1. Wiggers diagram summarizes the electrical, mechanical and anatomical events of a cardiac cycle. Describe electrical and pressure/volume changes during a cardiac cycle on the basis of the diagram.

2. Describe the changes in pressure and flow (volume) during a single beat of the mammalian heart (pressure-volume loop).

3. Discuss the factors that influence stroke volume of the heart. 4. Describe factors determining ventricular preload.

5. What are inotropes? How are they working to regulate cardiac performance? Describe how iontropes are different from chronotropes.

6. Overall goal of the CV system is to maintain MAP (mean arterial pressure). Describe 5 major factors which are involved in regulation of MAP by changing cardiac output and/or total peripheral resistance.

7. What are the percentages of oxygen, nitrogen, and carbon dioxide in dry air?

8. Under what conditions might you expect the fractional composition of air to vary? Total pressure? Understand how to calculate partial pressures in completely dry air (no water vapor pressure) as well as air with humidity at different temperatures. How does the O2 amount of air vary with altitude?

9. How does the solubility of oxygen in water compare with the solubility of carbon dioxide in water? Explain why carbon dioxide will dissolve more rapidly than oxygen to water, if both are at the same partial pressure.

10. How does temperature affect the solubility of gases in water? Ionic strength (i.e., fresh vs sea water)? How does the solubility of CO2 compare with that of O2 in water?

11. What are some of the important differences between air and water that affect the design of respiratory organs? ([O2], viscosity, diffusion rates).

12. Understand how a fish gill is arranged (i.e., gill arches, lamellae, the direction of water flow compared to blood flow)

13. Under what conditions would a fish use buccal pumping to ventilate its gills? Ram ventilation? Why is ram ventilation more energy efficient?

14. Understand the changes in the different lung volumes that occur as a person begins to exercise from a resting state (tidal volume increases, inspiratory and expiratory reserves decrease).

15. Know the difference between frequency of breathing and alveolar ventilation volume. Which improves alveolar ventilation rate more, increasing tidal volume or breath frequency?

16. Explain how hypoventilation results in hypercapnia (understand shifts in the reaction between CO2, bicarbonate and protons).

17. How is ventilation rate regulated in air breathers? (carotid and aortic body chemoreceptors, cerebrospinal chemoreceptors, pulmonary stretch receptors). What does the phrenic nerve do? Why does it make sense for the discharge activity of the phrenic nerve to be enhanced by high alveolar PCO2? What part of the brain coordinates inspiratory and expiratory neuron activity?

18. What are 3 important functions of respiratory pigments? Can you name two respiratory pigments other than hemoglobin?

19. A higher P50 indicates a greater or lower binding affinity between pigment and oxygen? How is O2 binding affinity affected by pH, organic phosphates (like DPG or inositol triphosphate), CO bound to Hb (carboxyHb)? Organisms at high altitude often (increase or decrease) DPG production? How does this improve gas transport to and from tissues?

20. Most of the CO2 in blood plasma is in what form (molecular CO2, bicarbonate or carbaminoHb)? Does the binding of oxygen affect the CO2 content of blood plasma (Haldane effect)?

21. Be able to explain how CO2 is converted to/from bicarbonate, how this affects the pH in the red blood cells, what is the role of carbonic anhydrase? (how do tissue vs lung capillaries differ in CA distribution?), what is the chloride shift?

22. Understand the role of the Bohr and Haldane effects (movement of O2 and CO2 in and out of plasma), both in lung and tissue capillaries. How does the pH inside a red blood cell compare when it is in a lung versus tissue capillary?

23. Compare and contrast the average volume and electrolyte composition of the three major fluid compartments (ICF and the two ECF compartments, plasma and interstitial fluid). What are some of the major non-electrolytes that contribute to fluid osmolarity?

24. What are the most important factors that affect how much water/ions are exchanged with the environment (you could list 5 altogether). Animals with a small surface to volume ratio tend to desiccate faster or slower? Define metabolic water. What produces more metabolic water, catabolism of a gram of fat or a gram of carbohydrate?

25. Compare the ionic composition of fresh versus sea water. How do you expect body fluids of an osmoconformer to behave along an osmolarity gradient? An osmoregulator? Give an example (groups of taxa) of each.

26. What compounds do some organisms (sharks and rays, other elasmobranchs) use to maintain high osmolarity of body fluids?

27. Marine teleosts tend to (lose/gain) water to their environment. As a result, they have mechanisms to actively (secrete/absorb) ions at the gill interface.

28. How marine reptiles and birds regulate their salt balance.

29. Draw and label a mammalian nephron. For each division you label, indicate what goes on there in the formation of urine. Describe the function of Bowman's capsule, proximal tubule, distal tubule, loop of Henle, and the collecting duct of a nephron.

30. What is the advantage of ultrafiltration? How does it work? What is “primary urine”, and how does it differ from definitive urine that is eliminated from the body.

31. Define the glomerular filtration rate (GFR). Why is inulin used to measure GFR?

32. What is renal clearance? What are the expected values for substances that are filtered only? Filtered and resorbed? Filtered and secreted?

33. What is the transport maximum (=tubular resorption maximum)? What happens when it is exceeded (in case of glucose)? The majority of glucose, amino acids, water and salts are reabsorbed in what section of the nephron?

34. The active transport of NaCl that is key for maintaining the medullary osmotic gradient (which in turn “drives” the concentration of urine) occurs in which section of the nephron?

35. How is urine concentrated in mammals? Show how the countercurrent multiplier of the loop of Henle produces an osmotic gradient, and how that gradient is used in the formation of hyperosmotic urine. What two properties of the ascending limb of the loop of Henle tubule are responsible for the resulting concentrated urine? Explain how the different properties of the ascending and descending Loop of Henle are important for urine formation. What is function of the Na+/K+ pump in the formation of urine?

36. What is the vasa recta? What is its role in urine formation?

37. Understand renal regulation of sodium and water

1. Wiggers Diagram and Cardiac Cycle: The Wiggers diagram illustrates the various phases of the cardiac cycle and the corresponding electrical and mechanical events. During the cardiac cycle, electrical changes precede mechanical changes. Electrical events, represented by the PQRST complex in an electrocardiogram (ECG), correspond to depolarization and repolarization of the heart chambers. Pressure changes occur within the heart chambers, reflecting the opening and closing of valves and the contraction and relaxation of the myocardium. For instance, during systole, ventricular pressure rises, leading to the ejection of blood into the pulmonary and systemic circulation. During diastole, ventricular pressure decreases, allowing for the relaxation of the heart chambers and the filling of blood from the atria.

2. Pressure-Volume Loop: A pressure-volume (PV) loop describes the relationship between pressure and volume within the heart during one complete cardiac cycle. As the ventricles contract (systole), pressure increases rapidly while volume decreases, representing ejection of blood. During relaxation (diastole), pressure decreases as the ventricles fill with blood, leading to an increase in volume. The loop allows visualization of ventricular function and can indicate changes in contractility, preload, and afterload.

3. Factors Influencing Stroke Volume: Stroke volume, the amount of blood ejected from the left ventricle in one contraction, is influenced by preload (end-diastolic volume), contractility (myocardial performance), and afterload (resistance to ejection). Additionally, heart rate and ventricular compliance can affect stroke volume.

4. Factors Determining Ventricular Preload: Ventricular preload refers to the degree of stretch of the cardiac muscle fibers just prior to contraction. It is determined by venous return to the heart, which is influenced by factors such as blood volume, venous tone, and cardiac filling time.

5. Inotropes and Chronotropes: Inotropes are agents that affect the force of myocardial contraction. They can increase or decrease contractility. Chronotropes, on the other hand, affect heart rate by altering the rate of depolarization in the heart's conduction system. Inotropes primarily act on myocardial contractility, while chronotropes primarily affect heart rate.

6. Regulation of Mean Arterial Pressure (MAP): The cardiovascular system maintains MAP by adjusting cardiac output and/or total peripheral resistance. Five major factors involved in regulation include:

   • Sympathetic nervous system: Increases heart rate and contractility, leading to increased cardiac output and vasoconstriction, which raises total peripheral resistance.

   • Parasympathetic nervous system: Decreases heart rate, reducing cardiac output.

   • Renin-angiotensin-aldosterone system: Regulates blood volume and systemic vascular resistance by controlling sodium and water retention and vasoconstriction.

   • Baroreceptor reflex: Detects changes in blood pressure and adjusts heart rate and vascular tone to maintain homeostasis.

   • Local factors: Autoregulation of blood flow in specific tissues through mechanisms such as metabolic vasodilation or myogenic responses.

7. Composition of Dry Air: Dry air typically contains approximately 21% oxygen, 78% nitrogen, and trace amounts of other gases, including carbon dioxide (~0.04%).

8. Variation in Air Composition: Factors such as altitude, temperature, and humidity can influence the fractional composition of air and total pressure. As altitude increases, the partial pressure of oxygen decreases due to lower atmospheric pressure. Changes in temperature and humidity affect the density and water vapor content of air, altering partial pressures accordingly.

9. Solubility of Gases in Water: Carbon dioxide dissolves more rapidly in water than oxygen due to differences in solubility coefficients and chemical properties. Carbon dioxide reacts with water to form carbonic acid, which readily dissociates into bicarbonate and hydrogen ions, enhancing its solubility compared to oxygen.

10. Effect of Temperature and Ionic Strength on Gas Solubility in Water: Generally, as temperature increases, gas solubility decreases. Ionic strength, such as in seawater, can affect gas solubility due to interactions with ions. Carbon dioxide is more soluble in water than oxygen, regardless of temperature or ionic strength.

11. Differences Between Air and Water in Respiratory Organs Design:

• Oxygen content: Air contains a higher concentration of oxygen compared to water, making it easier for organisms to extract oxygen for respiration.

• Viscosity: Water is denser and more viscous than air, requiring specialized respiratory structures to facilitate gas exchange.

• Diffusion rates: Gas diffusion occurs more slowly in water than in air due to its higher density and viscosity, necessitating larger respiratory surfaces.

12. Fish Gill Structure:

• Gill arches: Support structures that contain gill filaments.

• Gill filaments: Thin, finger-like projections covered in lamellae.

• Lamellae: Site of gas exchange, where oxygen is absorbed from water and carbon dioxide is released.

• Water flow: Typically flows over the gills in one direction, while blood flows in the opposite direction, facilitating efficient gas exchange via countercurrent exchange.

13. Fish Ventilation Mechanisms:

• Buccal pumping: Involves rhythmic opening and closing of the mouth, creating a pumping action to move water over the gills. Used during low activity or when additional oxygen is needed.

• Ram ventilation: Involves continuous swimming with the mouth open, allowing water to flow over the gills. More energy-efficient than buccal pumping as it utilizes forward movement to passively ventilate the gills.

14. Changes in Lung Volumes During Exercise:

• Tidal volume increases: Volume of air inspired and expired with each breath increases to meet increased oxygen demand.

• Inspiratory and expiratory reserves decrease: Reserve volumes decrease as tidal volume increases to accommodate higher respiratory demands.

15. Frequency of Breathing vs. Alveolar Ventilation Volume:

• Frequency of breathing: Refers to the number of breaths per minute.

• Alveolar ventilation volume: Refers to the volume of fresh air that reaches the alveoli per minute, calculated as the tidal volume minus dead space volume multiplied by breathing frequency. Increasing tidal volume improves alveolar ventilation rate more effectively than increasing breath frequency.

16. Hypoventilation and Hypercapnia:

• Hypoventilation: Inadequate ventilation leading to decreased removal of carbon dioxide (CO2) from the lungs. This results in an accumulation of CO2 in the blood, leading to hypercapnia.

• Hypercapnia: Elevated levels of CO2 in the blood. CO2 reacts with water to form carbonic acid, which dissociates into bicarbonate ions and protons, lowering blood pH and causing respiratory acidosis.

17. Regulation of Ventilation Rate in Air Breathers:

• Chemoreceptors: Carotid and aortic bodies sense changes in arterial blood pH, oxygen, and CO2 levels, adjusting ventilation accordingly.

• Pulmonary stretch receptors: Located in the lungs, they regulate the depth and frequency of breathing to prevent overinflation.

• Phrenic nerve: Innervates the diaphragm, playing a key role in controlling respiratory rhythm and depth. Discharge activity of the phrenic nerve is enhanced by high alveolar PCO2, stimulating increased ventilation.

• Brainstem: Respiratory centers in the medulla and pons coordinate inspiratory and expiratory neuron activity, modulating breathing patterns.

18. Functions of Respiratory Pigments:

• Oxygen transport: Respiratory pigments bind and transport oxygen from respiratory surfaces to tissues.

• Carbon dioxide transport: Facilitate the transport of carbon dioxide from tissues to respiratory surfaces for elimination.

• Buffering: Help maintain pH balance by binding and releasing protons as needed.

19. Factors Affecting Oxygen Binding Affinity:

• P50 value: Indicates the partial pressure of oxygen at which hemoglobin is 50% saturated. A higher P50 indicates lower oxygen affinity.

• pH: Decreased pH (acidosis) reduces oxygen affinity (Bohr effect), while increased pH (alkalosis) enhances oxygen affinity.

• Organic phosphates: DPG (diphosphoglycerate) and inositol triphosphate reduce hemoglobin's affinity for oxygen.

• CO bound to Hb: Carbon monoxide competes with oxygen for binding sites on hemoglobin, reducing oxygen transport capacity.

• Altitude adaptation: Organisms at high altitude often increase DPG production to enhance oxygen unloading at tissues, compensating for lower atmospheric oxygen pressure

20. Forms of CO2 Transport in Blood Plasma:

• Bicarbonate (HCO3-): The majority of CO2 in blood plasma is in the form of bicarbonate ions, which result from the hydration of CO2 catalyzed by carbonic anhydrase within red blood cells.

• Molecular CO2: Some CO2 is dissolved directly in the plasma.

• CarbaminoHb: A small fraction of CO2 binds directly to hemoglobin to form carbamino compounds.

21. Conversion of CO2 to Bicarbonate and Role of Carbonic Anhydrase:

• CO2 is converted to bicarbonate (HCO3-) in red blood cells through the hydration of CO2 catalyzed by carbonic anhydrase.

• This reaction generates bicarbonate ions and protons (H+).

• In tissues, where CO2 levels are higher, this reaction drives the production of bicarbonate ions, facilitating CO2 removal.

• In the lungs, where CO2 levels are lower, the reaction shifts to the left, favoring the production of CO2 for exhalation.

22. Bohr and Haldane Effects:

• Bohr effect: Describes the influence of pH on the oxygen-binding affinity of hemoglobin. Lower pH (acidosis) reduces hemoglobin's affinity for oxygen, promoting oxygen release at tissues.

• Haldane effect: Describes the influence of oxygen saturation on CO2 binding affinity. Deoxygenated hemoglobin binds CO2 more readily than oxygenated hemoglobin, facilitating CO2 transport from tissues to lungs.

23. Comparison of Fluid Compartments:

• Intracellular fluid (ICF): Fluid within cells, comprising about 2/3 of total body water.

• Extracellular fluid (ECF): Fluid outside cells, divided into plasma (fluid portion of blood) and interstitial fluid (fluid surrounding cells), comprising about 1/3 of total body water.

• Major non-electrolytes contributing to osmolarity include glucose, urea, and organic acids

24. Factors Affecting Water/Ion Exchange and Desiccation:

• Surface area to volume ratio: Animals with a smaller surface area to volume ratio tend to desiccate slower due to reduced surface area for water loss.

• Metabolic water: Produced during cellular respiration, metabolism of fats yields more metabolic water than metabolism of carbohydrates.

• Other factors include environmental humidity, temperature, and the efficiency of excretory organs in regulating water and ion balance.

25. Ionic Composition of Freshwater vs. Seawater:

• Freshwater typically contains lower concentrations of ions such as sodium, chloride, and magnesium compared to seawater.

• Seawater has a higher salt concentration, predominantly sodium and chloride ions, due to evaporation and the influx of dissolved minerals from land.

26. Osmoregulation in Marine Organisms:

• Osmoconformers: Maintain internal osmolarity similar to that of their environment, allowing ions to passively diffuse across permeable membranes. Examples include marine invertebrates like jellyfish.

• Osmoregulators: Regulate internal osmolarity independently of their environment, actively controlling ion and water balance. Examples include marine teleost fish.

27. Osmolytes in Elasmobranchs:

• Elasmobranchs, such as sharks and rays, maintain high osmolarity of body fluids through the accumulation of urea and trimethylamine oxide (TMAO), which act as osmolytes to balance osmotic pressure with the surrounding seawater.

28. Salt Balance in Marine Reptiles and Birds:

• Marine reptiles and birds excrete excess salts through specialized salt glands located near the nasal passages or eyes.

• These glands actively secrete concentrated salt solutions, allowing the animals to maintain proper salt balance despite their hyperosmotic environment.

29. Mammalian Nephron Structure and Function:

• Bowman's capsule: Site of ultrafiltration where blood is filtered to form primary urine.

• Proximal tubule: Reabsorption of ions, glucose, amino acids, and water from the filtrate.

• Loop of Henle: Establishes osmotic gradient in the medulla, contributing to concentration of urine.

• Distal tubule: Further reabsorption of ions and water under hormonal control.

• Collecting duct: Regulates water reabsorption and urine concentration, influenced by antidiuretic hormone (ADH).

30. Advantages of Ultrafiltration:

• Ultrafiltration separates plasma from blood cells and proteins, allowing small molecules such as water, ions, and nutrients to pass into the renal tubules for further processing.

• Primary urine, formed through ultrafiltration, contains waste products and excess substances that need to be excreted from the body.

31. Glomerular Filtration Rate (GFR):

• GFR is the rate at which fluid is filtered through the glomerulus into Bowman's capsule per unit of time.

• Inulin, a substance not reabsorbed or secreted by the kidneys, is used to measure GFR because it provides an accurate reflection of renal filtration function.

32. Renal Clearance:

• Renal clearance is the volume of plasma from which a substance is completely removed by the kidneys per unit of time.

• Substances that are filtered but not reabsorbed or secreted have a renal clearance equal to the GFR.

• Substances that are filtered and reabsorbed have a lower renal clearance, while those that are filtered and secreted have a higher renal clearance.

33. Transport Maximum and Tubular Resorption:

• Transport maximum (Tm) refers to the maximum rate of reabsorption for a particular substance by renal tubules.

• When Tm is exceeded, the substance appears in the urine (e.g., glucose in diabetes).

• Glucose, amino acids, water, and salts are primarily reabsorbed in the proximal tubule of the nephron.

34. Active Transport in Maintaining Medullary Osmotic Gradient:

• Active transport of sodium chloride (NaCl) occurs in the thick ascending limb of the loop of Henle.

• This process, facilitated by the Na+/K+/2Cl- symporter, pumps ions out of the tubule into the interstitial space of the renal medulla.

• The establishment of a high concentration of ions in the medulla creates an osmotic gradient, essential for water reabsorption in the collecting ducts and concentration of urine.

35. Urine Concentration Mechanism in Mammals:

• Countercurrent Multiplier System: Occurs in the loop of Henle where the descending limb is permeable to water but not ions, while the ascending limb is impermeable to water but actively transports ions out.

• Properties of Loop of Henle: The descending limb allows passive reabsorption of water, concentrating the tubular fluid. The ascending limb actively transports ions out, creating a hypertonic medullary interstitium.

• Role of Na+/K+ Pump: Maintains the ion gradient necessary for active transport in the ascending limb, contributing to the hypertonic medullary interstitium and facilitating water reabsorption in the collecting ducts.

36. Vasa Recta:

• The vasa recta are peritubular capillaries that run parallel to the loop of Henle in the renal medulla.

• They play a crucial role in maintaining the osmotic gradient by allowing exchange of solutes and water without disrupting the concentration gradient.

• The vasa recta prevent the washout of ions and maintain the hypertonic environment necessary for urine concentration.

37. Renal Regulation of Sodium and Water:

• Sodium regulation: Regulated by aldosterone, which increases sodium reabsorption in the distal tubules and collecting ducts, thereby increasing water retention and blood volume.

• Water regulation: Regulated by antidiuretic hormone (ADH), which increases water reabsorption in the collecting ducts, concentrating urine and reducing water loss.

These mechanisms collectively maintain electrolyte balance, blood pressure, and osmolarity within narrow physiological ranges.