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CASE STUDY CONCEPTS

Each Case Study has been researched and crafted to provide the maximum learning potential for physiology students at every education level. Case Studies allow individual users to explore a wide range of physiological systems. Creating graphs and watching the physiological changes happening in real-time grants an unparalleled learning experience. Below are some of the Case Studies and their associated targeted learning concepts:

Acid-base regulation

  • pH defined, blood pH normally with a narrow range
  • Carbonic acid, bicarbonate buffer
  • Experiment: The effect of hyperventilation on pH
  • Experiment: Respiratory acidosis
  • Experiment: Respiratory alkalosis
  • Experiment: Metabolic acidosis
  • Experiment: Relationship between inspired CO2 and arterial bicarbonate
  • Acute respiratory acidosis: arterial pH & arterial HCO3-
  • Davenport acid-base diagram
  • Acute metabolic acidosis: interpret graph of arterial HCO3- versus arterial pH
  • Acute metabolic alkalosis: interpret graph of arterial HCO3- versus arterial pH

Baroreceptor reflex

  • Baroreceptor reflex, orthostatic hypotension (postural hypotension)
  • Experiment: Calculation of pulse pressure from systolic and diastolic pressures
  • Experiment continued: Calculation of MAP using formula (compare model value with calculated value)
  • Experiment continued: Measure heart rate
  • Experiment continued: Effect of lying to standing transition on cardiovascular system with baroreceptor reflex input intact
    • Carotid pressure, baroreceptor nerve activity, sympathetic nerve activity
  • Experiment: Effect of drug midodrine, a vasoconstrictor, on cardiovascular parameters
  • Experiment: orthostatic hypotension (Task: find a good way to recreate the disease in the simulation)
  • Treating orthostatic hypotension (Task: Try 3 different treatments to find the one that works best)

Control of blood flow

  • Cardiac output (CO = SV × HR)
  • Experiment: Effect of exercise on cardiovascular output (CO)
  • Experiment continued: Baseline CO
  • Experiment continued: Basal metabolism
  • In practice, metabolism is often measured by recording the rate of O2 consumption
  • Experiment continued: Increase in metabolism with exercise
  • Metabolic scope defined
  • Experiment continued: Skeletal muscle blood flow during exercise
  • Experiment continued: Increased cardiac output during exercise
    • During exercise, heart rate and stroke volume both increased, contributing to the increase in cardiac output.
  • Experiment: measure CO, HR, and SV during exercise
  • Experiment: Do a linear regression in Excel with data exported from Just Physiology.
  • Total peripheral resistance
  • CO = (MAP – PRA)/TPR; where PRA is the mean pressure in the right atrium.
  • The increase in CO during exercise is largely due to a decrease in TPR.
  • The body controls MAP by regulating CO and TPR.
  • Decrease in TPR due to increase in blood vessel diameter
  • Experiment: Measure change in blood flow to muscle, bone, kidneys, brain, skin, and GI tract from resting state to exercising state.
    • Some organs decrease their blood flow during exercise, others increase their blood flow.
  • Local control of blood vessel dilation
  • The ANS shunts some blood flow away from specific vascular beds during exercise
  • An increase in blood flow to the skin helps to dissipate heat.

Control of ventilation

  • Tidal ventilation
  • Conducting zone and respiratory zone
  • Diaphragm
  • Inspiration
  • Expiration
  • Total lung capacity
  • Tidal volume
  • Dead space
  • Calculate: Alveolar volume = volume of lung at end of inspiration – dead space
  • Calculate: Alveolar volume exchanged per breath
  • Functional residual capacity defined
  • Inspiratory reserve capacity defined
  • Vital capacity defined
  • Forced expiratory volume defined
  • FEV1 / FVC; Calculate the percentage given data.
  • Experiment: Control of tidal volume during exercise
  • Experiment continued: Control of ventilatory rate during exercise
  • Calculate alveolar ventilation [Alveolar Ventilation = (Tidal Volume - Dead Space) x (Respiratory Rate)]
  • Calculate the ratio of dead space volume to tidal volume during rest and during exercise.
  • The respiratory center in the brainstem
  • Central & Peripheral chemoreceptors
  • The relationship between inspired PO2 and total ventilation
  • The relationship between inspired PCO2 and total ventilation

Homeostasis 1: ANS

  • Intro to the autonomic nervous system (ANS)
  • The “fight-or-flight response” and the “rest and digest” response
  • The sympathetic nervous system (SNS) and the parasympathetic nervous system (PNS)
  • Blood pressure is an important determinant of tissue perfusion.
  • Positive versus negative feedback
  • Mean arterial pressure (MAP) defined
  • Experiment: SNS and PNS inputs affect MAP
  • Experiment: Effect of Hemorrhage on blood pressure
  • Experiment: Hemorrhage challenge (Keep patient alive by monitoring and altering SNS and PNS input.)
  • Experiment: Positive correlation between SNS activity and heart rate
  • Experiment continued: Negative correlation between PNS activity and heart rate
  • Correlation does not prove that the autonomic nervous system controls heart rate.
  • Experiment: Manipulate SNS and PNS activity by clamping them to different levels. Observe the resulting changes in heart rate.
  • Choose the correct block diagram showing inputs that influence heart rate.

Homeostasis 2: Cardiovascular center

  • This case study follows “Homeostasis 1: ANS Control of Heart Rate”.
  • The autonomic nervous system (review diagram and text).
  • SNS affects stroke volume and heart rate; PNS affects only heart rate.
  • Increases in stroke volume and/or heart rate lead to an increase in blood pressure and tissue perfusion
  • Experiment: The effects of SNS and PNS activity on blood pressure.
  • Experiment: Compensatory responses of the SNS and PNS
    • (decrease one branch of the ANS without clamping the other).
  • Experiment: Test the hypothesis that a 50% decrease in SNS activity is normally compensated for by an decrease in PNS activity due to the drop in blood pressure.
  • Cardiovascular center: identify the relationship between blood pressure and neural activity in the cardiovascular center on block diagram.
  • Feedback to the PNS and SNS from the cardiovascular center, which receives input from baroreceptors, prevents a sudden decrease in SNS activity from having a lasting effect on blood pressure.

Homeostasis 3: Baroreceptors

  • This case study follows “Homeostasis 2: Cardiovascular center”.
  • Baroreceptors are described.
  • Baroreceptor locations
  • Block diagram shown that now includes the baroreceptors.
  • Experiment: In response to a decrease in carotid sinus pressure baroceptor activity decreases. In turn, SNS activity increases. Vagal firing decreases. Heart rate increases.
  • Students are asked to predict the relationship between arterial pressure and baroreceptor activity.
  • Experiment: Generate baroreceptor response curves
  • Experiment: Baroreceptor adaptation simulation
  • Baroreceptor adaptation possible link to hypertension

Homeostasis 4: Chemoreceptors

  • This case study follows “Homeostasis 3: Baroreceptors”.
  • Central and peripheral chemoreceptors are described
  • CO2 + H3O ⇋ H+ + HCO3-
  • Change in [H+] in response to an increase in CO2
  • The effect of an increase in tissue perfusion on tissue PO2, PCO2, H+
  • Experiment: O2-chemoreceptor
    • Alter the O2 percentage of inhaled gas; measure the O2 chemoreceptor activity.
  • Experiment continued: Plot O2 chemoreceptor activity versus arterial PO2
  • Experiment continued: Plot SNS activity versus arterial PO2 and PNS activity versus arterial PO2
  • Experiment continued: Plot SNS activity versus O2 chemoreceptor activity
  • O2-chemoreceptor transduction
  • Experiment: CO2-chemoreceptor
  • Experiment continued: Plot chemoreceptor activity versus arterial PCO2
  • CO2-chemoreceptor transduction
  • The blood-brain barrier: How does a change in blood PCO2 affect central chemoreceptors, which are behind the blood-brain barrier?

Gas Exchange

  • Atmospheric gases
  • Calculate partial pressure
  • Calculate partial pressure, accounting for water vapor
  • Calculate partial pressure, accounting for altitude and water vapor
  • Basal metabolism (O2 consumption as a good proxy measure of aerobic metabolism)
  • Experiment: Respiratory exchange ratio
  • Fick’s 1st law of diffusion
  • Gas diffusion
  • Alveoli
  • Maximizing gas diffusion
  • Zones of the mammalian lung
    • The conducting zone
    • The respiratory zone
  • Dead space
  • Experiment: Changes in gas composition between inspired and alveolar gas
  • Experiment continued: Alveolar gas exchange
  • Experiment continued: Venous shunt
  • Experiment continued: CO2 exchange
  • Experiment continued: A paradox in O2 and CO2 capacities
  • Dissolved CO2 in Blood; Henry’s Law
  • CO2 transport as bicarbonate
    • CO2 + H3O ↔ H3CO3 ↔ H+ + HCO3-
  • Carbonic anhydrase
  • O2 transport
    • Hemoglobin
  • Calculate number of moles of O2 per liter of blood.
  • The O2 dissociation curve.
  • Percent saturation
  • The P50 indicates affinity
  • Increased P50 indicates decreased affinity
  • Venous Blood has a decreased O2 affinity
  • O2 saturation of blood returning from the body
  • The difference between PO2 and PO2 concentration in the blood
  • Experiment: Effects of exercise on gas exchange
  • Changes in blood PO2 with moderate exercise: Decrease in pulmonary artery PO2
  • Cardiac output
  • The Fick Principle
  • The Fick Principle and cardiac output
  • Arteriovenous oxygen difference
  • Calculation of cardiac output
  • Hemoglobin affinity and exercise (Bohr Effect)
  • Shift in the O2-dissociation curve
  • Experiment: Effect of Altitude on O2 delivery to tissues
    • Rapid ascent
  • Experiment continued: The relationship between arterial O2 concentration and inspired PO2.
  • Decreased arterial PCO2 at altitude (Bohr Effect, left-ward shift in O2-dissociation curve)
  • Short-term changes in hematocrit are due to the movement of water between fluid compartments of the body.
  • The CO2—bicarbonate reaction
  • Respiratory alkalosis at high altitude due to increased ventilation

Glucose homeostasis: short-term

  • Intake of fuel and nutrients
  • Blood glucose
  • Experiment: Fast
    • Measure plasma [glucose], basal metabolic rate
  • Experiment continued: insulin and glucagon response to fast (decrease in blood glucose)
  • Experiment continued: Find the correlations between Insulin concentration and plasma [glucose], and glucagon concentration and plasma [glucose].
  • Experiment: The glucose tolerance test
  • Where did the infused glucose go?
    • Plot liver glycogen storage, muscle glycogen storage, total lipid stores, cellular protein
  • Glucose homeostasis: Type 1 diabetes
  • Experiment: Fasting with type 1 diabetes mellitus
  • Glucagon release
  • Experiment: Glucose tolerance test in subject with type 1 DM
  • Metabolic energy sources during starvation

Glucose homeostasis: long-term

  • This lesson follows “Glucose homeostasis: short-term”.
  • Metabolic energy sources
  • Experiment: long-term starvation (simulation of starvation for 5 days)
    • Energy stores: glycogen, adipose tissue lipids, and cell protein
  • Experiment continued: Insulin response to starvation
  • Daily Insulin fluctuations
  • Experiment continued: Glycogen metabolism during starvation
  • Gluconeogenesis
  • Basal metabolism
  • Experiment continued: lipid and protein catabolism
  • Ketoacidosis
  • Experiment: Lipid metabolism in type 1 diabetes mellitus
  • Experiment: measure blood ketoacid concentration.
  • Diabetic ketoacidosis
  • Experiment: Treating a patient with diabetic ketoacidosis

Physiological integration

  • This lesson follows “Control of Blood Flow”
  • Cardiac output (CO), Mean arterial pressure (MAP)
    • CO = HR × SV; MAP = CO × TPR
  • Heart rate regulation by the autonomic nervous system
  • The regulation of total peripheral resistance (TPR) by:
    • local control of the diameter of arterioles
    • central regulation by the sympathetic nervous system
  • The cardiovascular center
  • Integrating HR, SV, CO, and TPR; Block diagram
  • Large block diagram with many blanks. As progress is made the blanks will be filled in.
  • Experiment: Hemorrhage
    • Plot change in MAP after 1000 mL of blood loss
    • Plot change in cardiac output
  • Experiment continued: plot changes in HR, SV, and TPR after hemorrhage
  • Distinguish between direct effects of the hemorrhage versus compensatory responses
  • Determine how TPR and HR help to maintain MAP during hemorrhage.
  • Arteriole tone and TRP
  • TPR response to hemorrhage
  • Calculate the change in the blood vessel radius necessary to alter TPR by a certain amount using Poiseuille’s law
  • Selectivity of the vascular response
  • SV depends on End-diastolic volume (EDV) and end-systolic volume (ESV)
  • SV = (EDV - ESV)
  • EDV depends on venous return
  • Determine what factor leads to a decrease in EDV during hemorrhage
  • Capacitance and venous pressure
  • Venous tone
  • Skeletal-muscle pump
  • Respiratory pump
  • Effects propagating from the right to left side of the heart
  • Linking SNSA to ESV
  • Determine Factors affecting ESV
  • Heart contractility
  • Calculate ejection fraction (SV/EDV)
  • Sensory inputs to the cardiovascular system
  • Baroreceptors
  • Experiment: Regulation of conductance during hemorrhage
    • Arrange a number of tissue beds in order of percent decrease in conductance
  • Sending blood to the most sensitive tissues
  • Blood distribution in the vascular system
  • Experiment: Regulation of blood distribution
    • Find the percent change in volume of different parts of the circulatory system.
  • Veins and venules as blood reservoirs
    • A change in venous capacitance can transfer blood to other parts of the circulatory system.
  • Getting blood to the brain
  • Testing for orthostatic changes
  • Experiment: Postural adjustments
    • The hemorrhage subject is forced into a standing posture.
  • Experiment: Blood volume recovery
    • Short-term and long-term recovery
  • Components of blood
  • Hematocrit
  • Regulating GFR, water loss, and electrolyte loss
  • Regulation of renin release
  • Renin-angiotensin-aldosterone system
  • Osmoreceptors
  • Baroreceptor control of ADH release
  • Regulation of ECF volume and osmolarity
  • SNS control of the RAAS
  • Recovery: 24 h, Long-term
  • Dilution of the blood
  • The importance of tissue perfusion
  • Secretion of erythropoietin
  • Feedback control of erythropoietin release
  • Complete recovery (all banks in block diagram are filled in)

Pressure-flow 1: Introduction

  • Resistance
  • Hydrostatic pressure
  • Flow = pressure / resistance
  • Simple cardiovascular model.
  • Cardiac output is the blood flow
  • Rearrange the flow equation to solve for pressure
    • Blood Pressure = Cardiac Output × Vascular Resistance
  • How can cardiac output compensate for a change in vascular resistance?

Pressure-flow 2: Regulation

  • Organization of the autonomic nervous system (diagram)
  • Blood pressure and feedback
  • Experiment: Autonomic regulation of mean arterial pressure (MAP)
    • Determine how SNS and vagal inputs affect MAP
  • Pressure and resistance during exercise
  • A decrease in resistance allows for an increase in flow though the vascular bed of specific tissues
  • Experiment: Effect of exercise on MAP
  • Regulation of MAP during exercise
    • SNS rate and vagal rate
  • Experiment continued: Determine how MAP in maintained in a normal range during exercise.
    • Manipulate SNS activity and PNS activity; Plot cardiac output
  • Cardiac output = stroke volume × Heart Rate
  • Experiment: Explore how SNS and vagal inputs affect stroke volume
  • Autonomic regulation of heart rate
    • Manipulate SNS activity and PNS activity; Plot heart rate
  • Feedback from MAP affects SNS and PNS activity

Pressure-flow 3: CV Circuit Model

  • Hydrostatic pressure
  • Flow and resistance
  • Ohm’s law
  • Resistors in parallel
  • Hagen-Poiseuille equation
  • Organization of the cardiovascular system
  • Electric circuit model of the systemic circulation
  • Driving pressure of the systemic circulation
  • Cardiac output, flow, and current

Receptor-Ligand Binding

  • Ligand defined
  • Hormones defined
  • Hormone receptors
  • Binding capacity
  • The dissociation constant, KD
  • Differential ligand-receptor affinity in the human body

Renin-Angiotensin system

  • RAS explained.
  • Renin, angiotensin II, aldosterone
  • Experiment: increased NaCl intake
  • Experiment: increased NaCl intake, while angiotensin II is kept at a fixed concentration of 12 pg/ml

Water and Solute Distribution

  • Total water, ICF, and ECF
  • Experiment: Determine the body water distribution between various fluid compartments of the body.
  • Experiment continued: Water as a percentage of total body mass
  • Experiment continued: ICF as a percentage of total body water
  • Water distribution in major compartments
  • Intravascular, extravascular, interstitial
  • Water distribution in special compartments
  • Osmolarity
  • Osmotic coefficient
  • Osmosis
  • Active osmoles
  • Water moves relatively freely between the fluid compartments of the body.
  • Experiment: Water infusion
    • Determine how the water becomes distributed in the fluid compartments of the body in the short-term (2 min).
    • Determine how the water becomes distributed in the fluid compartments of the body in the long-term (1 h).
  • Water follows osmotically active particles
  • Calculate the total number of osmoles of various ionic species in particular fluid compartments of the body.
  • Ionic composition of the fluid compartments
  • Ion pumps maintain the gradients
  • Physiological saline solution
  • Experiment: Saline infusion
  • Hypertonic saline solution
  • Experiment: Hyperosmotic infusion