Module 3: The Pathology Of Metabolic And Cardiovacular Diseases Flashcards
Metabolism
Metabolism is a term that describes the total balance of energy requirements of the body. Metabolism is the process by which macromolecules from our food is converted into energy. Our bodies need this energy to do everything from moving to thinking to growing.
Metabolism describes how our bodies:
* Take in macromolecules,
* Store macromolecules,
* Break macromolecules down for energy/recycling, and
* Create new macromolecules as they are needed.
When one or more of these processes are disturbed, it can lead to a metabolic disorder
Metabolic Pathways
Anabolic
Anabolic pathways create new, more complex macromolecules out of smaller units or molecules. This process requires energy. Anabolic pathways are used by cells in our bodies to grow or to repair
damage.
Catabolic
Catabolic pathways break down macromolecules into smaller units or molecules, and generate energy
in the process
Macromolecules
Carbohydrates
- Includes sugars, glycogen, fiber, starches
- Simple (“bad”) vs. complex (“healthy”) carbs
- Glycogen → broken into glucose for energy
- Stored glycogen = first energy reservoir
Lipids
- Includes fats, oils, triglycerides, cholesterol
- Requires transporters (fats & water don’t mix)
- Stored in adipose tissue (fat cells)
- Second energy reservoir
Proteins
- Made of amino acid chains
- Central dogma: DNA → RNA → Protein
- Used for energy only in starvation
Nucleic Acids
- DNA & RNA (carry genetic info)
- Not used for energy
- Make ATP & GTP (energy molecules)
Factors that Influence Energy Storage
Food Intake
How much food you consume.
Food Expenditure
How much physical activity you get.
Fat Stores
How much fat you have stored.
C N S
Your basal metabolic rate (The number of calories required to keep your body functioning at rest. This rate
commonly varies between individuals.)
Hormones
Hormones are molecules that influence sensations such as hunger. They also signal whether macromolecules are stored or consumed, maintaining a balance between anabolic and catabolic pathways
Balance in Metabolism
Equilibrium
- Achieved when anabolism (building) and catabolism (breaking down) are balanced.
- The body continuously adjusts to maintain this state.
Anabolism (Storage Mode)
- Occurs with excess food intake & low activity.
- Converts sugars and fats into stored forms (glycogen & adipose tissue).
- Prolonged imbalance → weight gain, slower metabolism, increased fat storage.
Catabolism (Breakdown Mode)
- Triggered by exercise & fasting.
- Hormones signal for stored glycogen & fats to break down for energy.
- Sustained catabolism → weight loss, hunger, lower blood sugar.
Insulin
insulin is one such hormone involved in regulating metabolism. Insulin is a hormone produced by β-
cells, specialized cells in the pancreas. Insulin is responsible for maintaining healthy levels of glucose in
the blood. Recall that glucose is the preferred short-term fuel for most tissues
Relationship Between Insulin and Glucose
Insulin Binding
Insulin binds to the insulin receptor on the extracellular surface of cells. This leads to the activation of the receptor and signals which result in increases in anabolic activity.
Glucose Transport
At the same time, insulin stimulates the movement of glucose transporters from endosomes inside the
cell to the plasma membrane.
This allows glucose to enter the cell, and be used for energy.
No Insulin
When there is no insulin present, there are no glucose transporters on the plasma membrane. Therefore, glucose cannot enter the cell. Consequently, glucose cannot be metabolized
Chemical Properties of Lipids and Glucose
- Glucose is water-soluble and circulates in blood but requires transporters to enter cells.
- Lipids are not water-soluble and need transport proteins to move in blood.
- Unlike glucose, many lipids can enter cells without transporters.
Plasma Lipoproteins
- Lipids (cholesterol, triglycerides) need plasma lipoproteins for transport in blood.
- Lipoproteins form spherical complexes around lipids, making them water-soluble.
- Also assist in lipid absorption, ensuring delivery to the right locations.
- Play a minor role in lipid breakdown & synthesis as needed
Forms of Lipoproteins
LDL / Low Density Lipoproteins (“Bad” Cholesterol) → Transports cholesterol to tissues.
- Can build up in arteries → Heart disease & stroke risk.
- Keep LDL levels low (“L” for Lousy or Lower).
HDL / High Density Lipoproteins (“Good” Cholesterol) → Transports excess cholesterol back to the liver.
- Helps remove LDL from arteries.
- Keep HDL levels high (“H” for Healthy or Higher).
Triglycerides → Stored fats from excess diet intake.
- High levels = Increased cardiovascular disease risk.
- Managed by healthy diet, exercise, and lifestyle changes.
Obesity Epidemic
- Obesity = Excess body fat accumulation, classified as a metabolic disease.
- Evolutionary trait: Early humans stored fat for survival, but modern sedentary lifestyles & food abundance fuel obesity.
Rising Trends: - Childhood obesity in Canada tripled in 30 years.
- 2016: More obese adults than underweight globally.
- Health Risks: Increased risk of type 2 diabetes, cardiovascular disease, hypertension, cancer, and arthritis
Subcutaneous Fat
Location: Stored under the skin in the abdomen, hips, and thighs (80-90% of body fat).
Lower body fat (pear-shaped distribution):
- More common in biological females.
- Larger adipocytes, efficient at storing triglycerides.
- Mobilizes fat slower, leading to lower metabolic disease risk.
Visceral Fat
- Location: Stored inside the abdominal cavity, near the digestive tract (10-20% of body fat).
- High turnover rate & hormone-sensitive → More responsive to metabolic changes.
- Common in biological males, leading to apple-shaped obesity.
- Health Risks: Increased high blood pressure, insulin resistance, diabetes, & heart disease.
- Waist circumference is a key risk factor for metabolic disease monitoring.
Metabolic Syndrome
Metabolic syndrome (Met S) is a health disorder that greatly increases the risk of many chronic illnesses. Met S is diagnosed when a patient has at least three of the five risk factors.
Risk factors:
* Visceral Obesity
* High Blood Sugar
* Hypertension (High Blood Pressure)
* High Triglycerides
* Low H D L-Cholestero
Metabolic Syndrom Diagnostic Criteria
MetS Diagnstic Criteria:
* MetS is diagnosed when a patient has three of the following conditions:
* High blood pressure (≥ 130/85 mm Hg, or receiving medication)
* High blood glucose levels (≥ 5.6 mmol/L, or receiving medication)
* High triglycerides (≥ 1.7 mmol/L, or receiving medication)
* Low HDL-Cholesterol (< 1.0 mmol/L in men or < 1.3 mmol/L in women)
* Large waist circumference (≥ 102 cm in men, 88 cm in women; ranges vary according to ethnicity)
Diabetes
Diabetes = Elevated blood glucose (high blood sugar) due to insulin dysfunction.
Insulin = Hormone released by the pancreas to regulate blood glucose.
- Function: Signals cells to absorb glucose for storage or energy, lowering blood sugar to normal levels.
Causes of Diabetes:
- Insufficient insulin production.
- Cellular resistance to insulin, preventing effective glucose uptake.
Chronic high blood glucose can damage eyes, heart, nerves, blood vessels, and kidneys.
Diabetes in Indigenous Communities
Health Disparities: Indigenous communities in Canada face higher rates of diabetes compared to non-Indigenous populations due to complex factors.
Contributing Factors:
- Historical and ongoing colonial policies have affected access to healthcare and resources.
- Limited access to healthy, nutritious, and affordable food.
- Strong genetic predisposition for type 2 diabetes.
Health Access Challenges:
- Limited access to healthcare services like pharma care, ultrasounds, and palliative care, especially in remote communities.
- Lack of comfort or trust in larger urban healthcare settings.
Colonization led to a transition from physically active lifestyle revolving around hunting, fishing, other food gathering activities, and reliance on a nutritionally dense diet of traditional foods, to a more
sedentary lifestyle and reliance on less nutritious foods
Type 1 and Type 2 Diabetes
Healthy Insulin Function
- β-cells in the pancreas secrete insulin.
Insulin binds to cell receptors, signaling glucose uptake from the bloodstream.
Type 1 Diabetes
- Cause: Autoimmune disorder destroys β-cells in the pancreas, halting insulin production.
- Result: No insulin is produced, preventing cells from taking up glucose.
- Symptoms: More severe, as no insulin is available for glucose regulation.
Type 2 Diabetes
- Cause: Combination of insulin resistance (cells fail to respond to insulin) and non-functional β-cells.
- Result: Reduced glucose uptake despite insulin presence.
- Symptoms: Milder in early stages since some insulin is still secreted and normal functions occur, but glucose regulation is impaired.
Development of Insulin Resistance
Healthy Insulin Function
- β-cells in the pancreas release insulin in response to an increase in blood glucose levels.
- Insulin signals cells to take up glucose from the bloodstream.
Excessive Glucose Intake
- High food intake causes blood glucose levels to rise, prompting the pancreas to release larger amounts of insulin to help cells absorb excess glucose.
Continued Glucose Intake
- Persistent overconsumption leads to insulin receptor changes, reducing insulin binding and glucose uptake by cells.
- Start of insulin resistance: Cells become less responsive to insulin.
Insulin Resistance
- Resistance occurs in tissues like the liver, fat cells, and muscle, which become less responsive to insulin.
- Result: Higher blood glucose levels (hyperglycemia) due to reduced glucose uptake.
β-cell Damage
- To compensate for insulin resistance, the pancreas produces more insulin.
-Over time, the β-cells become overtaxed and may be damaged, losing the ability to produce enough insulin.
- Outcome: Blood glucose regulation becomes impaired, leading to hyperglycemia, especially in late-stage type 2 diabetes.
Symptoms and Diagnosis of Type 2 Diabetes
Common Symptoms of Type 2 Diabetes
1. Polyuria – Frequent urination due to excess glucose in the blood being filtered through the kidneys, which draws more water with it.
2. Polydipsia – Excessive thirst as the body tries to compensate for fluid loss from frequent urination.
3. Polyphagia – Excessive hunger, as the body’s cells are not receiving enough glucose for energy despite high blood glucose levels.
Testing:
- Blood tests
- Indicators are high fasting blood glucose and high hemoglobin A1C
Managing Type 2 Diabetes
- Lifestyle Changes First: Increased exercise and healthy eating may help manage or avoid type 2 diabetes, especially in early diagnosis or prediabetic cases.
- Role of Exercise and Diet: Regular exercise and reducing caloric intake can prevent or manage diabetes in many patients.
- When Medications are Needed: If lifestyle changes aren’t enough (e.g., due to genetic factors), medications are prescribed.
- Personalized Plans: Tailored solutions like dietary consultations and practical lifestyle adjustments (e.g., walking daily) help patients stick to their treatment.
Metformin
Metformin (Glucophage) is the first-line medication for type 2 diabetes, especially if a patient is
overweight. Its main function is to activate signaling pathways that play important roles in both sugar
and fat metabolism. Metformin directly inhibits glucose synthesis in the liver.
Metformin treatment has been shown to:
* Increase insulin sensitivity
* Decrease absorption of glucose from the diet
* Promote catabolism of glucose in cells
Affects of Severe Type 2 Diabetes
Severe type 2 diabetes may affect the body.
Eyes
Vision loss due to retinal damage.
Heart
Development of cardiovascular disease and heart disease, and heightened risk of heart attacks and
strokes.
Pancreas
Failure of the pancreas to create insulin. Additional pharmaceuticals may be prescribed to counteract
this, including replacement insulin therapy.
Kidneys
Elevated glucose levels in the blood cause the kidney to struggle to filter it, and may lead to damage to
both kidney blood vessels and normal function.
Feet
Development of diabetic peripheral neuropathy causes foot problems, since the loss of feeling in the
feet leads to tissue damage and ulcers being unnoticed. Severe cases may lead to amputation.
Diabetes Risk Factors
Age
Type 1 diabetes is commonly seen in any age but typically young children.
Type 2 diabetes is more common in those 45+ years old. However, this is dropping with obesity
epidemic in children.
Lifestyle
There is no known impact of lifestyle on type 1 diabetes and no known ways to prevent it. Type 2
diabetes, however, is strongly linked to poor diet and low physical activity. Hence, risk for type 2
diabetes can be lowered by eating healthy and increasing daily exercise.
Family History
Having a family member with type 1 or type 2 diabetes increases risk of being diagnosed with each
respectively
Atherosclerosis
Definition: A type of cardiovascular disease involving thickening of arteries due to inflammation and plaque (fatty deposits) buildup.
Early Development: Atherosclerosis often starts early in life, making it difficult to gather accurate incidence and prevalence data.
Serious Consequences: Severe atherosclerosis can lead to fatal conditions like heart attacks and strokes, as it blocks or reduces blood flow to critical organs.
Formation and Progression of Atherosclerosis:
Injury:
Endothelial cells lining blood vessels get injured due to factors like smoking, hypertension, high blood pressure, and viruses.
Injury leads to the accumulation of LDL (low-density lipoprotein) at the damaged sites.
Infiltration:
LDL accumulation causes further inflammation, attracting platelets and immune cells (such as macrophages).
These immune cells infiltrate the vessel wall and contribute to the inflammatory process.
Lipid Buildup:
Immune cells attempt to clear the accumulated lipids but end up engulfing them, leading to cell death (apoptosis).
This contributes to more inflammation and the formation of the first visible signs of atherosclerotic plaque.
Smooth muscle cells in the blood vessel wall also move into the region and engulf lipids.
Complete Plaque:
The plaque continues to grow as inflammation, infiltration, and lipid buildup intensify.
Collagen and immune cells accumulate, increasing the size of the plaque.
The plaque narrows or blocks the blood vessel, weakening the vessel wall.
If the plaque ruptures, a piece may dislodge, travel through the bloodstream, and cause an embolism (blockage elsewhere).
Risk of Atherosclerosis
Diabetes
Weight
Smoking
Pre-existing Heart Disease
Common Sites of Atherosclerosis:
Carotid Arteries:
These arteries supply blood to the brain. Atherosclerosis in the carotid arteries can lead to plaque buildup, causing narrowing (stenosis) and turbulence in blood flow. This can increase the risk of blood clots forming and potentially causing a stroke.
Carotid Doppler Ultrasound is used to detect narrowing and plaque buildup. It visualizes blood flow through the artery and helps identify blockages or turbulence.
Coronary Arteries:
Atherosclerosis in these arteries can cause heart disease, including heart attacks. The condition can block or narrow blood flow to the heart muscle, leading to ischemia (lack of oxygen).
Ilio-Femoral Arteries:
These arteries supply blood to the lower limbs. Atherosclerosis can lead to peripheral artery disease, causing pain, difficulty walking, and increasing the risk of gangrene.
Atherosclerosis Testing
Echocardiogram (Cardiac Ultrasound) Overview:
An echocardiogram uses high-frequency sound waves (ultrasound) to create images of the heart. This test evaluates heart chambers, valves, and major blood vessels like the aorta.
In Mr. Smith’s case, it was used to check for blood clots in the heart that might have contributed to his stroke, but no clots were found.
Carotid Doppler Ultrasound:
A Doppler ultrasound of the carotid arteries assesses blood flow, and turbulence can be detected with color-coded imaging. The presence of a plaque or atheroma (fatty deposit) within the artery is also identified.
In Mr. Smith’s case, the Doppler revealed significant narrowing and blockage in his left internal carotid artery due to atheroma, which likely led to the stroke.
Carotid Endarterectomy (CEA) Overview:
Purpose of the Procedure:
Carotid endarterectomy is a common surgery used to treat patients with a narrowed carotid artery due to plaque buildup, a major risk factor for stroke. The goal is to remove the plaque and restore normal blood flow to the brain.
Indications for Surgery:
Surgery is typically considered when the carotid artery is severely narrowed and the plaque is unstable (ulcerated) or when medication alone isn’t sufficient to manage the condition. A high degree of narrowing and the presence of “ugly” plaque (plaque with craters that can cause blood clots) are common indications.
Procedure:
The surgery is performed under general anesthesia.
A small incision is made on the neck, and the carotid artery is carefully dissected out.
Temporary clamps are placed on the carotid artery to stop blood flow, allowing the surgeon to open the artery, remove the plaque, and then sew the artery back together using fine sutures.
Blood flow to the brain is restored immediately after the surgery.
Recovery:
Patients typically stay in the hospital overnight or for an additional day depending on their condition.
Most patients recover within one to two weeks, with the majority of recovery taking place at home.
Comprehensive Care Team:
The surgery involves a team of specialists, including neurosurgeons and vascular surgeons, as well as a neural ICU team to manage post-operative care, such as blood pressure and pain management.
