Ch. 25

KETOACIDOSIS

- I'm starving!!! - fat is broken down into ketone bodies to feed the body (and especially the brain) - Brain function is reliant solely on glucose; therefore, blood glucose levels must not decline to very low levels. - Ketone accumulation in the bloodstream is known as ketosis or ketoacidosis. - (=metabolic acidosis) - fruity breath smell

Glycogenolysis

- is the process of glycogen breakdown. During periods of starvation, the body is capable of producing glucose through the breakdown of glycogen (called glycogenolysis) and gluconeogenesis.

gluconeogenesis

During times when fasting is prolonged or starvation occurs, glycogen stores in the liver will be depleted. The liver then can synthesize glucose by another process: gluconeogenesis. In gluconeogenesis, amino acids and fats are converted into glucose.

Gestational DM Increases Risk for T2DM

Women with GDM are at high risk for GDM in future pregnancies. In some women, the stress of pregnancy provokes the development of a permanent condition of diabetes. Studies show that about 50% of women who get gestational diabetes will develop type 2 diabetes within the first 5 years after delivery.

Long-Term Complications of DM

- Arteriosclerosis - Peripheral angiopathy (lack of circulation) - Diabetic retinopathy - Diabetic neuropathy - Autonomic neuropathy - Diabetic nephropathy - Poor wound healing - Immunosuppression

Long-Term Complications of DM

- Arteriosclerosis--> myocardial infarction - Peripheral angiopathy (lack of circulation)--> limb ischemia - Diabetic retinopathy--> blindness - Diabetic neuropathy--> lack of sensation in lower limbs, burning, tingling - Autonomic neuropathy--> lack of sympathetic nervous system stimulation in hypoglycemia - Diabetic nephropathy--> kidney failure - Poor wound healing--> gangrene - Immunosuppression--> infection

Diabetes Mellitus (DM)

- DM is a disorder of carbohydrate metabolism. - It is characterized by high levels of blood glucose, resulting from the body's inability to produce or utilize insulin.

Diagnostic Criteria for DM

- Fasting blood glucose - Normal: 70 to 99 mg/dL - Prediabetes: 100 to 125 mg/dL - Diabetes: 126 mg/dL or higher - Two-hour plasma glucose during oral glucose tolerance test - Prediabetes: 140 to 199 mg/dL - Diabetes: 200 mg/dL or higher - Random plasma glucose - Diabetes: 200 mg/dL or higher - Hgb A1c glycated hemoglobin (used for diagnosis or tracking glucose control) - Prediabetes: 5.7% to 6.4% - Diabetes: 6.5% or higher

Why Does Amputation Occur in DM?

- Peripheral neuropathy: lack of sensation in lower extremities - Peripheral angiopathy: poor circulation in lower extremities --> ischemia of lower extremities - Wound in lower extremity can occur without patient sensing the skin breakdown - Immunosuppression--> increased infection susceptibility - Infection and ischemia of limb--> gangrene amputation

Ketonuria

A urine dipstick test or urinalysis will reveal glucosuria, which is indicative of uncontrolled diabetes. Also, ketones in the blood, which are filtered at the kidney, can appear in the urine. Urine that contains ketones is termed ketonuria.

Glucose ➔ Absorbed ➔ Used or Stored

After absorption into cells, glucose can either be used for energy production, be stored in the form of glycogen, or be converted into fat. All cells can store some glucose in the form of glycogen, but the liver and muscle cells can store the largest amounts.

Gestational DM Large Infant (Called Macrosomia)

Diabetic mother has hyperglycemia which stimulates insulin. The glucose passes through the placenta into the fetus. Maternal insulin is a large molecule and does not cross the placenta. The infant is stimulated to produce its own high insulin. Without treatment, in uncontrolled GDM, the constant high maternal blood glucose levels cause high fetal blood glucose levels. High maternal glucose levels are excessive and more than the fetus needs for normal growth; extra glucose is stored as fat in the fetus. The extra fat synthesized in the fetus often leads to large-for-gestational-age newborns. After birth, the newborn continues to produce insulin--> leading to neonatal hypoglycemia.

Glucosuria

During hyperglycemia of uncontrolled diabetes, blood filtered by the kidney contains a high level of blood glucose. At the nephrons of the kidney, glucose is reabsorbed back into the bloodstream to a certain threshold and the remaining unreabsorbed glucose remains within the tubule fluid to enter the urine. Glucose in the urine is termed glucosuria.

Starvation ➔ Liver Glycogen, Fat, and Muscle Breakdown

During periods of starvation, the liver is called upon to release its glucose storage (glycogen breakdown). Also, adipose tissue breakdown is utilized to yield fatty acids to manufacture glucose. Muscle mass may be called upon to release proteins--> amino acids to be used to manufacture glucose in the liver. Consequently, prolonged starvation causes depletion of fat stores and muscle mass.

Fluid Shifts in DKA

Excess water in bloodstream--> polyuria Excess glucose in blood--> glycosuria Hyperglycemia causes cell dehydration. At the kidney, a certain amount of glucose is reabsorbed into the bloodstream, up to a threshold; then glucosuria occurs.

Gestational DM (GDM)

GDM requires treatment to normalize maternal blood glucose levels in order to avoid complications in the infant. In the absence of treatment, GDM can cause fetal defects, premature delivery, hypoglycemia in the newborn, and large-for-gestational-age infants. Commonly, pregnant women are screened for GDM with an oral glucose tolerance test (OGTT) during the second trimester.

Electrolyte Disturbances in DKA

Hyperglycemia raises osmotic pressure of the bloodstream--> sucks in intracellular fluid into the bloodstream--> cellular dehydration and excess water in blood polydipsia Dilution hyponatremia Cellular K+ leaves intracellular compartment in presence of acidosis--> H+ enters intracellular compartment and shifts K+ into bloodstream--> false hyperkalemia

Physiological Maintenance of Glucose

Ideally, when blood glucose levels remain within the normal range, the rise and fall of blood insulin concentration is proportional to the rise and fall in blood glucose.

Exercise Increases Skeletal Muscle Glucose Uptake

Individuals with diabetes must remember that strenuous muscle activity will reduce blood glucose levels, which can lead to hypoglycemia. Exercise should be scheduled 1 to 2 hours after a meal or when insulin is not at peak levels. The individual should ingest carbohydrate snacks during sustained exercise and vigilantly monitor blood glucose.

Pathological Mechanism of T2DM

Insulin resistance is the major pathophysiological process that causes T2DM. The insensitivity of body cells to insulin causes the pancreas to attempt to compensate by secreting increasing amounts of insulin. Greater-than-normal amounts of pancreatic insulin are required to produce a normal biological response, causing the pancreas to overwork. Eventually, the pancreas becomes exhausted.

T2DM

Obesity is a major contributing factor to the development of T2DM . Fat cells are particularly resistant to insulin; the greater the adiposity of an individual, the greater the insulin resistance. The risk of developing T2DM increases with age, obesity, and lack of physical activity.

Metabolic Syndrome

Persons with metabolic syndrome have insulin resistance, hypertension, dyslipidemia, hyperinsulinism, centralized or "apple-shaped" obesity, glucose intolerance, and a predisposition to T2DM. Metabolic syndrome increases the risk of coronary artery disease and other diseases related to arteriosclerosis, such as stroke and peripheral vascular disease. Obesity (apple-shaped) Hypertension High triglycerides Low HDL Insulin resistance

End Result of All Theories of Pathophysiological Mechanism: Endothelial Injury

Regardless of the etiologic mechanism, chronic hyperglycemia in diabetes is known to cause endothelial injury which, in turn, activates inflammation. Inflammation brings WBCs, inflammatory mediators, and platelets to the site of endothelial injury. Lipid and macrophage deposition within the injured area causes the eventual formation of foam cells, precursors to atherosclerotic plaque. Simultaneously, in response to injury, endothelial membranes secrete endothelin. Endothelin inhibits arterial vasodilation and promotes vascular smooth muscle proliferation. This narrows the diameters of arterial vessels. Hyperglycemic damage to the smallest arterial blood vessels occurs initially, with arterial vessels of the retina, delicate nutrient arterial vessels of the neurons, and arterial vessels surrounding the nephrons primarily demonstrating this endothelial damage.

Why Is DM Harmful? How Does DM Cause Cellular Damage?

Several theories try to answer those questions. Basically, glucose harms the endothelium.

HgbA1c (A1c)

The glycated hemoglobin (HbA1c) test (also called A1c) can be used to diagnose diabetes and assess blood glucose control over the preceding 3 months. A HbA1c value of greater than 6.5% is diagnostic of diabetes, and a value between 5.7% and 6.4% is considered prediabetes. The ADA allows for glycated hemoglobin testing paired with fasting plasma glucose on the same day. If values of both are in the diabetic range, the diagnosis is confirmed.

Low Glycemic Index Diet

The glycemic index measures how a carbohydrate-containing food raises blood glucose. Carbohydrate-containing foods with a low glycemic index include dried beans and legumes, most vegetables, most fruit, and whole grain breads and cereals. As a general rule, the more processed a food, the higher the glycemic index.

Other Hormones That Increase Insulin

The other hormones that either directly increase insulin secretion or enhance the glucose stimulus for insulin secretion include growth hormone, cortisol epinephrine progesterone estrogen

Diabetic Ketoacidosis (DKA)

This is a condition that develops in those with no insulin reserves, such as those with uncontrolled type 1 diabetes. Individuals with type 1 diabetes often present with DKA when first diagnosed; DKA is a critical condition requiring immediate treatment. When there is no glucose entering cells because of either lack of insulin or resistance to insulin, cells go into starvation mode.

Autonomic Neuropathy

This possible side effect of diabetes can cause dysfunction of the compensatory sympathetic response to low blood glucose. The patient fails to experience the warning signs of hypoglycemia, such as tachycardia and nervousness, and can endure the condition, unknowingly, until suffering loss of consciousness.

Hypoglycemia

When blood glucose levels fall to hypoglycemic levels (lower than 70 mg/dL), the hypothalamic region of the brain and portal vein of the liver sense the drop in glucose. These glycemic sensors initiate a compensatory response mainly involving the adrenal gland, pancreas, and liver. Epinephrine and glucagon are released, causing activation of the sympathetic nervous system and rise in blood glucose. Activation of the sympathetic nervous system is responsible for most of the initial signs and symptoms of hypoglycemia, which include: Sweating Hunger Dizziness Nervousness Tremulousness Irritability Headache Heart palpitations Confusion Disorientation Inability to concentrate Seizures Loss of consciousness

Insulin Reaction

causes - excessive insulin - delayed meal - insufficient food - excessive exercise S/S - rapid onset - hunger - trembling and paleness - feeling of faintness - cold sweat - headache - anxiety - irritability - impaired vision - hypoglycemia - confusion - seizures - loss of consciousness Intervention - sugar, candy, orange juice, soda. Emergency situation

Diabetic Coma

causes - undiagnosed diabetes - skipped insulin dose - excessive food - infection or stress S/S - slow onset - thirst - N/V - drowsiness - lethargy - flushed appearance - dry skin - fruity breath odor - dehydration - heavy respirations - dilated fixed pupils - hyperglycemia - ketoacidosis - loss of consciousness - coma Intervention - give insulin, fluids, salt. Emergency situation

Glycogenesis

is the process of glycogen formation.

HIGH BLOOD SUGAR

leads to frequent infections and dental caries (bacteria loves sugar!) hypertonic blood leads to thirst (polydypsia) and polyuria damage to blood vessels leading to peripheral vascular disease, coronary artery disease, and stroke especially retinopathy, nephropathy, and/or neuropathy cells are still starving....polyphagia

Complications of DM

short term: Hyperglycemia Hypoglycemia DKA in T1DM Hyperosmolar hyperglycemic syndrome (HHS) in T2DM Long term: Retinopathy Nephropathy Arteriosclerosis Peripheral neuropathy Intractable infections Amputations

Steps

step 1: carbs step 2: pancreas step 3: insulin (puts glucose into the cells).

What Happens in Prolonged Fasting?

step 1: insufficient intake of glucose step 2: hypoglycemia step 3: body cells sense starvation step 4: liver begins to break down glycogen into glucose. Glucose from liver increases in bloodstream. step 5: when liver glycogen is exhausted, fat breakdown begins. step 6: when fat breakdown is exhausted, muscle breakdown occurs. All to raise blood glucose levels.