Topnotch Medical Board Prep Physiology Main Handout (October 2022) PDF

TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA For inquiries visit www.topnotchboardprep.com.ph or https://www.facebook.com/topnotchmedicalboardprep/ This handout is only valid for Octo...

TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA For inquiries visit www.topnotchboardprep.com.ph or https://www.facebook.com/topnotchmedicalboardprep/ This handout is only valid for October 2022 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly. MODULE PAGE 1. Cell and Muscle Physiology 1 IMPORTANT LEGAL INFORMATION 2. Neurophysiology 14 3. Cardiovascular Physiology 30 The handouts, videos and other review materials, provided by Topnotch Medical Board Preparation Incorporated are duly protected by RA 8293 otherwise known as the Intellectual 4. Respiratory Physiology 42 Property Code of the Philippines, and shall only be for the sole use of the person: a) whose 5. Renal & Acid-base Physiology 54 name appear on the handout or review material, b) person subscribed to Topnotch Medical 6. Gastrointestinal Physiology 65 Board Preparation Incorporated Program or c) is the recipient of this electronic 7. Endocrine and Reproductive Physiology 74 communication. No part of the handout, video or other review material may be reproduced, shared, sold and distributed through any printed form, audio or video recording, electronic 8. Hematology and Special Environments Physiology 87 medium or machine-readable form, in whole or in part without the written consent of Topnotch Medical Board Preparation Incorporated. Any violation and or infringement, whether intended or otherwise shall be subject to legal action and prosecution to the full 1. CELL & MUSCLE PHYSIOLOGY extent guaranteed by law. 1. Cell Membranes 2. Transport Across Cell Membranes DISCLOSURE 3. Osmosis The handouts/review materials must be treated with utmost confidentiality. It shall be the 4. Diffusion Potential, Resting Membrane Potential, Action Potential responsibility of the person, whose name appears therein, that the handouts/review 5. Neuromuscular and Synaptic Transmission materials are not photocopied or in any way reproduced, shared or lent to any person or disposed in any manner. Any handout/review material found in the possession of another 6. Skeletal Muscles person whose name does not appear therein shall be prima facie evidence of violation of RA 7. Cardiac Muscles 8293. Topnotch review materials are updated every six (6) months based on the current 8. Smooth Muscles trends and feedback. Please buy all recommended review books and other materials listed 9. Comparison of Skeletal Muscles, Smooth Muscles and Cardiac Muscles below. THIS HANDOUT IS NOT FOR SALE! 1.1 CELL MEMBRANES INSTRUCTIONS CELL To scan QR codes on iPhone and iPad 1. Launch the Camera app on your IOS device basic unit of the human body 2. Point it at the QR code you want to scan 3. Look for the notification banner at the top CELL NUMBER of the screen and tap Approximate number of human cells + bacterial To scan QR codes on Android 68 trillion 1. Install QR code reader from Play Store cells inside the human body 2. Launch QR code app on your device Approximate number of human cells (80% are 3. Point it at the QR code you want to scan 30 trillion 4. Tap browse website RBCs – most abundant type of cell in the body) 1 trillion Approximate number of glial (supporting) cells Approximate number of neurons (actual value A PRAYER FOR EXAMS 100 billion closer to 86B) TO ST. JOSEPH OF Remember: major hallmarks of cancer: loss of cell-to-cell adhesion and CUPERTINO (optional) anchorage independent growth https://qrs.ly/uddpcbx Dr. Banzuela CELL MEMBRANE The Guardian of the Cell: divides the body into extracellular fluid Approach to Topnotch Physiology (ECF) and intracellular fluid (ICF) compartments Please buy the following: Physio BRS 6th ed and Ganong Contains many protein, little carbohydrates, no water Physiology 23rd ed or 25th ed, and Pre-Test Physiology 14th Ed Semipermeable o To be used as major reference books Has variable composition throughout the life of the cell o they’re very good books that will help you in this subject o Lecture utilizes mainly Physio BRS supplemented by other Made up of a Lipid Bilayer (Fluid-Mosaic Model) sources (e.g. Guyton, Berne and Levy, Ganong); those that you o 55%: Proteins don’t understand or need further discussion, refer to Physio BRS o 25%: Phospholipids and Ganong § Outer Leaflet: Phosphatidylcholine, Sphingomyelin, § Inner Leaflet: Phosphatidylethanolamine, We won’t try to cover all of physio; we’ll try to cover: Phosphatidylserine, Phosphatidylinositol o What you need as a General Physician (must-knows) o 13%: Cholesterol: confers membrane fluidity and permeability o Less important topics that has been asked in the past (nice-to- to water-soluble substances knows) § major lipoprotein source of cholesterol: LDL Guided highlighting system: highlight only those that are bold o 4%: Other lipids: glycolipids confer antigenicity and italicized → we’ve identified them for you o 3% Carbohydrates This handout is only for the one whose name appears as a watermark. Videos are only for enrolled students. Handouts will Remember: cell membrane lets hydrophobic/fat-soluble substances to move in or out of the cell membrane with ease according to concentration expire October 2022. gradient. Imagine oxygen, carbon dioxide and steroid hormones directly penetrating the cell membrane. The lipid bilayer basically allows fat- This handout is only valid for the October 2022 PLE batch. soluble substances to move across it. This will be rendered obsolete for the next batch Dr. Banzuela since we update our handouts regularly. Factors that determine permeability of the cell membrane o Temperature o Types of solutes present MEDICAL PHYSIOLOGY o Level of cell hydration By Enrico Paolo C. Banzuela, MD, MSEd, MHPEd, FPSP Studded with the following proteins: University of the Philippines College of Medicine Class 2005 o Integral Proteins Master in Educational Entrepreneurship (MSEd), University of Pennsylvania Graduate § Has tight attachment (needs detergent to remove) using School of Education hydrophobic interactions Master in Health Professions Education (MHPEd), University of the Philippines Manila, § spans the entire cell membrane National Teacher Training Center for the Health Professions Master of Health Professions Education (MHPE), University of Maastricht (current § e.g. Aquaporins, Ion Channels, Solute Carriers (GLUT, student) Symport, Antiport), ATP-dependent Transporters Management Development Program, Asian Institute of Management o Peripheral Proteins Postgraduate Certificate in Teaching Evidence-Based Healthcare, University of Oxford Program for Leading Innovations in Health Care and Education, Harvard Macy Institute § Has loose attachment using electrostatic interactions (incoming student 2022) § Found in the inner leaflet or outer leaflet Course Coordinator (Chairman) for Physiology, San Beda University College of Medicine Associate Professor II, San Beda College of Medicine Guest Lecturer, Ateneo School of Medicine & Public Health Physiology Teacher, Topnotch Medical Board Prep Co-Author, IM Platinum, Surgery Platinum, Pedia Platinum, and OB-GYN Platinum Vice-President, Philippine Society of Physiologists (PSP) Fellow, Philippine Society of Physiologists (PSP) TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA Page 1 of 97 For inquiries visit www.topnotchboardprep.com.ph or email us at [email protected] This handout is only valid for October 2022 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.  TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA For inquiries visit www.topnotchboardprep.com.ph or https://www.facebook.com/topnotchmedicalboardprep/ This handout is only valid for October 2022 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly. © Topnotch Medical Board Prep Look at the picture above. The integral proteins are TIGHTLY-attached and do not move. The peripheral proteins are loosely-attached and tend to “float” in the lipid bilayer – like leaves or flowers floating in a pond. Viewed externally – those peripheral proteins floating around gives the cell a © Topnotch Medical Board Prep “mosaic” appearance, giving rise to the term “fluid-mosaic model” Dr. Banzuela Movement of different substances across the cell membrane: o Water § Undergoes Osmosis via Aquaporins o Lipid-Soluble (Non-polar, Hydrophobic) Substances § Substances undergo Simple Diffusion o Water-Soluble (Polar, Hydrophilic) Substances § Substances undergo Carrier-mediated Transport © Topnotch Medical Board Prep INTERCELLULAR STRUCTURES BETWEEN CELL MEMBRANES TYPE DESCRIPTION LOCATION NOTES Macula Adherens Disk-shaped; Epithelium Like intercellular stapler wires (Desmosomes) For tight intercellular adhesion Epithelial & endothelial cells Equivalent in cardiomyocytes is Fascia Ring-shaped Zonula Adherens Intercalated disks of cardiac Adherens (ribbon-like patterns; doesn’t increases surface area for contact muscles completely enclose cell) Transcellular Transport: movement Barrier to movement of proteins Leaky: PCT, Jejunum Zonula Occludens across apical and basolateral sides across membranes; divides cell into Tight: CD, terminal Colon, (Tight Junctions) Paracellular Transport: movement apical and basolateral side BBB through TJ bridge for sharing of small Cardiac and unitary smooth Functional Unit: ConneXON (its Subunit: Gap Junctions molecules between cells; For rapid muscles ConneXIN) intercellular communication When you hear desmosomes, think STAPLER wires – they hold cells TYPE MOVEMENT EXAMPLES together in tight attachment. They make cells ADHERE to each other – II. CARRIER-MEDIATED TRANSPORT kaya tinatawag din siyang Macula ADHEREns. Gap Junctions – they enable the cells to contract together as one. When you hear gap junctions, think Osmosis L conc →H conc Water SYNCYTIUM – the ability of muscle cells to contract together as one. H conc → L conc Facilitated GLUT transporters, Stratum Basale/Germinativum is separated from the dermis by the (Passive; Diffusion AA transporters basement membrane (basal lamina) and attached to the basement Downhill) membrane by HEMIDESMOSOMES. Na+-K+-ATPase Bind adhesion proteins to the cytoskeleton within cardiac myocytes, thus pump, connecting the cells: DESMOSOMES INSIDE INTERCALATED DISCS H+-K+ ATPase pump Dr. Banzuela of the parietal cells (stomach), ✔GUIDE QUESTION The low-resistance pathways between myocardial cells that allow for the H+-ATPase pump in spread of action potentials are the Primary Active L conc → H conc intercalated cells (A) gap junctions Transport (Active; Uphill) (kidneys) (B) T tubules Ca2+-ATPase pump (C) sarcoplasmic reticulum (SR) in the cell membrane (D) intercalated disks & SR, (E) mitochondria Costanzo LS. BRS Physiology. 6 ed. 2014. th multi-drug resistance 1.2 TRANSPORT ACROSS CELL MEMBRANES transporters SGLT-1 in the S.I. SGLT-2 in the PCT CELL TRANSPORT Na2+-K+-2Cl- in TAL https://qrs.ly/r5dpcbz Secondary L conc → H conc of LH Active (Active; Uphill) Na-Ca2+ exchange in Transport almost all cells Refer to this audio file while reading this very important table. Dr. Banzuela Na+-H+ exchange in the PCT (kidneys) TYPE MOVEMENT EXAMPLES I. NON- CARRIER MEDIATED TRANSPORT SPECIAL NOTES: SIMPLE DIFFUSION Oxygen, Nitrogen, CO2, Measured using the formula: Simple H conc → L conc alcohol, lipid 𝑱 = 𝑷𝑨 × (𝑪𝟏 − 𝑪𝟐 ) Diffusion (Passive; Downhill) hormones, anesthetic J = flux (flow (mmol/sec) drugs P = permeability (cm/sec) Divided in Pino- and A = area (cm2) Phagocytosis C1 = higher concentration 1 (mmol/L) Endocytosis - C2 = lower concentration 2 (mmol/L) e.g., Neutrophils and Bacteria Exocytosis - Hormones and NTs TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA Page 2 of 97 For inquiries visit www.topnotchboardprep.com.ph or email us at [email protected] This handout is only valid for October 2022 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.  TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA For inquiries visit www.topnotchboardprep.com.ph or https://www.facebook.com/topnotchmedicalboardprep/ This handout is only valid for October 2022 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly. SPECIAL NOTES: FACILITATED DIFFUSION At low-solute concentrations: Facilitated Diffusion is faster than Simple diffusion (because FD involves carrier proteins, which makes it go faster, analogous to a person riding a fast car) At high-solute concentrations: Facilitated Diffusion is slower than Simple Diffusion (because FD exhibits saturation and transport maximum (basically a speed limit), unlike SD) GLUT 1 Blood-brain barrier, RBCs, Cornea, Placenta Liver, Pancreas (β islet cells), Basement Membrane GLUT 2 of Small Intestine, Kidney GLUT 3 Neurons, Placenta Muscles, Adipose (only insulin-dependent glucose GLUT 4 transporter) For fructose transport from SI lumen to SI cell, GLUT 5 Spermatocytes (fructose is the energy source for sperm motility) © Topnotch Medical Board Prep When we place formulas in the handout, it means they are important. Look at the formula above. Memorize these formulas. Dr. Banzuela P (permeability) in the formula J= PA (C1-C2) is increased by the following: o Increased Oil / water partition coefficient of solute (increases solubility in the lipid of the membrane) o Decreased Radius of solute o Decreased Membrane Thickness Small Hydrophobic Solutes (O2, CO2): high permeability Hydrophilic Solutes (Na, K): uses aquaporins or transporters to © Topnotch Medical Board Prep cross cell membrane Most important characteristic of hydrophobic hormones that GLUT TRANSPORTERS governs diffusion across cell membrane: Lipid Solubility MNEMONIC Take note of the formula for simple diffusion (J=PA(C1-C2), and the factors https://qrs.ly/5sdpcc5 that will increase permeability – increased oil/water partition coefficient of the solute, small size, thin membrane. You need that to answer the guide SPECIAL NOTES: PRIMARY ACTIVE TRANSPORT question below: Dr. Banzuela Exhibits co-transport (“symport”) and Countertransport (“anti- ✔GUIDE QUESTIONS port” or “exchange”) Which of the following will double the permeability of a solute in a lipid Source of energy: ATP hydrolysis bilayer? Na+-K+ ATPase Pump (A) Doubling the molecular radius of the solute o 3 Sodium Out, 2 Potassium In (Mnemonic: “TRI-NA TO-K-EN”) (B) Doubling the oil/water partition coefficient of the solute o Keeps Na+ in the ECF and K+ in the ICF (C) Doubling the thickness of the bilayer o Contributes to RMP (-4mv out of the -70mv) (D) Doubling the concentration difference of the solute across the o Contributes to Basal Metabolic Rate (BMR) bilayer 1-19 Costanzo LS. BRS Physiology. 7 ed. 2019. th Solutions A and B are separated by a membrane that is permeable to o Some cardiac Na+-K+-ATPase pump inhibited by Digoxin urea. Solution A is 10 mM urea, and solution B is 5 mM urea. If the o Found in the basement membrane side except for Choroid concentration of urea in solution A is doubled, the flux of urea across Plexus the membrane will Ca2+-ATPase pump in the sarcoplasmic reticulum: SERCA (A) double o SERCA pumps Ca2+ back to the SR (B) triple H+-K+-ATPase pump in the lumen of the parietal cells of the (C) be unchanged stomach: Proton Pump (D) decrease to one-half (E) decrease to one-third 1-11 Costanzo LS. BRS Physiology. 7 ed. 2019.th For the guide question above: J1 = PA (C1-C2) =PA (10-5) = 5 J2 = PA (C1-C2) = PA (20-5) = 15 J2 is 3x more than J1. Kaya “triple” yung sagot. Remember: flux of urea is from high concentration to low concentration since urea undergoes simple diffusion. Dr. Banzuela SPECIAL NOTES: CARRIER-MEDIATED TRANSPORT Important Characteristics: o Stereospecificity: Two substances may have the same chemical composition, but different “shape”. Carriers accommodate a © Topnotch Medical Board Prep specific “shape” (e.g., D-glucose vs. L-glucose) Remember:” basta may ATP sa name, Primary yan.” o Saturation: number of carriers are finite. Once all carriers are Dr. Banzuela filled up or saturated, rate of transport becomes constant SPECIAL NOTES: SECONDARY ACTIVE TRANSPORT (Transport Maximum) Exhibits co-transport (“symport”) and Countertransport (“anti- o Competition: different solutes may compete for same carrier port” or “exchange”) (e.g., Gal vs. Glu in the SGLT-1 of small intestine) Source of Energy: downhill transport of Na+ (indirectly relies on o SGLT-1 Deficiency in newborns lead to glu/gal malabsorption Na+-K+-ATPase pump) leading to severe diarrhea Remember:” basta may sodium sa name, Secondary yan.” Dr. Banzuela Remember the properties of Carrier-Mediated Transport: S-S-C – Co-Transport (Symport): solutes move in same direction stereospecificity, saturation and competition. May shape lang na pwedeng gumamit ng carrier protein (stereospecificity), limited and Countertransport (Antiport, Exchange): solutes move in number ng carrier protein (saturation), at pwedeng magkaroon ng opposite directions competition for the carrier proteins (competition: parang “Trip to Sodium-Glucose Cotransport (SGLT) Jerusalem”). o Na+ moves downhill, Glu moves uphill, both move in the same Dr. Banzuela direction (Cotransport) o SGLT-1: SI, SGLT-2: Kidneys TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA Page 3 of 97 For inquiries visit www.topnotchboardprep.com.ph or email us at [email protected] This handout is only valid for October 2022 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.  TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA For inquiries visit www.topnotchboardprep.com.ph or https://www.facebook.com/topnotchmedicalboardprep/ This handout is only valid for October 2022 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly. Adenosine triphosphate (ATP) is used indirectly for which of the following processes? (A) Accumulation of Ca2+ by the sarcoplasmic reticulum (SR) (B) Transport of Na+ from intracellular to extracellular fluid (C) Transport of K+ from extracellular to intracellular fluid (D) Transport of H+ from parietal cells into the lumen of the stomach (E) Absorption of glucose by intestinal epithelial cells 1-28 Costanzo LS. BRS Physiology. 7th ed. 2019 Because all secondary active transports (e.g. SGLT-1), relies on the Na+- gradient created by the Na+-K+-ATPase pump. Dr. Banzuela A new drug is developed that blocks the transporter for H+ secretion in gastric parietal cells. Which of the following transport processes is being inhibited? (A) Simple diffusion (B) Facilitated diffusion © Topnotch Medical Board Prep (C) Primary active transport (D) Cotransport Mnemonic: SGLT-1 is in the small intestines, SGLT-2 is in the kidneys. Think (E) Countertransport 1-32 Costanzo LS. BRS Physiology. 7 ed. 2019 th of it this way: you have 1 Intestine, but you have 2 kidneys: SGLT-1 and SGLT-2. H+-K+-ATPase pump is the proper term for the proton pump of the Dr. Banzuela parietal cells of the stomach. It is a Primary Active Transport, Sodium-Calcium Countertransport (Na+-Ca2+ Exchange) countertransport. o Na+ moves downhill, Ca2+ moves uphill, they move in opposite Dr. Banzuela directions o Na+-Ca2+ exchange in the cardiac membrane: decreases 1.3 OSMOSIS intracellular Ca2+ OSMOLARITY o MOA of Digoxin: inhibits cardiac Na+-K+-ATPase Pump → Concentration of osmotically active particles in a solution inhibits Na+-Ca2+ pump → greater intracellular calcium → Measured in Osmoles/Liter GREATER CARDIAC CONTRACTILITY “Pogi” points of water § Hypokalemia increases the risk and severity of digitalis o The higher the osmolarity of a solution, the more it attracts toxicity because: hyperpolarized cardiac membrane → water from an opposite compartment further increased inhibition of the Na-K-ATPase pump 𝑂𝑠𝑚𝑜𝑙𝑎𝑟𝑖𝑡𝑦 = 𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 × # 𝑜𝑓 𝐷𝑖𝑠𝑠𝑜𝑐𝑖𝑎𝑏𝑙𝑒 𝑃𝑎𝑟𝑡𝑖𝑐𝑙𝑒𝑠 ✔ GUIDE QUESTIONS 𝑚𝑂𝑠𝑚/𝐿 = 𝑚𝑚𝑜𝑙/𝐿 × 𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓𝑝𝑎𝑟𝑡𝑖𝑐𝑙𝑒𝑠/𝑚𝑜𝑙 Which of the following characteristics is shared by simple and facilitated Normal ECF Osmolarity: 300 mOsm/L diffusion of glucose? Normal ICF Osmolarity: 300 mOsm/L (A) Occurs down an electrochemical gradient (B) Is saturable Normal values differ depending on the textbook that you are going to use (C) Requires metabolic energy – so do not obsess about it, at alam din yan ng examiners – they rarely ask (D) Is inhibited by the presence of galactose you what is the normal value of this or that. In some books, ECF and ICF (E) Requires a Na+ gradient 1-1 Costanzo LS. BRS Physiology. 7 ed. 2019. th osmolarity is 285, in other books it’s 310. The values here reflect commonly accepted normal values by physiology teachers in the Philippines. Movement is from high-concentration to low-concentration. Dr. Banzuela Dr. Banzuela *ECF and ICF are Isoosmotic relative to each other! Transport of D- and L-glucose proceeds at the same rate down an electrochemical gradient by which of the following processes? Substance with an osmolarity/osmolality of zero: Water (A) Simple diffusion Movement of water across a semipermeable membrane from a (B) Facilitated diffusion solution with low solute concentration to a solution with high (C) Primary active transport solute concentration (D) Cotransport Remember: water utilizes OSMOSIS and not simple diffusion. Water will (E) Countertransport 1-18 Costanzo LS. BRS Physiology. 7 ed. 2019. th move according to CONCENTRATION GRADIENT (concentration Glucose is supposed to be transported via carrier-mediated means. differences between two compartments) and not according to volume Dapat may stereospecificity, so normally hindi same rate and transport differences between two compartments. Water will move from LOW ng D-glucose at L-glucose. Pag same lang rate of transport ng D-glucose CONCENTRATION (“dilute” compartment) to HIGH-CONCENTRATION and L-glucose, ibig sabihin hindi siya carrier-mediated – simple (“concentrated” compartment). Do not confuse water movement (osmosis) diffusion na siya. Ingat, this is a tricky question since the transport of with solute movement using simple diffusion. D-glucose and L-glucose is not through simple diffusion in real life. Dr. Banzuela Dr. Banzuela Driving Force: Osmotic Pressure Which of the following would occur as a result of the inhibition of Na+,K+- o Osmotic Pressure computed using van’t Hoff’s Law ATPase? (A) Decreased intracellular Na+ concentration (B) Increased intracellular K+ concentration (C) Increased intracellular Ca2+ concentration (D) Increased Na+–glucose cotransport (E) Increased Na+–Ca2+ exchange 1-23 Costanzo LS. BRS Physiology. 7 th ed. 2019. If you inhibit the primary transport Na-K-ATPase pump, you will prevent Na+-gradient in the ECF from occurring. This would then prevent all secondary active transport processes including the Na+- Ca2+ pump (a pump that causes Na+ influx and Ca2+ efflux). Less calcium then goes out, leading to increased intracellular calcium concentration. A drug that inhibits Na+-K+-ATPase pump: think DIGOXIN. Dr. Banzuela Which of the following transport processes is involved if transport of glucose from the intestinal lumen into a small intestinal cell is inhibited by abolishing the usual Na+ gradient across the cell © Topnotch Medical Board Prep membrane? 𝝅 = 𝒈 × 𝑪 × 𝑹𝑻 (A) Simple diffusion where: (B) Facilitated diffusion π = Osmotic pressure (atm or mm Hg) (C) Primary active transport g = Number of particles per mole in solution (Osm/mol) (D) Cotransport C = Concentration (mmol/L) (E) Countertransport 1-25 Costanzo LS. BRS Physiology. 7 ed. 2019. th R = Gas constant (0.082 L − atm/mol − K) SGLT-1 is used to transport glucose from S.I. lumen to S.I. cells. It is a T = Absolute temperature (K) secondary active transport utilizing co-transport-symport. Walang Secondary active transport sa choices, so best answer is co-transport. Dr. Banzuela TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA Page 4 of 97 For inquiries visit www.topnotchboardprep.com.ph or email us at [email protected] This handout is only valid for October 2022 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.  TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA For inquiries visit www.topnotchboardprep.com.ph or https://www.facebook.com/topnotchmedicalboardprep/ This handout is only valid for October 2022 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly. EFFECTIVE OSMOTIC PRESSURE ✔ GUIDE QUESTIONS Effective Osmotic Pressure = Osmotic Pressure x Reflection In a hospital error, a 60-year-old woman is infused with large volumes of Coefficient a solution that causes lysis of her red blood cells (RBCs). The solution Same effective osmotic pressure: Isotonic was most likely: Higher effective osmotic pressure: Hypertonic (A) 150 mM NaCl Lower effective osmotic pressure: Hypotonic (B) 300 mM mannitol (C) 350 mM mannitol Rule: water undergoes osmosis from hypotonic solution to (D) 300 mM urea hypertonic solution (E) 150 mM CaCl2 1-9 Costanzo LS. BRS Physiology. 7 ed. 2019 th Osmotic pressure exerted by proteins: Oncotic Pressure or A and B are isotonic compared to the RBC ICF (yung A, kaya Colloid Osmotic Pressure 5hypoosmotic isotonic, remember na magseseparate yung Na and Cl, Remember that proteins can exert osmotic pressure, it can attract water. kaya and actual effective osmotic pressure nyan ay 150 x 2 = 300. C and This is the basis for ONCOTIC pressure – something that you will read again E are hypertonic (C is hypertonic dahil 150 x 3 naman). D is hypotonic and again in this handout. – not because of the concentration na 300, but because ang RC niya is Dr. Banzuela less than 1 (ineffective osmole siya, so ang effective osmotic pressure niya is actually less than 300). Because D is hypotonic, water will move from ECF to ICF causing cellular swelling, and eventually, cellular RBC AND OSMOSIS rupture. Dr. Banzuela https://qrs.ly/h9dpclw Solutions A and B are separated by a semi-permeable membrane. Solution A contains 1 mM sucrose and 1 mM urea. Solution B contains 1 mM sucrose. The reflection coefficient for sucrose is one and the Refer to this audio file as you look at the picture below. reflection coefficient for urea is zero. Which of the following Dr. Banzuela statements about these solutions is correct? (A) Solution A has a higher effective osmotic pressure than solution B (B) Solution A has a lower effective osmotic pressure than solution B (C) Solutions A and B are isosmotic (D) Solution A is hyperosmotic with respect to solution B, and the solutions are isotonic (E) Solution A is hypoosmotic with respect to solution B, and the solutions are isotonic 1-17 Costanzo LS. BRS Physiology. 7th ed. 2019 Iba ang osmotic pressure sa effective osmotic pressure (see these formulas in the previous discussion). Urea osmotic pressure is 1mM. Pero yung effective osmotic pressure niya is zero. So, solution A is hyperosmotic but same lang ang tonicity sa solution B (since ang terms © Topnotch Medical Board Prep na “isotonic”, “hypertonic” and “hypotonic” refer to effective osmotic REFLECTION COEFFICIENT (OSMOTIC COEFFICIENT) pressure and not just osmotic pressure) Dr. Banzuela Number between zero and one Assuming complete dissociation of all solutes, which of the following Describes ease by which solute permeates a membrane solutions would be hyperosmotic to 1 mM NaCl? RC DESCRIPTION EXAMPLE NOTES (A) 1 mM glucose Effective (B) 1.5 mM glucose No solute One Albumin Osmole (C) 1 mM CaCl2 penetration (D) 1 mM sucrose (creates Osm P) Between (E) 1 mM KCl From Physiology BRS, 6 Ed th Some solute Most 1mM x 3 kasi ang C. Zero and - penetration substances Dr. Banzuela One Ineffective Complete Osmole 1.4 DIFFUSION POTENTIAL, RESTING MEMBRANE Zero solute Urea POTENTIAL, ACTION POTENTIAL (No osmotic penetration effect) ION CHANNELS Cell membrane integral proteins that permit passage of certain ions o Selective for specific ions o Maybe open or closed Characteristics of ion channels selectivity based on distribution of charges and size of channels. Small channel lined with negatively charged groups will exclude large solutes for example Dr. Banzuela VOLTAGE-GATED LIGAND-GATED CHANNELS CHANNELS Opened or closed Opened or closed by by changes in Mechanism hormones, 2nd membrane messengers, NTs potential Skeletal Muscle AChR (NM Activation vs. Receptor) that opens gate Examples Inactivation gate of for Na+ and K+ when Ach nerve Na+ channel binds Don’t be afraid of the term “ligand”. Ligand means “messenger.” That messenger can either be hormones or neurotransmitters. Dr. Banzuela DIFFUSION POTENTIAL AND EQUILIBRIUM POTENTIAL REFLECTION COEFFICIENT (σ) © Topnotch Medical Board Prep Diffusion Potential Look at the pic above. Wag matakot sa RC. Think of RC as a formula: o Potential difference generated across a membrane because of RC = amount “returned”/amount “sent” a concentration difference of an ion Albumin has an RC of one – meaning if 8 molecules of Albumin try to Equilibrium Potential (Nernst Potential) penetrate the membrane, none will be able to do so. 8 “sent”, 8 “returned”. o Diffusion potential that exactly balances (opposes) the tendency RC = 8/8 = 1. Albumin has an RC of 1. It’s an effective osmole and attracts for diffusion caused by concentration difference water to where it is concentrated. Urea has an RC of 0. If 8 molecules of urea try to penetrate the membrane, o At electrochemical equilibrium, chemical and electrical driving 8 molecules (all molecules) will penetrate. RC = 0/8 = 0. Urea has RC of forces that act on an ion are equal and opposite; no net diffusion zero. It’s an ineffective osmole and cannot easily attract water. occurs Dr. Banzuela TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA Page 5 of 97 For inquiries visit www.topnotchboardprep.com.ph or email us at [email protected] This handout is only valid for October 2022 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.  TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA For inquiries visit www.topnotchboardprep.com.ph or https://www.facebook.com/topnotchmedicalboardprep/ This handout is only valid for October 2022 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly. o Calculated by Nernst Equation: In terms of action potential – remember the 3 characteristics – Stereotypical size and shape (meaning if I graph it, I will get the same thing again and again), propagation (kumakalat – pag nag AP ang isang cell, magkakaroon ng AP yung next cell) and all-or-none (“on” or “off” state. It will be in the “on” state once threshold is reached. Dr. Banzuela NERVE ACTION POTENTIAL Depolarization o Opening of Na-Activation Gate (m gate) → Na inward current Repolarization o Closure of Na-Inactivation Gate (h gate) → stop Na inward current o Equilibrium Potentials in Nerve and Muscle: o Opening of K gates → K outward current o ENa+ = +65mV, ECa2+ = +120mV, EK+ = -85mV, ECl- = -85mV Depolarization – net inward current, cell interior becomes less negative (you turn it “on”). Repolarization – you make the cell more negative (you turn it “off”). Look at the Na+-Channels and the K+-channels of an excitable cell like neurons above. The Na channels has two gates similar to an anteroom/waiting room. These two gates are the Na-activation and Na- inactivation gates. At rest, the Na-activation gates (m gate) is closed, while the Na-inactivation gates (h gate) is open. K-channels have just one gate. When you have depolarization, the Na-activation gates open. And since Na concentration is greater in the ECF compared to the ICF, Na influx will occur, causing the cell to become more positive. In repolarization, Na+-inactivation gates close (preventing Na+-influx) and K gates open (causing positive charges to leave the cell, making the cell more negative). Dr. Banzuela © Topnotch Medical Board Prep ✔GUIDE QUESTION Solutions A and B are separated by a semipermeable membrane that is permeable to K+, but not to Cl–. Solution A is 100 mM KCl, and solution B is 1 mM KCl. Which of the following statements about solution A and solution B is true? (A) K+ ions will diffuse from solution A to solution B until the [K+] of both solutions is 50.5 mM (B) K+ ions will diffuse from solution B to solution A until the [K+] of both solutions is 50.5 mM (C) KCl will diffuse from solution A to solution B until the [KCl] of both solutions is 50.5 mM (D) K+ will diffuse from solution A to solution B until a membrane potential develops with solution A negative with respect to solution B (E) K+ will diffuse from solution A to solution B until a membrane potential develops with solution A positive with respect to solution B 1-3 Costanzo LS. BRS Physiology. 7th ed. 2019 K+ is positively charged. It will move from Solution A to B (high concentration to low concentration). Solution A will now become negative compared to Solution B. Dr. Banzuela RESTING MEMBRANE POTENTIAL Exhibited by all cells By convention, refers to intracellular charge Established by diffusion potentials resulting from concentration differences of various ions as each attempt to drive the membrane potential towards its equilibrium potential Normal Nerve RMP: -70mV o Caused by: § Nernst Potential for Na+ and K+ § K+ Leak Channels § Na+-K+-ATPase Pump o Closer to EK+ −85mV ENa+ +65mV § Nerve membrane more permeable to K+ than Na+ (high resting conductance to K) Causes reduction of potassium leak out of the cells: Hyperpolarizing the membrane potential © Topnotch Medical Board Prep ACTION POTENTIAL Exhibited only by excitable cells (neurons, all muscle types) Consists of rapid depolarization/upstroke (“on”) followed by repolarization (“off”) Characteristics of a True Action Potential: 1. Stereotypical size and shape: each normal AP for a given cell type looks identical, depolarizes to the same potential and repolarizes to the same RMP 2. Propagating: AP at one cell causes depolarization of adjacent cells in a nondecremental manner 3. All-or-none: if threshold is reached, a full-sized AP will be produced, otherwise, none at all Remember: all cells have a Resting Membrane Potential. But only excitable cells have an Action Potential. These excitable cells are neurons, skeletal muscle, cardiac muscles, and smooth muscles. © Topnotch Medical Board Prep TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA Page 6 of 97 For inquiries visit www.topnotchboardprep.com.ph or email us at [email protected] This handout is only valid for October 2022 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.  TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA For inquiries visit www.topnotchboardprep.com.ph or https://www.facebook.com/topnotchmedicalboardprep/ This handout is only valid for October 2022 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly. SPECIAL NOTES: ACTION POTENTIAL Remember: the thicker the nerve, the faster it is. The more myelinated the TERM DESCRIPTION nerve, the faster it is. Myelin is an insulator, not a conductor, produced by Schwann Cells (in the peripheral nervous system or PNS) and Depolarization Make the MP more positive Oligodendrocytes (in the central nervous system or CNS). AP is Hyperpolarization Make the MP more negative REGENERATED in each Node of Ranvier – this ensures that no matter how Positive charges flow into the cell far you are from the initial segment/axon hillock (where AP is first Inward Current generated), the strength of the signal is maintained, since regenerated causing depolarization yung AP in each Node of Ranvier. Positive charges flow out of the cell Outward Current Dr. Banzuela causing hyperpolarization ✔GUIDE QUESTION MP where AP is inevitable The velocity of conduction of action potentials along a nerve will be o net inward current > net increased by __________. Threshold outward current (A) stimulating the Na+–K+ pump o Na+ inward current > K+ outward (B) inhibiting the Na+–K+ pump current from K leak channels (C) decreasing the diameter of the nerve Occurs during an AP when (D) myelinating the nerve Overshoot (E) lengthening the nerve fiber MP > 0mV 1-16 Costanzo LS. BRS Physiology. 7 ed. 2019 th Undershoot Occurs during an AP when (After-hyperpolarization) MP < RMP 1.5 NEUROMUSCULAR AND SYNAPTIC Occurs during an AP when no new TRANSMISSION Absolute Refractory AP can be elicited no matter how SUPPORTING CELLS OF THE NERVOUS SYSTEM Period (ARP) large the stimulus (NON-NEURONS) Basis: closed Na+-inactivation gates CHARACTERISTICS CELL Occurs during an AP after ARP when A tissue macrophage that act as a new AP can be elicited by required scavenger cells, removing debris Relative Refractory greater than usual Na+ inward resulting from injury, infection, and Period (RRP) current MICROGLIA disease (e.g., multiple sclerosis, Basis: prolonged opening of K+ AIDS-related dementia, Parkinson channels disease, & Alzheimer disease) Occurs when cell membrane is Macroglia that forms myelin in the OLIGODENDROCYTES depolarized but not rapidly enough, CNS and PNS respectively & SCHWANN CELLS Accommodation thus causing Na-inactivation gates Helps in regeneration and SCHWANN CELLS to eventually close → no AP remyelination in the PNS e.g. Hyperkalemia Macroglia that send processes that non-propagated local potential envelop synapses and the surface of ASTROCYTES Electrotonic potential due to local change in ionic nerve cells, and helps form the BBB conductance Astrocytes in the white matter FIBROUS ASTROCYTES local electrical charge in the Astrocytes in gray matter, with Generator potential / generator/sensitive region of the granular cytoplasm and produce Synaptic Potential receptor cell substances that are tropic to PROTOPLASMIC graded potential neurons to help maintain ASTROCYTES principal inputs signals to which a appropriate concentration of ions neuron responds and NTs by taking up K+ and the NTs Synaptic potentials Glutamate and GABA conductance changes are triggered by neurotransmitters PARTS OF THE NEURON ✔GUIDE QUESTIONS During the upstroke of the nerve action potential (A) there is net outward current and the cell interior becomes more negative (B) there is net outward current and the cell interior becomes less negative (C) there is net inward current and the cell interior becomes more negative (D) there is net inward current and the cell interior becomes less negative 1-2 Costanzo LS. BRS Physiology. 7 ed. 2019 th A newly developed local anesthetic blocks Na+ channels in nerves. Which of the following effects on the action potential would it be expected to produce? (A) Decrease the rate of rise of the upstroke of the action potential (B) Shorten the absolute refractory period (C) Abolish the hyperpolarizing afterpotential (D) Increase the Na+ equilibrium potential PARTS OF A (E) Decrease the Na+ equilibrium potential 1-20 Costanzo LS. BRS Physiology. 7th ed. 2019 NEURON https://qrs.ly/2bdpcm7 Lidocaine blocks neuronal voltage-gated sodium channels responsible for action potential generation and propagation. It can also act on cardiac Refer to this audio file as muscles and cause arrhythmias. you look at this picture. Dr. Banzuela Dr. Banzuela PROPAGATION OF ACTION POTENTIAL Done through local currents to adjacent areas of the membrane Conduction velocity is increased by: o Fiber Size: the larger the nerve fiber, the smaller the internal resistance, and the faster the conduction velocity o Conduction velocity is most dependent on: nerve diameter o Myelination: myelin acts as insulator. AP is regenerated in Nodes of Ranvier (unmyelinated portions of the axon) that contains the highest concentration of Na+ channels per square micrometer of cell membrane © Topnotch Medical Board Prep Conduction Velocity = Distance/Latent Period Dendrites: where NT receptors are found Cell Body (Soma): where organelles, nucleus is seen TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA Page 7 of 97 For inquiries visit www.topnotchboardprep.com.ph or email us at [email protected] This handout is only valid for October 2022 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.  TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA For inquiries visit www.topnotchboardprep.com.ph or https://www.facebook.com/topnotchmedicalboardprep/ This handout is only valid for October 2022 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly. Speaking of nucleus – the nucleus of the cell is the one that controls and SYNAPTIC TRANSMISSION regulates cellular activities since it is the one that carries the genes that is PHENOMENON CAUSED BY used in the production of cellular proteins like enzymes. Endplate Potential Dr. Banzuela Increase in Na+ Conductance (Na+ Initial Segment: where AP starts (in skeletal muscle motor endplate) Influx) Axon: transmitting portion Can be caused by opening of Cl- Nodes of Ranvier: unmyelinated portion of the axon Fast Inhibitory Post- Channels (Cl- Influx), opening of K+ Neural Fibril: branches of the axon Synaptic Potential channels (K+ efflux), or closure of (IPSP) Na+ or Ca2+ channels Fast Excitatory Post- Increase in Na+ Conductance (Na+ Synaptic Potential (Fast Influx) or Ca2+ Conductance (Ca2+ EPSP) influx) Slow Excitatory Post- Decrease in K+ Conductance (Slow K+ Synaptic Potential efflux) (Slow EPSP) Opening of voltage-gated K+ channels Presynaptic Inhibition (K+ Efflux) Adapted from 6-1, 6-7, 6-8. Barrett et al. Ganong’s Review of Medical Physiology. 26th ed. 2019 ✔GUIDE QUESTION An inhibitory postsynaptic potential: (A) depolarizes the postsynaptic membrane by opening Na+ channels (B) depolarizes the postsynaptic membrane by opening K+ channels (C) hyperpolarizes the postsynaptic membrane by opening Ca2+ channels (D) hyperpolarizes the postsynaptic membrane by opening Cl- channels 1-22 Costanzo LS. BRS Physiology. 7 ed. 2019 th © Topnotch Medical Board Prep Remember – you can inhibit an AP several ways – cause Cl- influx, or Terminal Boutons (End-Feet): distal tips of the axon cause K+ efflux or inhibit Na+ influx/Ca2+ influx. All of these will make the cell more negative/less positive. Voltage-Gated Calcium Channels (VGCC): stimulated by AP; Dr. Banzuela triggers release of NT into the synapse NEUROTRANSMITTERS (NTS) o LAMBERT-EATON MYASTHENIC SYNDROME: autoimmune disease marked by auto-antibodies against these voltage-gated Function of NTs: Chemical messengers calcium channels → prevents Acetylcholine from being released For communication between neurons to the neuromuscular junction Maybe excitatory or inhibitory or both Synapse: space between neurons Categories: NTs: either excitatory (depolarizes) or inhibitory o Small-Molecule NTs (hyperpolarizes); binds to post-synaptic receptors § Monoamines: e.g. Ach, Serotonin, Histamine § Catecholamines: Dopamine, NE, Epi CLINICAL CORRELATES MULTIPLE SCLEROSIS § Amino Acids: Glutamate, GABA, Glycine o Large-Molecule NTs Multiple Sclerosis: autoimmune disease directed against the § Neuropeptides including substance P, enkephalin, components of the myelin sheath vasopressin, and a host of others o Brain MRI and CSF analysis (presence of oligoclonal bands): used to diagnose MS NEUROTRANSMITTERS Associated with HLA-DR2