الكيمياء السريرية 2 - تنظيم الأيض

Clinical Biochemistry 2 - Metabolic Integration and Glucose Regulation

• Overview: The human body meticulously regulates thousands of chemical reactions to provide energy to each cell under various circumstances, like fasting, feasting, obesity and metabolic disorders like diabetes.

• Daily Caloric Needs: A 70kg adult needs 2400-2000 calories daily, met from carbohydrates (40-60%), fats (30-40%), proteins (10-15%), and alcohol if consumed.

• Metabolic Reserves: The body stores carbohydrates (glycogen in liver and muscles) and fats (TAG). These reserves are used between meals.

• Metabolic Imbalanced: Imbalances in metabolic or hormonal regulation can occur for several reasons, including pregnancy, breastfeeding, inadequate calorie intake, Type 1 diabetes (impaired insulin production), and Type 2 diabetes (impaired tissue response to insulin).

Metabolic Integration and Glucose Regulation in Fasting

• Glucose Necessity: The central nervous system needs a constant supply of glucose for fuel in all conditions. It does not utilize fatty acids or ketone bodies initially.

• Other Tissues: Other tissues can use alternative fuels like fatty acids and ketone bodies.

• Glycogen Depletion: When liver glycogen stores are depleted, glucose is derived from glycerol from fat breakdown.

• Amino Acids: Amino acids from protein breakdown can generate glucose for tissues needing it.

Metabolic Transitions and Interconversions

• Carbohydrates: Used for energy and glycogen synthesis in the liver and muscles. Excess is converted to fat (TAG) in adipose tissue and liver.

• Fats (TAG): Synthesized in adipose tissue and liver. Most importantly, pyruvate converts to Acetyl CoA, which creates long-chain fatty acids.

• Amino acids: Serve as substrates for glucose production (gluconeogenesis) and form non-essential amino acids from glucose intermediates.

Metabolic Integration Regulation and Hormones

• Insulin: Promotes carbohydrate storage and utilization.

• Glucagon & Adrenaline: Stimulate glycogen breakdown and fuel mobilization (primarily during fasting).

Metabolic Integration During Feeding

• Glucose Utilization: Glucose is the major fuel for most tissues, stimulated by rising blood glucose, triggering insulin secretion.

• Liver & Adipose: Liver synthesizes glycogen and TAG, exporting VLDL. Fat is stored in adipose tissue.

• Tissue Uptake: Muscle and adipose tissue uptake glucose through insulin regulation.

• Liver: Liver absorbs glucose independently of insulin.

Metabolic Integration During Fasting

• Depletion: As blood glucose levels fall, glucagon and adrenaline promote glycogen breakdown in the liver to release glucose maintaining blood levels.

• Adipose Tissue: Increased fatty acid release for alternative fuel use in other tissues.

• Muscle & Liver: The liver and muscles utilize fatty acids as main energy source.

• Ketone Bodies: The liver produces ketone bodies when glucose reserves are low.

Comparing Type 1 vs Type 2 Diabetes

• Type 1: Generally develops in childhood or early adulthood. Characterized by an autoimmune destruction of pancreatic beta cells, leading to absolute insulin deficiency.

• Type 2: Usually appears in middle age. It's characterized by defects in insulin secretion and/or resistance to insulin action.

• Consequences: Both types result in elevated blood glucose (hyperglycemia), potentially leading to long-term complications (retinopathy, nephropathy) and other severe conditions.

Diagnostic Criteria for Diabetes Mellitus

• Fasting Plasma Glucose: A fasting plasma glucose level of 7.0 mmol/L (126 mg/dL) or higher is diagnostic for diabetes.

• Oral Glucose Tolerance Test: Values exceeding 11.1 mmol/L (200 mg/dL) two hours after ingesting 75 grams of glucose indicate diabetes.

Other Metabolic Disorders and Conditions

The document describes Neonatal Diabetes, Maturity-onset Diabetes of the Young, gestational diabetes, ketoacidosis (DKA and HONK), lactic acidosis, and hypoglycemia.

Additional Notes

• Hormonal Regulation: Insulin, glucagon, and catecholamines are crucial for metabolic control.

• Glycemic Control: The control for HbA1c is a major indicator of long-term glucose control, monitored frequently to prevent complications.

• Hypoglycemia: Symptoms and causes of hypoglycemia, emphasizing the role of insulin, hormones and other factors in its manifestation.

يتناول هذا الاختبار تنظيم الأيض وتوازن السكر في الجسم. سيتعلم المشاركون كيفية إدارة احتياجات السعرات الحرارية والاحتياطيات الأيضية في ظروف مختلفة مثل الصيام والسمنة. كما سيسلط الضوء على الاختلالات التي يمكن أن تنشأ نتيجة لمشاكل تنظيم الأيض.