BMS100_PHL1-21v1_F2022.pptx

Physiology Concepts II Flow Down Gradients – In-Class BMS 100 Week 4 Questions from prelearning? • Poiseuille’s law • Fick’s law • Ohm’s law Combining forces • There are many situations in physiology where more than one force acts on the same substance  Filtration through a capillary  diffu...

Physiology Concepts II Flow Down Gradients – In-Class BMS 100 Week 4 Questions from prelearning? • Poiseuille’s law • Fick’s law • Ohm’s law Combining forces • There are many situations in physiology where more than one force acts on the same substance  Filtration through a capillary  diffusion and hydrostatic pressure  Distribution of ions across a membrane  diffusion and electrostatic forces • Often these forces “pull” or “push” the same substance in opposite directions  Which way will the substance move? Starling forces The purpose of a capillary is to transport substances to and from tissues • Water   Hydrostatic pressure  Diffusion • “Everything else”  Diffusion  Protein-mediated transport  Endocytosis Starling forces - simplified Starling forces - simplified Starling forces - simplified Variables: • = the “leakiness” of the capillary wall to water  The “inverse” of resistance • • • • • = hydrostatic pressure = osmotic pressure “cap” = the fluid within the capillary “ISF” = the fluid within the interstitial space = how much protein leaks through the capillary wall Starling forces • These forces are difficult to measure experimentally  The value of the variables in different situations and in different locations is the subject of much debate • Flux vs. Flow?  Flux = flow along a defined membrane surface area • Describes tissue swelling in a wide variety of situations  Inflammation/infection  Changes in pressure within the circulation Starling forces and the microcirculation Nernst potential • We know that:  Charged particles can move across a membrane based on electrostatic forces • Energy “powering” movement along the gradient? Resistance?  Dissolved particles can move across a membrane based on their concentration gradient • Energy “powering” movement along the gradient? Resistance? • The Nernst equation tells us the balance…  Does the particle move into or out of the cell, assuming it can cross the membrane? Nernst potential • The equation for the Nernst potential accounts for the following:  Diffusional forces and electrical fields are very small at large distances • Distribution of ions very close to either side of the membrane  The charge of the particle  The ratio of the particles’s concentration intracellular:extracellular • It does not include the flow of ions (current) or the resistance of the membrane to flow… Nernst potential • = the membrane voltage at which a particle (P) moves into and out of the cell at the same rate   Equilibrium • = the charge and valence of P (anions are negative) • = ratio of intracellular:extracellular concentrations of P Describes the voltage across a membrane that is permeable to P given the ratio of [P] inside:outside Nernst potential (−60𝑚𝑉 ) [ 𝑃 ]𝑖 𝐸 𝑃= 𝑙𝑜𝑔10 𝑍𝑝 [𝑃]𝑜 Nernst potential 10 Na+ 1 K+ 9 anionNet charge +2 8 K+ 1 Na+ 11 anionNet charge 2 Nernst potential • Why is there an unequal distribution of sodium and potassium across the membrane?  ATPase • Why is there an unequal distribution of charge?  maintain negative resting membrane potential (more –ve inside cell) 10 Na+ 1 K+ 9 anionNet charge +2 8 K+ 1 Na+ 11 anionNet charge 2 Nernst potential 12 Na+ 1 K+ 13 anionNet charge 0 N a+ - 12 K+ 1 Na+ 13 anionNet charge 0 Nernst potential Why is it helpful to understand Nernst potentials? • Living cells always have a membrane potential  Established by selective transporters and channels • This charge and ion balance serves important functions:  Cellular signaling  Transport of substances  Regulation of cell volume • Medications and pathologies impact the membrane potential of many different types of cells Challenge • A neuron relies on an inside-negative membrane potential for the purposes of signaling  Action potentials  Graded potentials • The membrane potential is about -75 mV in many neurons  However, the Nernst potential for potassium is close to -90 mV  Why is the membrane potential of a neuron close to, but not the same, as the equilibrium (Nernst) potential for K+? • We have other ions Challenge • Hints:  Goldman Field equation predicts the membrane potential when it is permeable to more than one substance V • Basically the Nernst equation, but it relates the membrane potential to the relative permeability of the membrane to sodium, potassium, and chloride • = membrane permeability to K+, = membrane permeability to Na+… Physiology Concepts II Flow Down Gradients - Cases BMS 100 Week 4 Case 1 • Mary is a 64-year-old woman with a 17-year history of Type 2 diabetes mellitus controlled by metformin and diet. Today she presents with slowly progressive numbness and coldness in her feet. The right foot is worse than the left • On investigation, you note:  Mary’s right foot is cooler and more pale than her left foot  Her posterior tibial pulse is weaker on her right than on her left, and the dorsalis pedis pulse on her right is not detectable  The capillary refill time on the right great toe is 15 seconds, and on the left it is 3 seconds  She cannot disintguish between sharp and dull stimuli over her right foot Case 1 • Below are an arteriole and an elastic artery from a patient without vascular disease and one with type II diabetes Long-term DM disease | No vascular Small vessels (arterioles) Large vessels (elastic arteries) Case 1 – Questions to answer • Clearly correlate Mary’s findings on history and physical exam to the known vascular changes that accompany diabetes mellitus  Use the physico-chemical laws that were discussed in the pre-learning and the lecture • How many of these laws are in play? How many are less important?  Try to explain every clinical feature • are there some clinical features that are less likely to be due to vascular changes? What would these be? Case 2 • Robert is a 75-year-old gentleman with a long history of coronary artery disease and high blood pressure. He had been diagnosed with NYHA stage II heart failure 5 years ago. • Today he presents because:  his foot swelling has been getting worse – at the end of the day he has a great deal of difficulty putting on his shoes  He has become more short of breath in the last few days • On investigation you note:  His blood pressure is 156/98 mm Hg – other vitals are within normal limits  His feet are notably swollen, and this swelling continues partway up the shin  He is breathing quickly at rest – his respiratory rate is 25 breaths/min Heart failure – some basics Most patients with heart failure develop two general types of problems: • Impaired “forward-flow”  due to decreased cardiac output and worsening blood supply to important tissues like the brain, heart, kidneys  The tissues with poor blood supply suffer impaired function • “fluid backup”  Blood is not moved from the veins at its usual rate, since the ventricles have a worsened cardiac output  Blood “backs up” in the venous system Case 2 – Questions to answer • What aspect(s) of Robert’s medical history best explain his foot swelling? How about his shortness of breath? • How does these relate to the physicochemical laws discussed in the pre-learning and during the lecture?