كيمياء سريرية 2 - تنظيم سكر الدم

Clinical Biochemistry 2 - Metabolic Integration and Blood Sugar Regulation

• Introduction: The human body manages thousands of chemical reactions to maintain energy supply for all cells in various conditions (fasting, starvation, obesity, and metabolic diseases like diabetes).
• Metabolic Adaption: Metabolic adaptation adjusts to different conditions.
• Daily Fuel Requirements: An average adult (70 kg) needs 2400-2000 kcal daily, divided amongst carbohydrates (40-60%), fats (30-40% - primarily TAG), and proteins (10-15%).
• Metabolic Reserves: The body creates reserves of carbohydrates (glycogen in liver and muscles) and fats (TAG in adipose tissue) for use between meals.
• Metabolic Imbalance: Imbalances in metabolic pathways, hormonal imbalances, and increased metabolic demands (pregnancy, lactation, insufficient food intake), cause disruptions in metabolic regulation, resulting in conditions like type 1 and 2 diabetes, where insulin production or sensitivity is disrupted.

Metabolic Integration and Blood Sugar Regulation

• Introduction: This section explores how different metabolic pathways are connected and regulated, particularly focusing on blood sugar regulation.
• Metabolic Interconversions: The flowchart illustrates how carbohydrates, fats, and proteins interconvert to provide energy and building blocks for other molecules.
• Metabolic Pathways Summary: The provided table shows major metabolic pathways (glycolysis, glycogenolysis, gluconeogenesis, etc.) and their corresponding inputs, outputs, and regulatory mechanisms.

Additional Notes

• Fasting State:
  • Glucose is crucial for the central nervous system, which cannot use fatty acids or ketone bodies initially.
  • Other tissues can use alternative fuels like fatty acids and ketone bodies if glycogen stores are depleted.
• Hormonal Regulation:
  • Insulin and glucagon are crucial hormones in regulating metabolic processes and providing appropriate fuel to different tissues.
• Metabolic Imbalance and Its Causes: A table lists factors causing metabolic imbalance in the body.
• Metabolic Interconversions summary: The table shows the interconversions between carbohydrates, fats & proteins with a focus on the necessary fuel for various tissues.

Metabolic Integration and Blood Sugar Regulation

• Metabolic Fuels and Interconversions:
• During the post-absorptive state, glycogenolysis and gluconeogenesis provide glucose as the primary fuel.
• Skeletal muscle utilizes fats as a primary fuel during fasting.
• Liver plays a critical role in managing glucose levels during fasting and utilizing fatty acids for energy and synthesizing new glucose molecules.

Metabolic Fuels and Interconversions

• Glycemic Control and Hormonal Adjustments: The role of hormones (insulin, glucagon, and adrenaline) is crucial in maintaining glycemic control.
• Metabolic Interplay:
  • Many pathways have common intermediate products (e.g., pyruvate, acetyl-CoA), facilitating coordination of different metabolic pathways.
• Intermediary Metabolism Summary: A table that summarizes the metabolic pathways, substrates (inputs), products, and regulatory points, along with their interaction and coordination.

Body Fuels During Fasting and Feeding

• Post-Absorptive State (Feed Mode):
• Excess glucose is converted into glycogen in the liver and muscle to be stored.
• Some glucose is used for fat synthesis (TAG) in the liver and exported as VLDL.
• Glucose uptake by muscle and adipose tissue is regulated by insulin.
• Liver glucose uptake is not insulin-dependent.
• Post-Absorptive State (Fasting):
• Tissues including brain and red blood cells require continuous glucose supply
• Muscle and heart tissues prefer the oxidation of fatty acids over glucose.

Metabolic Fuels During Fasting

• The liver and adipose tissues release glucose and fatty acids, respectively, to maintain blood glucose levels.
• Fatty acids are used as primary fuel by muscle and heart, sparing glucose for the brain.

Diabetic Ketoacidosis: DKA

• Pathogenesis of DKA: The flowchart charts the pathological mechanism of DKA.
• Symptoms and Signs of DKA: A table lists specific symptoms and signs of DKA.
• Investigational Approaches: A table includes investigations for diagnosing and monitoring DKA.

Nonketotic Hyperglycemic Hyperosmolar Coma: HONK

• Pathogenesis: The flowchart charts the pathological mechanism of HONK.
• Symptoms and Signs: A table lists specific symptoms and signs of HONK.
• Diagnostic Investigation: A table including investigations for diagnosing and monitoring HONK.

Mechanisms of Endocrine Regulation

• Hormones, Their Role and Triggering Mechanisms: The table includes a summary of the hormonal mechanisms of glycemic control.
• Hormonal Modulation (by cAMP): Regulation of metabolic pathways by increasing or decreasing cAMP levels, which is induced by different hormones (glucagon, adrenaline).

Diagnosing Diabetes

• Diagnostic Criteria: Methods used to diagnose or monitor a patient with diabetes, covering both fasting plasma glucose and oral glucose tolerance tests.