cholesterol Located in both leaflets Fluidity is determined by: Mostly made up of saturated fats (no double bonds, no kink = ○ Temperature not fluid) ↑ temp = ↑ fluidity = ↑ permeability Stabilizes membrane at normal body temperature (37͒C) ○ Lipid composition Functions as “fluidity buffer” (affected by temperature and lipid ↑ unsaturated fatty acyl chains = ↑ fluidity composition. ↑ saturated fatty acyl chains = ↓ fluidity GLYCOLIPIDS Amphipathic molecules Less abundant; minor lipid component Sugar is attached instead of alcohol Has a kink Functions: ○ Receptor ○ Antigen Figure 4. Schematic diagram of the cell plasma membrane. ❗ MUST KNOW Fat-soluble substances can cross the lipid membrane Water-soluble substances cannot cross the lipid membrane; utilize proteins. LIPID RAFTS Aggregate of cholesterol and sphingomyelin Associated with specific proteins Functions: ○ Segregate signaling molecules (membrane protein trafficking) ○ Influence fluidity Figure 5. Types of cell membrane lipids LE 1 Trans 1 TG: BC, SC, LC, SC, KD, DL, CM, BM, NN, AS, RS, CT Page 5 of 7  B. MEMBRANE PROTEINS Cells must be able to: ○ Communicate with each other This is the reason why cells are organized ○ Stay bound to other cells and extracellular matrix Figure 6. Types of membrane proteins Figure 7. Types of membrane junctions INTEGRAL/INTRINSIC MEMBRANE PROTEINS A. TIGHT/OCCLUDING JUNCTIONS “Tagusan” or Tunnel-like ang appearance. Embedded in phospholipid bilayer (amphipathic) AKA zonula occludens Most span entire membrane (transmembrane proteins); others Cell-to-cell adhesion anchored to one of the monolayer Functions: Functions: ○ Strength and stability ○ Channels ○ Signaling role ○ Pumps ○ Example: Muscle cells – kaya sila dikit-dikit at di basta ○ G protein receptor basta napaghihiwalay. SANA ALL GORL!. Limit paracellular transport PERIPHERAL/EXTRINSIC MEMBRANE PROTEINS Requires transmembrane proteins “Nasa gilid” or “peripheral” ng integral or lipid-anchored ○ Occludins proteins ○ JAMs – Junctional Associated Molecules Anchored to carbohydrates ○ Claudins May associate with: ○ The polar group of membrane lipids B. ANCHORING/ADHERING JUNCTIONS ○ Functions: ○ 📖 Commonly bind to integral or lipid-anchored proteins Ion channels AKA zonula adherens Cell-to-cell and cell-matrix adhesion Important for: ○ Carriers ○ Maintenance of normal cell architecture and cell ○ Enzymes organization ○ Controllers of transport substances through the cell ○ Serve a signaling role during organ development and membrane "pores." remodeling. LIPID-ANCHORED MEMBRANE PROTEINS Connections: ○ Desmosomes (cell-cell) Mga proteins na nakakabit sa lipids ○ Focal adhesions and hemidesmosomes (cell-matrix) Covalently attached to a lipid molecule by lipid anchors Components: Associated with phosphatidylinositol ○ Formed by Ca++ dependent interaction of: ○ Signaling protein Intracellular anchor proteins “catenins” C. MEMBRANE CARBOHYDRATES site of attachment for intracellular actin. cytoskeleton Glycolipids and glycoproteins with covalently bound Integrins (cell-matrix) oligosaccharide chains Cadherins (cell-cell) Found only on the exterior Form the glycocalyx (sugar coating). GLYCOCALYX Give most cells an overall negative cell surface charge Attach cells to one another or cell to cell interaction (pavementing) ○ Ex. Pavementing in WBCs: during inflammation, WBCs adhere to endothelial cells (blood vessel epithelia) to enter inflamed tissue. Act as a receptor Some enter to immune reactions (as recognition molecules). EPITHELIAL STRUCTURES Contains epithelial cells arranged in sheets (external-internal environment) Functions: Figure 8. Types of anchoring junctions ○ Establish barrier to microorganism ○ Prevent loss of water C. GAP/COMMUNICATING JUNCTIONS ○ Maintenance of a constant internal environment AKA macula communicans Form cytoplasmic tunnels for diffusion of inorganic ions and MEMBRANE JUNCTIONS small molecules between 2 neighboring cells Cells are surrounded by extracellular fluid or matrix ○ Provide low-resistance connection (low pass filter) Some cells float free (RBC) Made up of connexons Most cells are organized and packaged together ○ Composed of connexin or pannexin protein subunits LE 1 Trans 1 TG: BC, SC, LC, SC, KD, DL, CM, BM, NN, AS, RS, CT Page 6 of 7  Electrical Synapse REVIEW QUESTIONS ○ Type of gap junction 1. The following are synthesized in which organelle of the cell: ○ Occurs between neurons, glial cells, cardiac, and unitary A. Neurotransmitters smooth muscle cells B. Insulin ○ Couple cells both electrically, chemically, and C. Estrogen metabolically ○ More permeable than membrane channels (mas malaki RATIONALE ang gap junctions) ❗PEMPHIGUS VULGARIS ANSWER: A. RER Characterized by the blistering of the skin and mucosa B. RER Problem in cadherins C. SER ○ Auto-antibodies bind to the intercellular junctions Neurotransmitters are made up of short sequences of (cadherins) in the epidermis amino acids (building blocks of proteins). ○ Cell loses its intracellular adhesion that connects Insulin is a peptide hormone secreted by the beta-cells of squamous epithelial cells (acantholysis) the pancreas. Estrogen is a steroid hormone synthesized from cholesterol. REFERENCES 2. Complete the table on cell membrane fluidity 1. Hall, J. E., & Hall, M. E. (2021). Functional Organization of the Human Body and Control of the “Internal Environment.” In TEMPERATURE FLUIDITY PERMEABILITY Guyton and Hall Textbook of Medical Physiology (14th ed., pp. 3–10). Elsevier. ↑ 2. Hall, J. E., & Hall, M. E. (2021). The Cell and Its Function. In Guyton and Hall Textbook of Medical Physiology (14th ed., pp. ↓ 13–28). Elsevier. 3. Powerpoint: Gomez, C. (2024). Cell Physiology (Structure and Function) 3. Blood glucose regulation is via the modified negative 4. Previous Trans: 2023 feedback mechanism, wherein: A. Increasing levels of glucose in the blood will stimulate the secretion of insulin bringing it back to normal B. Decreasing levels of glucose will decrease the secretion of glucagon, bringing it back to normal C. Decreasing levels of glucose in the blood will stimulate the secretion of insulin bringing it back to normal D. Increasing levels of glucose in the blood will decrease the secretion of insulin, bring it back to normal RATIONALE ANSWER: A An increased blood glucose will stimulate the beta cells of the pancreas to secrete insulin (the only hypoglycemic agent in the body). Increased insulin levels will result in increased uptake of glucose by the cells, thereby lowering the blood glucose levels in plasma. LE 1 Trans 1 TG: BC, SC, LC, SC, KD, DL, CM, BM, NN, AS, RS, CT Page 7 of 7  PHYSIOLOGY: LE1 | TRANS 02 CELL 2: CELL TRANSPORT CARIE GOMEZ, MD | 08/05/2024 OUTLINE I. Roles of plasma V. Transport through the membrane membrane II. Fluid compartments A. Passive transport III. Fluid concentration B. Active transport A. Tonicity VI. Transport across the B. Osmolarity membrane C. Osmolality A. Exocytosis IV. Membrane transport B. Endocytosis proteins VII. Epithelial transport A. Water channels C. Paracellular B. Ion channels D. Transcellular C. Solute Carriers D. ATP Dependent SUMMARY OF ABBREVIATIONS AQPs aquaporins NSS normal saline solution LEGENDS ❗ Must know 👩‍⚕️ Lecturer 📖 Book 🖥 Presentation 📝 Old Trans 𝑊𝑎𝑡𝑒𝑟 𝑐𝑜𝑚𝑝𝑜𝑠𝑖𝑡𝑖𝑜𝑛 = 𝑡𝑜𝑡𝑎𝑙 𝑏𝑜𝑑𝑦 𝑤𝑒𝑖𝑔ℎ𝑡 𝑥 𝑝𝑒𝑟𝑐𝑒𝑛𝑡 𝑐𝑜𝑚𝑝𝑜𝑠𝑖𝑡𝑖𝑜𝑛 LEARNING OBJECTIVES Solutes ○ 📝 Permeable Figure 1. Total body water At the end of the lecture, the student should be able to: ✔ Review about the cell membrane ✔ Differentiate osmolarity, osmolality, and tonicity ○ Impermeable Concentration of Solution ○ 📝 Concentration = Solute/Solvent ✔ Discuss fluid compartments Hypertonic =High=↑C =↑ Solute / ↓ Solvent ✔ Differentiate passive and active Transport Isotonic = Equal ✔ Discuss diffusion and osmosis Hypotonic=Low= ↓C= ↓Solute/ ↑Solvent ✔ Give the different factors that affect diffusion and osmosis ✔ Discuss vesicular transport ✔ Discuss epithelial transport FLUID CONCENTRATION Concentration 🖥 ROLES OF PLASMA MEMBRANE ○ Solutes Separates the cell from the extracellular environment Permeable selective permeability ○ 🖥 Regulates passage of substances into and out of cells Gatekeeper: restricts passage of some substances ○ Impermeable Solvent Water (universal) 🖥 while permitting the passage of others (semipermeable) Maintains difference in composition and establishes ionic Concentration of solution: 𝐶𝑜𝑛𝑐. 𝑜𝑓 𝑠𝑜𝑙'𝑛 = 𝑠𝑜𝑙𝑢𝑡𝑒 𝑠𝑜𝑙𝑣𝑒𝑛𝑡 compartments 🖥 gradient between the intracellular and extracellular Cell recognition via cell surface antigen 📝 A. OSMOLALITY Number of osmoles per kg of solvent receptors 📝 Cell communication through neurotransmitters and hormone ○ mOsm/kg of solvent Considers permeable and impermeable solutes chemical reactions (enzymatic activity) 📝 Determination of cell shape, tissue organization and carry out Not affected by volume and temperature Mass of water is difficult to measure Anchors to the protein Normal osmolality = 280 mOsm/Kg of H2O (isoosmolal) 𝑠𝑜𝑙𝑢𝑡𝑒 (𝑚𝑂𝑠𝑚) FLUID COMPARTMENTS 𝑂𝑠𝑚𝑜𝑙𝑎𝑙𝑖𝑡𝑦 = 𝑠𝑜𝑙𝑣𝑒𝑛𝑡 (𝑘𝑔) WATER COMPOSITION OF CELL B. OSMOLARITY ❗ MEMORY AID: 60:40:20:15:5 Number of osmoles per Liter of solution Water 60% ○ mOsm/L of solution Intracellular fluid Extracellular fluid 40% 20% Considers only permeable solutes Affected by volume and temperature, hence NOT stable Normal osmolarity = 280-300 mOsm/L (isoosmolar) 📝 ○ 0.9% NaCl solution (NSS) Interstitial fluid 15% ○ 5% Dextrose Plasma 5% 𝑠𝑜𝑙𝑢𝑡𝑒 (𝑚𝑂𝑠𝑚) 𝑂𝑠𝑚𝑜𝑙𝑎𝑟𝑖𝑡𝑦 = 𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛 (𝐿) ❗NOTE: Actual computation would be: LE 1 Trans 1 TG: BC, SC, LC, SC, KD, DL, CM, BM, NN, AS, RS, CT Page 1 of 5 EXTRACELLULAR FLUID ○ Highly selective or non-selective Interstitial and Intravascular fluid Na+: major determinant of ECF osmolarity (major extracellular C. SOLUTE CARRIERS cation) > 50 types (>400 specific transporters) ○ Uniporters (facilitated transporters) PLASMA OSMOLARITY COMPUTATION ○ Symporters (co-transporters) Simple equation: ○ Antiporters (counter-transporters or exchangers) 𝑃𝑙𝑎𝑠𝑚𝑎 𝑜𝑠𝑚𝑜𝑙𝑎𝑟𝑖𝑡𝑦 = (2)(𝑁𝑎) D. ATP-DEPENDENT TRANSPORTERS Accurate equation: Use ATP to move substances 𝐺𝑙𝑢𝑐𝑜𝑠𝑒 𝑈𝑟𝑒𝑎 Two types; 𝑃𝑙𝑎𝑠𝑚𝑎 𝑜𝑠𝑚𝑜𝑙𝑎𝑟𝑖𝑡𝑦 (𝑚𝑔/𝑑𝐿) = (2)(𝑁𝑎) + + 18 2.8 ○ ATPase ion transporters or P type 𝑃𝑙𝑎𝑠𝑚𝑎 𝑜𝑠𝑚𝑜𝑙𝑎𝑟𝑖𝑡𝑦 (𝑚𝑂𝑠𝑚/𝑘𝑔) = (2)(𝑁𝑎) + 𝐺𝑙𝑢𝑐𝑜𝑠𝑒 + 𝑈𝑟𝑒𝑎 V type F type C. TONICITY ○ ATP-binding Cassette (ABC) Describes the osmolality of a solution relative to plasma ○ Isoosmolal TRANSPORT THROUGH THE MEMBRANE ○ Isoosmolar 🖥 Considers only impermeable solutes PASSIVE TRANSPORT ACTIVE TRANSPORT Related to the effect of the solution on the volume of a cell ○ Isotonic- same Transport substances Transport substances ○ Hypertonic - greater along electrochemical against 🖥 ○ Hypotonic - lesser gradient electrochemical Example: Downhill movement gradient ○ 0.9% saline solution remains isotonic (no net movement (-) energy (ATP) Uphill movement and not metabolized) (-) carrier except (+) energy ATP ○ 5% glucose solution is isotonic when initially infused, but facilitated diffusion (+) carrier (-) net movement limitations: saturation eventually becomes hypotonic once equilibrium is kinetics, NICE-TO-KNOW: DIURETICS reached stereospecificity, Osmotic diuretic: only water is lost competitive inhibition Natriuretic: only sodium is lost Table 2. Passive vs. active transport 🖥 A. PASSIVE TRANSPORT DIFFUSION Random molecular movement of substances Figure 2. RBC in hypertonic, hypotonic, and isotonic solutions HYPOSMOTIC ISOSMOTIC HYPEROSMOTIC HYPOTONIC ✔ ✔ ✔ ISOTONIC ✔ ✔ HYPERTONIC ✔ Figure 3. Diffusion vs. active transport Table 1. Tonicity vs. osmotic environment Simple Diffusion Spontaneous process in which substances move from region MEMBRANE TRANSPORT PROTEINS Transporters (10% human genes) Requirements: 🖥 of higher concentration to lower concentration due to random motion (inherent kinetic energy) A. WATER CHANNELS AKA Aquaporins (AQPs) There are 12 aquaporins, widely distributed in isoforms 👩‍⚕️ ○ ○ Kinetic energy 🖥 Electrochemical gradient (driving force) Occur through interstices/watery channels 📖 📖 ○ Ex. AQP-2: antidiuretic hormone (ADH) Lipid-soluble gases and alcohols readily dissolve (O2 , N2 , Main route for water movement CO2 ) Water movement can be regulated by changing: ○ Number of AQPs with concentration of the diffusing substance 📖 Diffusion rate through open channel increases proportionately ○ ○ Permeability (gating) pH ❗ Diffusion 📝 Factors that affect diffusion rate are explained by Fick’s Law of B. ION CHANNELS ○ ○ Selective, inward or outward 👩‍⚕️ Widely distributed and are important in excitable cells ○ Classified by their selectivity, conductance and J = net rate of diffusion mechanism of channel gating D = diffusion coefficient LE 1 Trans 1 TG: BC, SC, LC, SC, KD, DL, CM, BM, NN, AS, RS, CT Page 2 of 5 A = area available for diffusion C = concentration difference across the membrane X = thickness of the membrane ○ σ = Osmotic coefficient (-) = movement occurs from higher to lower concentration ○ n = number of dissociable particles 👩‍⚕️ ○ C = total solute concentration Stokes-Einstein Equation ○ R = gas constant ○ T - temperature (Kelvin) ❗ 👩‍⚕️ MUST KNOW 👩‍⚕️👩‍⚕️ ↑ n = ↑ osmotic pressure ↑ C = ↑ osmotic pressure Diffusion Coefficient ○ ○ Oil/water partition coefficient (k) “lipid solubility” Molecular size (r) [radius] ↑ T = ↑ osmotic pressure Impermeable, ionizable = ↑ osmotic pressure Bigger solutes = ↑ osmotic pressure 👩‍⚕️ ○ Temperature (thermal energy) (T) ○ Viscosity of the medium (η) Permeability Coefficient ❗ Osmotic pressure generated by large molecules 🖥 ONCOTIC PRESSURE ○ Diffusion coefficient ○ Membrane properties ○ Ex. Proteins (albumin) 📖 ❗MUST KNOW Fluid movement across capillaries difference, lipid solubility, and temperature👩‍⚕️ Directly Proportional: diffusion coefficient, area, concentration Filtration medium👩‍⚕️ Inversely Proportional: thickness, molecular size, viscosity of hydrostatic gradient ○ 🖥 Substances and solvent move across the membrane driven by a Across capillaries/blood vessel membrane 👩‍⚕️ Solvent Drag Diffusion of Water Soluble Substances See appendix A. Usually happens in paracellular transport 👩‍⚕️ Facilitated Diffusion ○ 👩‍⚕️ When rapid movement of water occurs, solute gets dragged along from high to low concentration When carrier proteins move substances in the direction of B. ACTIVE TRANSPORT required ○ 📖 their chemical or electrical gradients, no energy input is Carrier mediated 📖 Transports substance against an electrochemical gradient with the use of ATP (uphill movement) ○ Example: glucose transport by the glucose transporter, ○ Concentration ○ Pressure from the ECF to the cytoplasm of the cell 📖 which moves glucose down its concentration gradient ○ Electrical All carrier mediated Diffusion rate approaches a maximum, called Vmax, as the concentration of the diffusing substance increases Limitations: 📖 ○ 📖 Carrier protein functions differently from the carrier in facilitated diffusion ○ ○ Saturation Specificity move it against the electrochemical gradient 📖 Capable of imparting energy to the transported substance to PRIMARY ACTIVE TRANSPORT phosphate 📖 Energy derived from ATP breakdown directly/high energy One or more substances 🖥 Directly linked to cellular metabolism ○ Directly uses ATP Transport substance against electrochemical gradient Examples: 🖥 ○ Na+K+ ATPase ○ Ca++ ATPase ○ H+K+ ATPase 🖥 SECONDARY ACTIVE TRANSPORT Linked to primary active transport indirectly ○ Uses ion concentration gradient established Figure 4. Rate of diffusion by primary active transport to fuel uphill Osmosis movement of substances Net Diffusion of water across a membrane 🖥 1 along gradient (primary active) ○ Passive movement of water across a semipermeable 🖥 Two or more substances 🖥 1 against gradient ○ Through aquaporins Requires: 🖥 membrane down its concentration gradient primary active transport 📖 Energy derived secondarily from stored energy, originally by ○ Concentration gradient for a solute across the membrane ○ Indirect utilization of ATP ○ Relative impermeability of membrane to the solute Co Transport ❗ OSMOTIC PRESSURE 🖥 📖 The gradient is the storehouse of energy (from primary active Amount of pressure required to stop movement of pure water into solution transport) ○ ○ Coupling mechanism by carrier protein 📖 Glucose and amino acids along with sodium ions 📖 Dependent on # of dissolved particles 🖥 Takes into account the ionization of the solute van’t Hoff’s law LE 1 Trans 1 TG: BC, SC, LC, SC, KD, DL, CM, BM, NN, AS, RS, CT Page 3 of 5  Counter Transport 📖 ○ 📖 Vesicles inside the cell fuse with the plasma membrane then ❗ release their contents Substance transported inside must be transported outside first ○ ○ Sodium-calcium countertransport Sodium hydrogen countertransport secretion)👩‍⚕️ Usually a Ca++-dependent process (except renin and PTH 👩‍⚕️ Constitutive (continuous release) or regulative (need stimulus) PRIMARY ACTIVE SECONDARY ACTIVE EPITHELIAL TRANSPORT 1 or more substances 2 or more substances Cellular sheet of movement 🖥 🖥 👩‍⚕️ all against one is alone while the Movement of substance across epithelial surface concentration rest are against Can be in between or through cell gradient indirect ATP utilization direct ATP utilization dependent on Primary A. PARACELLULAR can occur alone uses all types of Active Transport only uses co transport Occurs in between two adjacent cells Limited by tight junctions 🖥 transporters and anti transport 👩‍⚕️ ○ Primarily transport ions and water Table 3. Primary active vs. secondary active transport ○ Small area for diffusion Solvent drag TRANSPORT ACROSS THE MEMBRANE B. TRANSCELLULAR Movement of large substances across but not through the membrane Vesicular transport 🖥 👩‍⚕️ Across or through the cell (either from apical or basolateral) ○ Via vesicle formation (detach from/fuse with plasma membrane) ○ Polarized Passing the apical and basolateral membrane ○ Na+K+ ATPase in basolateral membrane 🖥 ○ Plasma membrane integrity maintained ○ Fuels secondary transport of nutrients in apical membrane A. ENDOCYTOSIS ○ Ingestion by a cell ○ 📖 Obtain nutrients and substances from surrounding fluids REFERENCES 1. PhD, J. H. E., & MSc., M. M. H. E. (2020). Guyton and Hall Textbook of Medical Physiology (Guyton Physiology) (13th ed.). ○ Large particles enter cell Elsevier. ○ Principal forms: 2. B. (2022). Ganong’s Review Medical Physiology 26e. Mc Graw pinocytosis and phagocytosis Hill Education (Uk). Moves substances (water and solute) into the cell 3. Md, B. K. M., PhD, & PhD, B. S. A. (2017). Berne & Levy PINOCYTOSIS Physiology (7th ed.). Elsevier. Cell drinking ○ 🖥 Non specific transport of small molecules into cell 4. Powerpoint: Gomez, C. (2022). Cell Physiology (Structure and Function) Prominent feature observed across capillaries 5. Previous Trans: 2022, 2023 Often begin at clathrin coated proteins REVIEW QUESTIONS Ex. ECF, soluble material PHAGOCYTOSIS 1. Which vesicular transport process occurs primarily in Cell eating ○ 🖥 Transport of large molecules or particulate material into the some white blood cells and macrophages? A. exocytosis B. phagocytosis cell C. pinocytosis Important immune system feature D. intracellular vesicular trafficking Often receptor mediated Ex. Bacteria, dead tissue, cell debris RATIONALE ANSWER: B TYPES OF ENDOCYTOSIS Receptor Mediated ○ 🖥 Specific receptor-substrate complex Phagocytosis is a complex process of ingestion and elimination of pathogens. They are monocytes, macrophages, neutrophils, dendritic cells, Specific substance into the cell osteoclasts, and eosinophils. Binding of substance with specific receptor ○ Requires accessory proteins 2. A physiologist observes that the concentration of sodium ○ cell membrane “coated pits” adaptin 📖 Receptors concentrated in small pits on outer surface of inside a cell is decidedly lower than that outside the cell. Sodium diffuses easily across the plasma membrane of such cells when they are dead, but not when they are clathrin alive. What cellular function that is lacking in dead cells GTPase dynamin explains the difference? Clathrin Mediated ○ 🖥 Involves clathrin accumulation A. osmosis B. diffusion ○ May/may not require dynamin C. active transport (solute pumping) ○ Synaptic functions D. dialysis ○ Ex. nerve factor Caveolae Mediated ○ Rafts 🖥 RATIONALE ANSWER: C ○ Caveolae formation (caveolin) The Na+ K+-ATPase pump maintains the gradient of a higher concentration of sodium extracellularly and a B. EXOCYTOSIS higher level of potassium intracellularly. The Ejection or secretion of molecules from cell ○ Reverse endocytosis 🖥 sustained concentration gradient is crucial for physiological processes in many organs and has an Membrane-bound ongoing role in stabilizing the resting membrane LE 1 Trans 1 TG: BC, SC, LC, SC, KD, DL, CM, BM, NN, AS, RS, CT Page 4 of 5  potential of the cell, regulating the cell volume, and RATIONALE cell signal transduction ANSWER: B In a hypertonic solution, the net movement of water 3. The term used to describe the type of solution in which will be out of the body and into the solution. A cell cells will lose water to their environment is: placed in a hypertonic solution will shrivel and die by A. isotonic a process known as plasmolysis. B. hypertonic C. hypotonic D. catatonic APPENDIX Appendix A: Decreasing permeability LE 1 Trans 1 TG: BC, SC, LC, SC, KD, DL, CM, BM, NN, AS, RS, CT Page 5 of 5