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Physiology Final Assignment
Cholesterol is essential to the normal function of our bodies, but too much cholesterol negatively affects health. Cholesterol circulates in the blood, where it accumulates on the walls of arteries and limits the flow of blood. If cholesterol blocks blood vessels severely, a person can suffer a heart attack or a stroke. Two forms of cholesterol contribute to the total concentration in the blood: high-density lipoprotein (HDL cholesterol) and low-density lipoprotein (LDL cholesterol). HDL cholesterol is absorbed by cells of the liver and used to convert cholesterol into bile salts, which can be excreted from the body through the intestines. LDL cholesterol, however, can accumulate in the walls of arteries, narrowing the path for blood flow and increasing blood pressure. Therefore, doctors closely monitor the concentration of LDL cholesterol in the blood of their patients. In the United States, a concentration of cholesterol greater than 190 mg dL-1^ would be considered very high. A patient with a high concentration of LDL cholesterol would be treated to prevent heart disease and related illnesses.
Scenario
You are a member of a committee formed to review recommendations for standard medical treatments. Your subcommittee has been assigned to evaluate two common dietary treatments for people with a high concentration of LDL cholesterol - a diet low in cholesterol or a diet low in saturated fats. Additionally, we need your subcommittee to evaluate and recommend an appropriate dose of a drug called a statin, which has been shown to help reduce LDL cholesterol. To complete this assignment, take the following steps: Step 1: Determine how the concentration of LDL cholesterol might exceed the maximum recommended for health. Step 2: Determine which diet better reduces the concentration of LDL cholesterol in a person's blood.
Step 3: Evaluate how statins help to reduce the concentration of LDL cholesterol in a person's blood and recommend an appropriate dose of a statin.
There is an arrow pointing from the variable “Rate at which cholesterol is ingested” to the regulated variable “Concentration of LDL cholesterol in the blood” with a “+” symbol over it. There is an arrow pointing from the regulated variable - “Concentration of LDL cholesterol in the blood” - to the variable “Activity of cholesterol receptors in membranes of liver cells” with a “+” symbol over it, from the variable “Activity of cholesterol receptors in membranes of liver cells” to the variable “Rate of transport of cholesterol into liver cells” with a “+” symbol over it, from the variable “Rate of transport of cholesterol into liver cells” to the variable “Rate at which enzymes in the liver convert cholesterol to bile salts” with a “+” symbol over it, and from the variable “Rate at which enzymes in the liver convert cholesterol to bile salts” to the regulated variable “Concentration of LDL cholesterol in the blood” with a “-” symbol over it. There is an arrow pointing from the regulated variable - “Concentration of LDL cholesterol in the blood” - to the variable “Activity of cholesterol receptors in membranes of non-liver cells” with a “+” symbol over it, from the variable “Activity of cholesterol receptors in membranes of non-liver cells ” to the variable “Rate at which non-liver cells import cholesterol” with a “+” symbol over it, from the variable “Rate at which non-liver cells import cholesterol” to the variable “Rate at which non-liver cells produce cholesterol” with a “-” symbol over it, from the variable “Rate at which non-liver cells produce cholesterol” to the variable “Rate at which non-liver cells export cholesterol” with a “+” symbol over it, and from the variable “Rate at which non-liver cells export cholesterol” to the regulated variable “Concentration of LDL cholesterol in the blood” with a “+” symbol over it. Analyze the path model in Figure 1 to determine what could cause a high concentration of LDL cholesterol in a person's blood. Directions : Use the path model of the homeostatic system that regulates the concentration of LDL cholesterol (Figure 1) to answer questions 1-8.
- True or False: A decrease in the activity of cholesterol receptors in the membranes of liver cells would increase the concentration of LDL cholesterol in the blood. true
- Explain your answer to the previous question. Your explanation should minimally discuss why the specified failure of the homeostatic system would (or would not) increase the concentration of LDL cholesterol. The decrease of the activity of the cholesterol receptors in the membranes would actually decrease the concentration of LDL
cholesterol in the blood
- True or False: An increase in the rate at which non-liver cells import cholesterol would increase the concentration of LDL cholesterol in the blood.
To answer this question, you must determine whether the concentration of cholesterol in a person's blood depends on the amount of cholesterol or the amount of saturated fats in
their diet. You have access to data from an experiment, in which 50 people with very high concentrations of LDL cholesterol followed a controlled diet for 3 months. Individuals were assigned to one of two treatments: 1) a diet low in cholesterol, or 2) a diet low in saturated fats. A sample of blood was taken from each person at the beginning and at the end of the experiment. The concentration of LDL cholesterol in each blood sample was measured using a standard protocol. Researchers then calculated the change in LDL cholesterol (Δ) for each person by subtracting the initial concentration from the final concentration: Δ = C 2 - C 1 where: C 1 = concentration of LDL cholesterol at the beginning of the experiment C 2 = concentration of LDL cholesterol at the end of the experiment A positive change reflects an increase in the concentration of LDL cholesterol, whereas a negative change reflects a decrease in the concentration of LDL cholesterol. Using the data from this experiment, determine which diet more effectively lowers the concentration of LDL cholesterol in a person’s blood. We’ll start by modeling the data from the experiment. Directions : For Questions 9-13, download the Excel file "Effect of Diet on LDL Cholesterol" in Canvas containing the data (sample size = 50 people per treatment group). Use Excel for calculations, modeling, and graphing. Round all calculated values to the nearest tenths of a decimal place. For example, if you calculate the value as 3.821853, you would round your answer to 3.8.
- Create a plot of a linear relationship between the type of diet (categorical variable: low cholesterol vs. low saturated fat) and the change in the concentration of LDL cholesterol (continuous variable: mg dL-1). Formatting Instructions
size = 18 ● Make sure the viewer can distinguish between the two treatments when looking at the figure. ● Y-axis and X-axis numbers: Font size = 14 ● Make sure the minimum and maximum bounds for your axes are reasonable. ● Provide tick marks for your axes where possible and appropriate. Marker ( If your figure has markers ) ● Make sure that your markers are clearly visible Error bars ( If your data enables you to estimate the standard deviation ) ● Direction: Both ● End style: Cap ● Error amount: Custom → Select the appropriate cell in Excel. ● Line: Solid line ● Color: Black ● Width: 0.75 pt
- Based on the figure that you created for the previous question, how does the type
of diet affect the change in the concentration of LDL cholesterol in a person's blood? A diet of low saturated fat decreases the concentration of LDL in the blood considerably more than a low cholesterol diet
- Estimate the standard deviation of the linear relationship between the type of diet and the change in the concentration of LDL cholesterol. Standard deviation = 21.
- Estimate the mean change in the concentration of LDL cholesterol for a person who followed the low cholesterol diet. Mean change in the concentration of LDL cholesterol = -1.
- Estimate the mean change in the concentration of LDL cholesterol for a person who followed the low saturated fat diet. Mean change in the concentration of LDL cholesterol =-12. Now, you are ready to construct an argument about whether a diet low in cholesterol or a diet low in saturated fats is more effective at lowering the concentration of LDL cholesterol in a person’s blood. Directions : Using the data you analyzed in questions 14-15, evaluate the two diets and recommend which one would be a better treatment for reducing high LDL cholesterol in a person. Be sure to provide your reasoning, highlighting the relevant evidence supporting your claim.
- Construct a claim that answers the question “Which diet (low cholesterol or low saturated fat) would more effectively reduce the concentration of LDL cholesterol in a person's blood?” A low saturated fat diet would be more effective at reducing the concentration of LDL cholesterol in a person’s blood.
Figure 2. Path model of the homeostatic system regulating LDL cholesterol in humans. Key components, variables, and relationships have been highlighted to help determine the appropriate dose of drug needed to help reduce a person’s LDL cholesterol when it is too high. Four components and their variables have been highlighted - the dose of the drug, the rate of transport of cholesterol into liver cells, the rate at which enzymes in the liver convert cholesterol to bile salts, and the concentration of LDL cholesterol in the blood. The dose of the drug, the rate of transport of cholesterol into liver cells, and the rate at which enzymes in the liver convert cholesterol to bile salts are each represented by a black box containing black text. The concentration of LDL cholesterol in the blood is represented by a dashed black box containing black text. An arrow points from the dose of the drug to the rate of transport of cholesterol into liver cells. The slope of the relationship between these two variables is provided as blue text above the arrow connecting these variables. The slope of this relationship is 0.03 (g d-1)/(mg d-1). Another arrow points from the rate of transport of cholesterol into liver cells to the rate at which enzymes in the liver convert cholesterol to bile salts. The slope of the relationship between these two variables is provided as blue text above the arrow connecting these variables. The slope of this relationship is 0.95 (g d-1)/(g d-1). Finally, an arrow points from the rate at which enzymes in the liver convert cholesterol to bile salts to the concentration of LDL cholesterol in the blood. The slope of the relationship between these two variables is provided as red text next to the arrow connecting these variables. The slope of this relationship is -302 (mg dL-1)/(g d-1).
Before we determine the appropriate dose of statin to administer to decrease LDL cholesterol levels by a specified amount, let’s make sure we understand how statins reduce the concentration of LDL cholesterol in the blood. Directions : Use Figure 2 to answer question 16.
- Provide a step-by-step explanation of how statins reduce the concentration of LDL cholesterol in the blood. Your explanation should describe how each of the following variables in the path model change when a person takes a statin: (a) rate at which liver cells import cholesterol, (b) rate at which enzymes in the liver convert cholesterol into bile salts, and (c) concentration of LDL cholesterol in the blood. A dose of the drug increases the rate of transport of cholesterol by liver cells, which increases the rate at which enzymes convert cholesterol into bile salts, which effectively decreases the concentration of LDL cholesterol in the blood. A healthy concentration of LDL cholesterol falls in the range of 100-130 mg dL-1. A doctor might prescribe a statin if a person's concentration of LDL cholesterol reaches 190 mg dL-1. Given these guidelines, your goal is to determine the dosage of the drug needed to decrease the concentration of LDL cholesterol by -60 mg dL-1. Directions: Use the path model in Figure 2 to answer question 17. Round all calculated values to the nearest tenths of a decimal place. For example, if you calculate the value as 3.821853, round to 3.8. 17. What dosage of the drug (mg/d) must be administered to reduce LDL cholesterol in the blood by 60 mg dL-1? As a note, the drug has no effect on LDL cholesterol in the body at dosages of 4.0 mg d-1^ or less, so be sure to add 4.0 mg d-1^ to your final answer. Dosage of drug (mg/d) = 11
