BMS 100 Physiology Concepts II PDF

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 [ "𝑃𝑟𝑒𝑠𝑠𝑢𝑟𝑒 𝐹𝑜𝑟𝑐𝑒𝑠" − "𝐷𝑖𝑓𝑓𝑢𝑠𝑖𝑜𝑛 𝐹𝑜𝑟𝑐𝑒𝑠" ] 𝐹𝑙𝑢𝑥 = "𝑅𝑒𝑠𝑖𝑠𝑡𝑎𝑛𝑐𝑒 𝑡𝑜 𝐻2𝑂 𝑓𝑙𝑢𝑥" Starling forces - simplified 𝐅𝐥𝐮𝐱 = 𝐋𝐩 𝐏𝐜𝐚𝐩 − 𝐏𝐈𝐒𝐅 − 𝛔 𝛑𝐜𝐚𝐩 − 𝛑𝐈𝐒𝐅 Starling forces - simplified Variables: • 𝐋𝐩 = the “leakiness” of the capillary wall to water ▪ The “inverse” of resistance • • • • • 𝐏 = hydrostatic pressure 𝛑 = osmotic pressure “cap” = the fluid within the capillary “ISF” = the fluid within the interstitial space 𝛔 = how much protein leaks through the capillary wall 𝐅𝐥𝐮𝐱 = 𝐋𝐩 𝐏𝐜𝐚𝐩 − 𝐏𝐈𝐒𝐅 − 𝛔 𝛑𝐜𝐚𝐩 − 𝛑𝐈𝐒𝐅 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… ▪ It gives the energy gradient Nernst potential (−60𝑚𝑉) 𝑃 𝐸𝑃 = 𝑙𝑜𝑔10 𝑍𝑝 𝑃 𝑖 𝑜 • 𝐸𝑃 = the membrane voltage at which a particle (P) moves into and out of the cell at the same rate ▪ → Equilibrium • 𝑍𝑝 = the charge and valence of P (anions are negative) • 𝑃𝑖 𝑃𝑜 = 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 𝐸𝑃 = 𝑙𝑜𝑔10 𝑍𝑝 𝑃 𝑖 𝑜 Nernst potential (−61𝑚𝑉) 𝑃 𝐸𝑃 = 𝑙𝑜𝑔10 𝑍𝑝 𝑃 𝑖 𝑜 10 Na+ 1 K+ 9 anion- Net 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? • Why is there an unequal distribution of charge? 10 Na+ 1 K+ 9 anion- Net charge +2 8 K+ 1 Na+ 11 anionNet charge -2 Nernst potential (−61𝑚𝑉) 𝑃 𝐸𝑃 = 𝑙𝑜𝑔10 𝑍𝑝 𝑃 𝑖 𝑜 12 Na+ 1 K+ 13 anionNet charge 0 Na+ - 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+? Challenge • Hints: ▪ Goldman Field equation predicts the membrane potential when it is permeable to more than one substance V𝑚 = −61 × 𝑝𝐾 𝐾+ 𝑖+𝑝𝑁𝑎+ 𝑁𝑎+ 𝑖+𝑝𝐶𝑙 𝐶𝑙− 𝑜 𝑙𝑜𝑔10 𝑝𝐾 𝐾+ 𝑜+𝑝𝑁𝑎+ 𝑁𝑎+ 𝑜+𝑝𝐶𝑙 𝐶𝑙− 𝑖 • Basically the Nernst equation, but it relates the membrane potential to the relative permeability of the membrane to sodium, potassium, and chloride • 𝑝𝐾 = membrane permeability to K+, 𝑝𝑁𝑎 = 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 | No vascular disease 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 part-way 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?