SAN BEDA COLLEGE OF MEDICINE CELL AND MOLECULAR PHYSIOLOGY HANDOUT BY HOWELL D. CRISOSTOMO, MD 1.

1 CELLULAR AND MOLECULAR PHYSIOLOGY Howell D. Crisostomo, MD hdcrisostomo@post.upm.edu.ph 0917-583-4955 | 0932-665-6688 hdcrisostomo@icloud.com CELL AND MOLECULAR PHYSIOLOGY EDUCATIONAL OBJECTIVES At the end of the 4-hour lecture, the future Bedan Doctor must be able to: Define homeostasis. Differentiate the control mechanisms of body functions. Nervous control Hormonal control Describe the composition of the different body fluid compartments. Describe the components of the cell with their corresponding functions. Describe the fluid-mosaic model of membranes in general. Discuss the functions of the different components of a cell. Nucleus Endomembrane system and intracellular vesicular traffic Ribosomes and protein synthesis Mitochondria and energy conversion Cytoskeleton

Intracellular

Extracellular

I am 70 kg man, how much of me is extracellular? TBW = 0.6 x 70 kg = 42 L ICF = 0.4 x 70 kg = 28 L ECF = 0.2 x 70 kg = 14 L IF = 0.75 x 14 L = 10.5 L Plasma = 0.25 x 14 L = 3.5 L Regulation of Body Functions Nervous Systems Input (Sensory) Integrative (CNS) Output (Motor) Autonomic Hormone System Immune System NERVOUS CONTROL HORMONAL CONTROL

Homeostasis

Maintenance of nearly constant conditions in the internal environment Ability to maintain stable internal environment The goal of all physiologic processes Variables are physiologically controlled (usually via negative feedback) Each cell, tissue and organ system play a role. Its all about balance

PARAMETER Reaction Time Mediators Type of Message Response Target milieu intrieur The internal environment for our TRILLIONS of cells. A 70 kg man is approximately composed up of 42 liters of water. Intracellular and extracellular fluid 2/3 are intracellular 1/3 are extracellular Extracellular fluid maintains the internal environment or milieu intrieur Linking Mechanism Effectors Function

White blood cells Lymphoid tissues distinguish its own cells from foreign cells and substances

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SAN BEDA COLLEGE OF MEDICINE CELL AND MOLECULAR PHYSIOLOGY HANDOUT BY HOWELL D. CRISOSTOMO, MD destroy the invader by phagocytosis or by producing sensitized lymphocytes or specialized proteins Integumentary System boundary between the body's internal environment and the outside world temperature regulation and excretion of wastes Gain of Control System The degree of effectiveness with which a control system maintains constant condition Used by the CNS to determine if a certain muscle contraction/movement is performed correctly A form of delayed negative feedback

Examples of negative feedback mechanism: 1. 2. Examples of positive feedback mechanisms: 1. 2.

THE CELL Example: A patient without an intact baroreceptor reflex was transfused with 200 mL of blood. His blood pressure is normally 100 mm Hg and increased to 175 mm Hg after transfusion. The same amount of blood is transfused to another individual with an intact baroreceptor reflex. His blood pressure from 100 mm Hg increased to only 125 mm hg. Without control(without a baroreceptor): 100 to 175 = 75 increase With control (with an intact baroreceptor) 100 to 125 = 25 increase Thus, we can say that the baroreceptor reflex has caused a correction of -50: 175 mm Hg 125 mm Hg = -50 mm Hg If we consider that an intact system would control 50 mm Hg, that leaves 25 mm Hg in the patient without a baroreceptor as an error figure Thus, the gain of the baroreceptor system in this example is _____ What does this mean? _____________________________________________ Typical Set Point Value Basic unit of life All organisms are made up of cells A highly dynamic entity Principle of Biogenesis does this still apply today and in the near future? ORGANIZATION OF THE CELL Water 70-85% percent for most cells Ions potassium, magnesium, phosphate, sulfate, bicarbonate Proteins 10 to 20 percent of cell mass Structural Functional Lipids Membranes Carbohydrates Protoplasm collective term for different substances that make up the cell composed mainly of five basic substances: WATER ELECTROLYTES PROTEINS LIPIDS CARBOHYDRATES Water principal fluid medium of the cell present in most cells, except for fat cells, in a concentration of 70 to 85 percent Electrolytes / Ions inorganic chemicals for cellular reactions necessary for operation of some of the cellular control mechanisms Important ions in the cell include potassium, magnesium, phosphate, sulfate, bicarbonate, sodium, chloride, calcium Proteins constitute 10 to 20 percent of the cell mass can be classified into: STRUCTURAL PROTEINS FUNCTIONAL PROTEINS Structural Proteins long intracellular filaments that form microtubules and fibrillar proteins EXAMPLES cytoskeleton of cellular organelles fibrillar proteins in collagen and elastin fibers Functional Proteins composed of combinations of a few molecules in tubular-globular form EXAMPLES: Enzymes substances that catalyze specific intracellular

Controlled Variable Arterial O2 Partial Pressure Arterial CO2 Partial Pressure Arterial Blood pH Glucose Core Body Temperature Serum Na+ Serum K+ Serum Ca2+ Mean Arterial Blood Pressure Glomerular Filtration Rate Feedback Mechanisms

Most are ______________ in nature the output shuts off the original effect of the stimulus or reduces its intensity Some positive feedback mechanisms: Blood clotting Nerve signaling Child birth Feed-forward control Also known as adaptive control

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SAN BEDA COLLEGE OF MEDICINE CELL AND MOLECULAR PHYSIOLOGY HANDOUT BY HOWELL D. CRISOSTOMO, MD Lipids soluble in fat solvents but insoluble in water EXAMPLES: PHOSPHOLIPIDS AND CHOLESTEROL 2% of total cell mass forms the cell membrane and membrane barriers TRIGLYCERIDES (neutral fat) in fat cells, constitutes 95% of the cell mass storehouse of energy-giving nutrients Carbohydrates little structural function in the cell except as parts of glycoprotein molecule play a major role in cellular nutrition EXAMPLES glucose glycogen CELLULAR ULTRASTRUCTURE Many organelles of the cells are covered by membranes composed primarily of lipids and proteins cell membrane, nuclear membrane, membrane of the endoplasmic reticulum, and membranes of the mitochondria, lysosomes, and Golgi apparatus receptors G proteins Target of many disease processes and DRUGS!

Peripheral Proteins not embedded in the cell membrane are not covalently bound to membrane components loosely attached to the cell membrane by electrostatic interactions

Cell Membrane Thin, pliable, elastic structure 7.5 to 10 nanometers thick composition is proteins, 55 percent; phospholipids, 25 percent; cholesterol, 13 percent; other lipids, 4 percent; and carbohydrates, 3 percent. Mostly proteins and lipids Fluid Mosaic Model conceptualizes that the cell membrane is composed of a ______________________________ proteins and other substances are embedded in the phospholipid bilayer

Glycocalyx loose carbohydrate coat of the cell membrane carbohydrates in combination with proteins (glycoproteins) or lipids (glycolipids) proteoglycans are carbohydrate substances bound to small protein cores functions of the glycocalyx include: imparts a ___________ electrical charge attachment to glycocalyx of other cells receptor substances for binding hormones immune reactions Other Membrane Lipids cholesterol molecules are dissolved in the bilayer of the membrane functions of cholesterol: determine the degree of permeability of the bilayer to water-soluble constituents controls much of the fluidity of the membrane Cellular Organelles specialized cellular subunit found in the cytoplasm that has a specific function usually membrane-bound Cytoskeleton fibrillar proteins synthesized by ribosomes in the cytoplasm function is to provide rigid physical support for certain parts of cells (intracellular scaffolding) EXAMPLES: filaments: actin filaments in cytoplasm, actin and myosin filaments in muscles _________________: flagellum in sperm, cilia in respiratory tract, centrioles, mitotic spindle Mitochondria also called the powerhouse of the cell forms _________________________ used for membrane transport, synthesis of chemicals and mechanical work unique characteristics: self-replicative because it contains its own DNA found in the mitochondrial matrix has its own genetic code mitochondrial DNA is ___________derived Endoplasmic Reticulum network of tubular and flat vesicular structures in the cytoplasm space inside the tubules and vesicles is filled with endoplasmic matrix

Parts of the Cell Membrane Phospholipid bilayer Membrane proteins Membrane carbohydrates (glycocalyx) Other membrane lipids Phospholipid Bilayer phosphate end of each phospholipid soluble in water (hydrophilic end) fatty acid end soluble only in fats (hydrophobic end) repelled by water but are mutually attracted to one another natural tendency to attach to one another in the middle of the membrane possession of both hydrophilic and hydrophobic properties make phospholipids amphipathic molecules Integral Proteins anchored and embedded in the cell membrane through -________________ interactions may span the cell membrane (transmembrane proteins) EXAMPLES: ion channels transport proteins

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SAN BEDA COLLEGE OF MEDICINE CELL AND MOLECULAR PHYSIOLOGY HANDOUT BY HOWELL D. CRISOSTOMO, MD space inside the endoplasmic reticulum is connected with the space between the two membrane surfaces of the nuclear membrane machinery for a major metabolic functions of the cell Nuclear Membrane also called nuclear envelope two separate bilayer membranes outer membrane is continuous with the endoplasmic reticulum of the cell cytoplasm penetrated by several thousand nuclear pores large complexes of protein molecules are attached allow molecules up to 44,000 molecular weight to pass through with reasonable ease

Rough Endoplasmic Reticulum also called _______________ endoplasmic reticulum large numbers of ribosomes are attached to the outer surfaces of the RER minute granular particles composed of a mixture of RNA and proteins function in protein synthesis not all ribosomes in a cell are bound to the RER _______________ Endoplasmic Reticulum also called agranular endoplasmic reticulum has no attached ribosomes functions include: detoxification of substances synthesis of lipids found in great quantities in the liver and kidneys Golgi Apparatus closely related to the endoplasmic reticulum composed of four or more stacked layers of thin, flat, enclosed vesicles lying near one side of the nucleus functions include: _______________ of proteins molecular __________________ prominent in secretory cells Lysosomes vesicular organelles that form by breaking off from the Golgi apparatus intracellular digestive system for damaged cellular structures, food particles and bacteria filled with large numbers of small enyme granules (hydrolase, lysozyme, lysoferritin) called suicide bags of cells binding of calcium ions triggers apoptosis once the lysosomes have completed their function Peroxisomes differences with lysosomes formed by self-replication or budding off from SER contain ______________ and __________ enzymes functions include: oxidizes many poisonous substances degrades free radicals that may damage cells Secretory Vesicles also called secretory granules formed by the ER-Golgi apparatus system functions include storage for enzymes that are not yet activated (proenzymes) replenish the plasma membrane whenever it forms phagocytic or pinocytic vesicles Nucleus control center of the cell contains large quantities of DNA (genes) on microscopy, DNA is seen as darkly staining chromatin material genes are duplicated during mitosis during mitosis, chromatin organizes into highly structured chromosomes almost all nucleated cells in the body contain the same set of chromosomes and DNA SAN BEDA COLLEGE OF MEDICINE Page 4 of 4 PHYSIOLOGY HANDOUT BY HOWELLDC, MD

Nucleolus unlike most other organelles, does not have a limiting membrane accumulation of large amounts of RNA and ribosomal proteins becomes considerably enlarged when the cell is actively synthesizing proteins Organelle Assembly factory

Taxi Power plant cytoskeleton ASSIGNMENT: What is the Human Genome Project? When was this completed? What is/are the implications of genomics in medicine?

SOURCES: 1. Guyton & Hall Textbook of Medical Physiology 12th Edition by Hall, John &, Guyton, Arthur C. , , Published in Philadelphia, Pensylvania: Saunders/Elsevier, 2011 2. Berne & Levy Physiology 6th Edition bby Berne, Robert M., 1918-2001., Koeppen, Bruce M., Published: Philadelphia : Mosby/Elsevier, 2008 3. Ganong Review of Medical Physiology, 23rd Edition, by Barrett, Kim , Barrett, Kim E., Barman, Susan, Boitano, Scott, Brooks, Heddwen, Published: New York : McGraw-Hill Medical, 2010 4. BRS Physiology 5th Edition by Linda Constanzo, 2011, Published: Lippincott and Williams & Wilkins 5. Kaplan Medical Step 1 Lecture Notes (Physiology) 2010 6. Medical Physiology: Big Picture by By (author) Jonathan Kibble, Colby Halsey, Published: Lange 7. Harpers Illustrated Biochemistry 27th Edition by Murray, Robert K. by Lange 8. Basic and Clinical Pharmacology 11th Edition by by Katzung, Bertram G. , Published: New York : McGraw-Hill Medical, 2009 9. SBCM Physiology Lectures 10. Various Internet Websites