Pathology

• The Four Gs


  • Glucogenesis
  • Glycogenesis
  • Glycolysis
  • Glycogenolysis
• Glucogenesis


  Creation of glucose from sources other than carbs (proteins, glycerol, lactate)
• Glycogenesis


  Creation of glycogen (easily turned into glucose)
• Glycolysis


  The breakdown of glucose with an individual cell to release ATP
• Glycogenolysis


  Breakdown of glycogen to glucose
• Diabetes


  Abnormality in blood glucose regulation and nutrient storage related to an absolute deficiency in insulin or resistance to actions of insulin
• Functions of the pancreas

  • Exocrine (digestive enzymes and bicarbonate in duodenum)
  • Endocrine (insulin and glucagon for blood glucose levels)
• Cells in the pancreas

  • F cell (secretes pancreatic polypeptide)
  • Beta cell (secretes insulin)
  • Alpha cell (secretes glucagon)
  • Delta cell (secretes somatostatin)
• Insulin


  Drives glucose into cell, produced in beta cells, causes uptake of glucose into cells and its storage as glycogen, fat, protein, stimulates glucose breakdown for energy within a cell, promotes storage and breakdown, prevents fat breakdown and glycogen breakdown
• Glucagon


  Made in alpha cells, stimulates the release of glucose into your blood when fasting, liver is prime storage depot, increases glycogenesis (breakdown of glycogen to glucose)
• In starvation


  The goal is to protect the brain and the heart, glucagon mobilizes glucose stores from the liver so it can be sent to brain and heart, also increases the transport of amino acids to liver to stimulate gluconeogenesis
• Counter Regulatory Hormones


  • Catecholamine
  • Growth hormone
  • Glucocorticoids
• Counter Regulatory Hormones counteract storage of insulin to decrease depletion of serum to glucose during fasting, exercise, illness (fever), and stress
• Types of Diabetes


  • Type 1
  • Type 2
  • Gestational
• Type 1 Diabetes


  Loss of production of insulin, autoimmune (Type 1a) or idiopathic (Type 1b)
• Type 2 Diabetes


  Insulin resistance by body cells, increase in production to compensate for peripheral tissue resistance and mechanism fails, burn out of pancreas
• Risk factors for Type 2 Diabetes

  • Age
  • Obesity
  • Family history
• Metabolic abnormalities in Type 2 Diabetes

  • Insulin resistance
  • Increased glucose production by liver
  • Deranged secretion of insulin by pancreatic beta cells
• Obesity and physical inactivity are the two paramount factors in the development of Type 2 Diabetes
• Features of Metabolic Syndrome (Type 2 Diabetes)


  • Abdominal sensitivity
  • Hyperglycemia
  • Hypertension
  • Hyperlipidemia
• Role of Adipose Tissue in Type 2 Diabetes

  Increase in free fatty acids, excess free fatty acids cause pancreatic beta cell dysfunction (lipotoxicity), free fatty acids inhibit glucose uptake and glycogen storage, accumulation of free fatty acids decreases insulin sensitivity, leads to increased hepatic glucose production and hyperglycemia
• Gestational Diabetes


  Glucose intolerance that begins during pregnancy, placenta produces hormones that help shift nutrients from mother to fetus and prevent low blood glucose of mother, placenta hormones resist insulin action and lead to increase in glucose levels, in attempt to decrease glucose levels, mother's body increases insulin by 3x, if pancreas can't produce enough insulin = GD
• Risk factors for Gestational Diabetes

  • Glycosuria
  • Strong family history of type 2
  • Obesity
  • Prior history
  • Previous delivery of large infant
• Screening for Gestational Diabetes: risk assessment at first visit, if increased risk - glucose testing, if lower risk - oral tolerance test at 24-28 weeks
• Fetal Abnormalities in Gestational Diabetes

  • Macrosomia
  • Hypoglycemia
  • Hypocalcaemia
  • Polycythemia
  • Hyperbilirubinemia
• Treatment of Gestational Diabetes

  • Close observation (maternal fasting and post meal monitoring, fetal growth measurements)
  • Diet alterations
  • Insulin therapy if diet not effective
• 50% of women with Gestational Diabetes develop Type 2 Diabetes in 5-10 years after delivery
• Manifestations of Diabetes


  • Hyperglycemia
  • Polyphagia (excess hunger)
  • Polydipsia (excess thirst)
  • Polyuria (excess urination)
• Rationale for Poly Symptoms

  Lots of glucose that can't be moved into cells, glucose stays in blood and is excreted by kidneys, ineffective use of glucose leads to weight loss and increased appetite, increased blood glucose makes blood hypertonic that creates osmotic pressure that sucks water into vascular space, increased urination and thirst
• General Clinical Manifestations of Diabetes

  • Weight loss
  • Blurred vision
  • Paresthesia (decreased sensation)
  • Fatigue/weakness
  • Chronic infections
• Type 2 Diabetes Manifestations

  Gradual onset, 90 years undetected, osmotic fluid/electrolyte loss from hyperglycemia, nonspecific symptoms (fatigue, recurrent infections, recurrent yeast infections, prolonged wound healing, vision changes, painful peripheral neuropathy on feet)
• Diagnostics for Diabetes


  • Fasting plasma glucose
  • Casual blood glucose test
  • Oral glucose tolerance test
  • Capillary blood glucose monitoring
  • Glycosylated hemoglobin
• The desired outcome of glycemic control in both type 1 and type 2 diabetes is normal blood glucose and preventing complications
• Diabetes Management


  • Diet
  • Exercise
  • Antidiabetic agents (oral for type 2, injections for type 1 and advanced type 2)
• Types of Insulin


  • Fast acting
  • Intermediate acting
  • Long acting
• Acute Complications of Diabetes

  • Diabetic ketoacidosis
  • Hyperosmolar hyperglycemic state
  • Hypoglycemia
• Diabetic Ketoacidosis


  Characterized by hyperglycemia, ketosis, metabolic acidosis, primarily in type 1 but can occur in type 2 with severe stress, occurs with omission or inadequate use of insulin, lack of insulin leads to rapid breakdown of energy stores from muscle and fat, in ketosis, increased counter regulatory hormones are released leading to hyperglycemia
• Diagnosis of Diabetic Ketoacidosis

  • Hyperglycemia (>13.8 mmol/L)
  • Decreased serum bicarbonate
  • Decreased arterial pH
  • Positive ketones (urine and blood)
• Manifestations of Diabetic Ketoacidosis

  • Fruity breath odor
  • Increased heart rate
  • Hypotension and bradycardia
  • Increased rate and depth of respiration
• Treatments for Diabetic Ketoacidosis


  • Improve circulatory volume and tissue perfusion (IV fluids)
  • Decrease blood glucose (insulin infusion)
  • Correct acidosis
  • Correct electrolyte imbalance (potassium in fluid)