Lecture 1 (1/24) (Collins)

Lecture 1 (1/24) (Collins) Physiology The study of how cells interact with their environment to obtain the things requires for life (water, salts, heat, etc.) Exchange systems Systems that allow for the exchange of material. o For ex. respiratory system, circulatory system, etc. 4 levels of organization Cellular, Tissue, Organ, and System. There are 5 Basic Principles o All Life is Aquatic. Water is 75% of body weight, 99% of all molecules. o All life is compartmentalized Basic unit is the cell ICF = Intercellular fluid aka cytoplasm ECF = extra cellular fluid. There are 2 types: Interstitial fluid ECF between cells Plasma Blood Asymmetries between Compartments help maintain a potential difference. This I needed for physiological functions. For ex. More Na+ in ICF, and little in ECF. o All Life deals with the same fundamental problems. All Life requires an input of energy ATP is principal form of energy. This is done through either aerobic (w/ oxygen) or anaerobic (without oxygen) cellular respiration. Metabolism Sum of all energy-requiring life processes. Metabolic Rate (MR) - metabolism in a unit of time. Basal Metabolic Rate Lowest possible (resting) MR. o All Life is constrained by the laws of physics and chemistry. Size principle relationship between surface Area (SA) & Volume. As animal gets bigger, the SA/V ratio gets smaller. This means that relative SA for exchange goes down. Large animals exchange substances worse, but retain better. Small animals exchange well, but retain worse. o All life can only tolerate a limited range of living conditions. Ex. H20 level, salts, nutrients, etc. Homeostasis: maintenance of a relatively constant internal environment. Requires negative feedback Feedback-

A feedback mechanism has 3 components o Sensor checks the level o Integrator compares sensor level to set point and takes an action o Effector device used to fix the level back to set point. Negative feedback if things vary from set point you act to fix things back to set point o Ex. Thermostat. Positive feedback Positive things lead to more. o Leads to rapid changes. o Ex. when you get money, you want more... you don t want to return to the previous condition. o Ex. Waves of contraction during labor stimulate even more waves of contraction. Lecture 2 (1/26) (Collins) A food-energy budget must be maintained. o Energy in (food) = energy out (work, synthesis,heat) Nitrogenous wastes (ammonia) have to eliminate from the body. There are 3 ways to do this: o Ammonotelic get rid of pure ammonia. Lots of water is needed, but no energy is required. This is used by fish. o Ureotelic Ammonia is converted to urea at the cost of ATP. This makes it less toxic and less water is needed. Mammals use this. o Uricotelic Ammonia is converted to uric acid requires almost no water to get rid of, but lots of ATP. This is used by birds i.e. bird shit. Heat can be obtained via 2 methods o Environment animals get heat from the environment o Endogenous Heat is produced by the animal for itself. There are 4 ways to transfer heat: o Conduction By touching things. Temperature gradient (T2-T1) is driving force. Rest is controlled by a constant- Surface area & length between objects. Thermal conductivity (metals have most, air least) o Convection By air. There are 2 ways. Free convection air doesn t move; natural heat rises. 1

Boundary layers form around you, with layers of heat gradually going from body heat to ambient. Forced convection disrupts the boundary layers. Ex. fan. o Evaporation Liquids absorb heat from skin and become vapor, thereby cooling the animal. Ex. Sweating, panting. o Radiation just letting off heat through skin. Absorbing heat due to environment/sunlight. Counter current heat exchange - When you 2 fluids flowing in different directions (ex. Veins and arteries that touch), very efficient heat exchange will occur. o This is used by mammals and birds to prevent heat loss in the extremities. Lecture 3 (1/31) (Collins) Body temperature (Tb) must be regulated so that enzymes function and don t denature. 2 Main strategies for maintaining body temp: o Ectotherms Use external heat to thermoregulate All non-vertebrates, amphibians, reptiles, fishes. Body temperature is dependent on Tambient. No insulation. Low MR. Limited physiological change (ex. vasoconstriction. Behavioral thermoregulation. o Endotherms Generate own heat (endogenous) via MR. Energetically very costly. Used by mammals and birds. Lots of insulation (fur, etc.). High MR. Physiological change. Behavioral thermoregulation in addition to endogenous.) MR varies with Tamb in Ectotherms. o At low Tamb, MR is lower, so animal uses less energy and is slow. o At High Tamb, MR is higher; animal uses more energy and is fast. MR varies differently with Tamb in endotherms. o As Tamb gets lower, MR increases to maintain body temp (Shivers) o At a certain range, you have the thermoneutral zone (TZ). At this zone, thermoregulation can happen without MR. Animal s MR is at the basal metabolic (Resting) rate. o After you pass the TZ, you use MR to lower body temp (sweating) Behavioral Thermoregulation animals use behavior to thermoregulate. o E.g. stay in the sun in the day, go underground in the night. o Heliotherm use the sun as the heat source o Thigmotherm use substrate (earth, rocks, etc.) to get heat. Thermal acclimation: slow transition from one environment to another o Done by selective synthesis of different forms of same enzyme 2

o Isoenzymes isoforms of enzymes. Only one can be produced at a time. They have different optimal temps and MR s. Heterotherms- Animals capable of varying degrees of heat production. o Temporal Heterotherms - Tb (hibernation, day/night fluctuations) Hibernation regulate Tb, but at much lower level). Torpor (birds, small mammals suspend thermoregulation and let Tb get very low. o Regional Heterotherms different temps at a different parts Ex. Testes in mammals. Thermogenesis Converting chemical energy into heat o Shivering thermogenesis muscle contractions make heat o Non-shivering thermogenesis metabolizing fat to make heat Brown adipose tissue (BAT) is a specialized fat for this. It s found in neck/shoulders in mammals. It heats up quickly and is highly vascularized. Temperature is regulated using 3 components. (negative feedback) o Sensor measures level. In humans, this is in preoptic area/anterior hypothalamus o Integrator compares level to set point and controls effector. Set point the temperature it s supposed to be at. In humans, this is in the same area as the sensor. o Effector Regulates everything so it returns to the set point. In humans, effectors are shivering, BAT, etc. Pyrogens are fever producing substances o Exogenous pyrogens are very potent and produced by gram negative bacteria. o Endogenous pyrogens are produced by the body itself (like from White blood cells) They can also be released due to exogenous pyrogens. Lecture 4 (2/2) (Collins) Fluid and ion concentrations must be balanced and kept constant Body fluids are compartmentalized ICF, Interstitial fluids, Plasma. Solvent the liquid that things dissolve in (ex. H20) Solute the things that dissolve in solvent salts, ions, etc. Diffusion the movement of things from high conc. to low conc. o Osmosis Diffusion of fluids/water. o Passive no energy is needed. o Driven by the concentration differential (C2-C1). The cell membrane is selective permeable and highly regulated. o Hydrophobic substances can easily diffuse through o Hydrophilic substances cannot pass through directly. 3

o Lipophobic- molecules that can t go through the membrane o Lipophilic molecules that can diffuse through the membrane. Cells regulate lipophoic things through aqueous pores (ion channels) o Aquaporins special channels for water o Can open and close as needed. o Each channel is selective to its own specific ions. Water balance must be maintained. o There is no active transport of water only osmosis. The concentrations of solutes cause osmosis o Water moves from areas of less solute (high conc. of water) to areas of high solute (low conc. of water) Osmotic pressure the pressure produced by osmosis 1 osmolars (Osm) 1 mole/1 liter. o Molecules can dissociate though. For ex. NaCl will become NA+ and CL-.. So 1M of NaCl will become 2 osmolars o Remember as the # of osmolars goes up, it means that the amount of solute rises. Solute Osmolars Concentration of water o Therefore, water flows from low osmolars to high osmolars! Terms uses to describe osmolarity describe the amount of solute o osmotic : used for compartments and non-bio things Needs a frame of reference! Be careful! o tonic: used for cells. Frame of reference is always the cell! o Hypo less concentration. Iso same conc. Hyper high concentration. Ex. compartment A is hypoosmtic to compartment B. o This means compartment A has less solute compared to B. o This means compartment A has a lower osmolars than B. o This means water will flow from A to B. Lecture 5 (2/7) (Collins) Osmoregulator regulate the osmolarity inside the body Osmoconformer live isosmotic to the environment. They conform to the environmental conditions Euryhaline animal that survive over a wide range of conditions Stenohaline animal that can only tolerate a limited range. Ionoconformer uses the same ion concentrations from the environment Ionoregulator regulates the ion concentrations. Vertebrates are osmoregulates with a Body fluid osmotic concentration (BFOC) of ~300 mosm. They have to maintain water budgets! o Ions balance and water concentrations are linked! Osmolarity is a function of ion concentration over volume of water 4

Factors to consider in terms of H2O/ion balance: o Availability of H20 and salts. Aquatic vs. terrestrial, etc. o Respiration (passive water loss) and temp for terrestrials. o Skin (integument) permeability it varies between animals Frogs/amphibians : very permeable Reptiles/desert creatures/birds/mammals: very impermeable Sweating by humans is an exception. Still impermeable. o Food intake of water and salts. o Excretion how much is gotten rid of. Skin, salt glands, etc. There s a lot of difference between fresh water and salt water fish o Fresh water has 1 mosm while fish try to maintain 300 mosm Fish gain water and ions from gills, excrete through kidney o Salt water has 1000 mosm while fish try to maintain 300 mosm Fish drink lots of water and ions. They lose lots of water and ions through gills. o Smoltification remodeling the pumping process in salmon as they change from freshwater to seawater. It s meditated by hormones, and the number and size of chloride cells that pump out Cl- out of the gills. Transport epithelia cells are very important! o Apical membrane outward facing membrane (external envir.) o Basal membrane facing towards inward towards the tissue o There are transporters on both membranes for through transport. Epithelial cells are connected by tight junctions o This means that they form an impermeable sheet of cells. o Transcellular transport transport through the cell. o Paracellular transport transport between cells (not through) They are used to pump ions and other substances through the body. o For ex. glucose from the intestines to the blood stream. o They have lots of mitochondria to provide the energy needed o These help to maintain balance of substances and ions. Lecture 6 (2/9) (Cabot) The distribution of electrolytes (ions) in fluid compartments (ECF, ICF, ISS) is main focus. o The compartments are all in osmotic equilibrium. The only exception is that the plasma has more proteins then the rest. o However, all compartments are in chemical disequilibrium. o Also, the compartments are in electrical disequilibrium. Plasma compartment o Electrolytes (Na, K, Cl, etc.) o Non electrolytes (glucose, etc.) 5

o Colloids- large negatively charged proteins. Major Cations (positive ions): Na+, K+, Ca2+. o In Plasma Na+ high o In ICF- K+ high. Ca2+ very low. Major Anions (negative ions): Cl-, bicarbonate Hco3-, Phosphate ions. o In plasma: Cl- and bicarbonate. o In ICF: phosphate Balance of charge the number of charges has to be identical (11+, 11- ) but the actual number of ions doesn t have to be equal. Electrical disequilibrium o Potential difference of about -70mv on the cell membrane This is the resting membrane potential This is the difference in potential between the ICF and ECF Negative inside cell, positive outside. Membrane potential has many causes o Separation of the electrolytes between compartments is one. Permeability of membrane drives the electrolytic imbalance. Not really the actual change in conc. Of ions!!! More channels, more permeability. o Potential can pull ions in as well. called the electrical force This will lead to the electro-chemical gradient. Equilibrium potential is the voltage generated in the membrane for a single ion that the membrane is permeable to. Equilibrium potential can be calculated using the Nernst equation. o Nernst potential = equilibrium potential. (units are millivolts) o It only applies to one ion at a time! o 61 is a gas constant and all E ion = ( 61 ) (log z 10 ( [ion] in o Z = valence electrons. so for ex. +1 for K+; -1 for Cl-; +2 for Ca2+ [ion] out )) Goldman-Hodgkin-Katz equation o Predicts the resting membrane potential for several permeable ions o 61 is a gas constant and all V m = 61 log ( P k[k + ] out +P Na [Na + ] out ) P k [K + ] in +P Na [Na + ] in o P is the permeability of the specific ion Permeability are relative o K really dominates the equation... Pk is almost 40x Pna o If you are adding other ions to the equation, remember that for negative ions the concentrations must be flipped (in/out) Conceptualizing the Goldman equation: 6

o THINK PERMEABILITY, NOT ION CONCENTRATION Assume that all concentrations are the same. Only permeability changes. o When things are logged, log (1) = 0. All logs over 1 get more positive as you increase value. All logs under 1 get smaller when you decrease value o What this means is that as the numerator of the fraction increases, the voltage increases. o When the denominator decreases, the voltage increases. o Ex. K is more on the inside than out. So it looks like (5/150) When you increase the permeability, the denominator will increase more than the numerator. This means voltage decrease. Carrier proteins move ions and substances across the membrane. o There are 3 types: Uniport only transports 1 molecule in one direction Antiport pumps 2 things in different directions. Symport secondary transport move 2 molecules in 1 way. o They are never open to both the ECF and ICF at the same time o Some use ATP, others are facilitated diffusion. o Some pumps are electrogenic pumps they help maintain the electrochemical gradient in the membrane. o Ex. Na/K pump pumps out Na, and pumps in K. Channel proteins form either open channels or gated channel o They form a pore continuity between ECF and ICF. o Open channels don t open/close. They stay open. Ex. aquaporins. o Gated channels are very important. 3 types: Mechanically gated channels Voltage gated channels (Gated by Na, K, Ca, etc.) Chemically gated channels (ligand gated channel) CFTR (cystic fibrosis transmembrane regulator) o A chemically/ligand gated channel. It s a Cl- channel. o cystic fibrosis is a disease when CFTR isn t able to be inserted Disease caused by mucous becoming thick and sticky o CFTR is regulated by the level of ATP inside the cell. o In normal conditions cl- and na+ flow in, H20 can t go through membrane, so the conc. of water outside increases dilutes sweat. o If Cl- can t go into cell (disease) the sweat is really salty. o In resp. tract, Cl- leaves cell and brings water with it... This makes a saline layer that forms under the mucous. Without saline layer, Mucous will clog up the bronchi and kill you. 7