Midterm Carbohydrate Diseases PDF

CLINICAL CHEMISTRY John Leo C. Dayrit, RMT  CARBOHYDRATES These are hydrates of aldehyde or ketone derivates based on the location of the CO functional group. Classification of carbohydrates: Monosaccharides, Disaccharides, Oligosaccharide...

CLINICAL CHEMISTRY John Leo C. Dayrit, RMT  CARBOHYDRATES These are hydrates of aldehyde or ketone derivates based on the location of the CO functional group. Classification of carbohydrates: Monosaccharides, Disaccharides, Oligosaccharides, Polysaccharides Glycol aldehyde is the simpliest carbohydrate (CHO) Glucose is the only carbohydrate to be directly used for energy or stored as glycogen. Glucose does not accumulate in the muscle. It does not enter the muscle cell freely, and when it enters the cell with the help of insulin, it is quicky metabolized. Glucose metabolism generates pyruvic acid, lactic acid and acetylcoenzyme A as intermediate products. Glycoaldehyde is the simplest CHO Reducing and Non-reducing sugars: Glucose,Maltose,Fructose,Lactose and Galactose The presence of a double bond and a negative charge in the anion makes glucose an active reducing substance Sucrose is the most common non-reducing sugar Nonreducing sugar do not contain an active ketone or aldehyde group PANCREAS It is both an endocrine and exocrine organ in the control of carbohydrate metabolism. Endocrine gland - as it secretes the Exocrine gland- it produces and hormones’ insulin, glucagon and secretes an amylase responsible for somatostatin from different cells residing the breakdown of ingested complex in the islets of langerhans in the pancreas carbohydrates INSULIN It is the primary hormone responsible for entry of glucose into the cell. It is synthesized by the Beta cells of the islets of Langerhans in the pancreas Normally released when the glucose levels are high It is the only hormone that decreases glucose levels - hypoglycemic agent It is stored from sources such as liver, fat and muscle It has a reciprocal relationship with glucagon Promotes glycogenesis, lipogenesis and glycolysis; decreases glycogenolysis It enhances membrane permeability to cells in the liver, muscle and adipose tissue. Serum insulin measurements may be falsely low in the presence of hemolysis. GLUCAGON It is the primary hormone responsible for increasing glucose - hyperglycemic agent It is synthesized by the Alpha cells of the islets of Langerhans It is released during stress and fasting states It enhances catabolic function during fasting periods; promotes glycogenesis Fasting plasma glucagon concentrations is normally 25-50 pg/mL Glycogenesis- is the process of converting glucose into glycogen for storage, primarily in the liver and muscle cells. It occurs when there is an excess of glucose in the bloodstream, such as after eating. Glucogenolysis- this is the process of breaking down glycogen (a stored form of glucose) into glucose. It primarily occurs in the liver and muscle cells when the body needs glucose for energy, such as during fasting or intense exercise Gluconeogenesis- this is the process of synthesizing glucose from non-carbohydrate precursors, such as amino acids, lactate, and glycerol Other hormones that increase glucose concentration 1. Cortisol and corticosteroids (Glucocorticoids) secreted by the cells of the zona fasciculata and zona reticularis of the adrenal cortex they decrease intestinal entry of glucose into the cell they promote gluconeogenesis and lipolysis 2. Catecholamines These are released from the chromaffin cells of the adrenal medulla They inhibit insulin secretion and promotes glycogenolysis and lipolysis 3. Growth Hormone (Somatotropin) aka GH It is secreted by the anterior pituitary gland They decrease entry of glucose into the cell It promotes glycogenolysis and glycolysis 4. Thyroid hormones It promotes glycogenolysis, gluconeogenesis and intestinal absorption of glucose  5.Adrenocorticotropic hormone (ACTH) It stimulates release of cortisol from the adrenal cortex It promotes glycogenolysis and gluconeogenis 6.Somatostatin It is produced by the delta cells of the islets of langerhans and inhibits the action of insulin CLINICAL CONDITIONS RELATED TO CHO METABOLISM Hyperglycemia It is characterized by an increase in blood glucose concentration. It is toxic to beta-cell function and impairs insulin secretion. Causes: Stress, severe infection, dehydration, pregnancy, pancreatectomy, hemochromatosis, and insulin deficiency or abnormal insulin receptor A fasting plasma glucose of ≥ 126 mg/dL is indicative of hyperglycemia Hypoglycemia It results from an imbalance between glucose utilization and production. Involves decreased glucose levels and can have many causes. The warning signs and symptoms of hypoglycemia are related to the central nervous system. A diagnosis of hypoglycemia should not be made unless patient meets the criteria of Whipple's Triad: low blood glucose concentration, typical symptoms are seen, and symptoms alleviated by glucose administration Interpretation of plasma glucose values 65-70 mg/dL Glucagon and other glycemic hormones are released into the circulation. 50-55 mg/dL Observable symptoms of hypoglycemia appear. ≤50 mg/dL Considered low value and abnormal for infants (requires further diagnostic test) < 50 mg/dL Impairment of cerebral function starts. Hypoglycemic symptoms with a plasma glucose level of ≤55 mg/dL (3.0 mmol/L) in an individual who is not receiving medications for diabetes require further evaluation. Healthy males will maintain plasma glucose of 55mg/dL to 60 mg/dL for several days, while healthy females will produce ketones faster and allow plasma glucose to decrease to 40mg/dL. Glucose tolerance tests may be performed but with great caution in patients with suspected hypoglycemia because the procedure can induce severe reactive hypoglycemia, causing loss of consciousness and even shock. The traditional diagnostic test for hypoglycemia is accompanied by prolonged (extended) fasting with non-essential (not life-sustaining) medications discontinued during the procedure. Symptoms of Hypoglycemia Neurogenic- tremors, palpitations, anxiety, and diaphorests Neuroglycopenic- dizziness, tingling, blurred vision, confusion, and behavioral changes Classification of Hypoglycemia 1. Drug-induced- insulin, alcohol, salicylates, sulfonamides, pentamidine 2. Critical illnesses- hepatic failure, sepsis, renal failure, cardiac failure, malnutrition 3. Hormonal deficiency- epinephrine, glucagon, cortisol, growth hormone 4: Endogenous hyperinsulinism- pancreatic beta cell disorders 5, Autoimmune hypoglycemia- insulin antibodies 6. Non-beta cell tumors leukemia, hepatoma, pheochromocytoma, lymphoma 7. Hypoglycemia of infancy and childhood- galactosemia, GSD, Reye's syndrome  DIABETES MELLITUS It is a group of metabolic disorders characterized by hyperglycemia resulting from defects in insulin secretion, insulin receptors or both. Fasting plasma glucose concentration of >= 126 mg/dl on more than one testing is indicative of DM. Glucosuria occurs when plasma glucose levels exceed 180 mg/dl (9.9 mmol) with normal renal function Ketosis develops in DM from excessive synthesis of acetyl-CoA, as the body attempts to obtain required energy from a stored fat in the absence of an adequate supply of carbohydrate metabolites. In severe DM, the ratio of B-hydroxybutyrate to acetoacetate is 6:1 The entire process of ketosis can be reversed by insulin administration  LABORATORY FINDINGS IN DIABETES MELLITUS increased glucose in plasma and urine (↑) increased urine specific gravity (↑) presence of ketones in serum and urine decreased blood and urine pH (acidosis) Electrolyte imbalance (↓Na, ↓K, ↓HC03) High serum osmolality CLASSIFICATION OF DIABETES MELLITUS Latent Autoimmune Diabetes of Adulthood (LADA) It is described as the Type 1a or 1.5 DM. It is also referred to as the slow immune-mediated DM or the slowly progressive insulin- dependent type 1 diabetes mellitus (SPIDDM). It is characterized by moderate hyperglycemia with gradual autoimmune destruction of the pancreatic beta cells that is common among adults. It is a form of adult-onset autoimmune T1DM which is ketosis-resistant. It may be presented as asymptomatic hyperglycemia without the need for insulin therapy in the early stages of disease management. It shares immunological features with both DM and T2DM (Rajkumar and Levine, 2022). Distinguishing feature: (+) Single specific islet cell autoantibody (GAD, *IA-2A, ZnT8, or insulin) Predominant autoantibody: GAD Predisposing factors: Low birth weight, severe smoking, advanced age, and familial history of autoimmune disease. Signs and symptoms similar to Type 1 DM: Polyuria, polydipsia, and weight loss Fulminant Type Diabetes (FT1D) It is formerly known as idiopathic type 1 DM or type 1b. It is strongly inherited and associated with the absence of B-cell autoantibodies. It is characterized by remarkably rapid and complete -cell destruction (Kaneko et al, 2017) It is a subset of type 1 diabetes with aggressive progression of hyperglycemia and ketoacidosis (Luo et al., 2020). Gestational Diabetes Mellitus (GDM) It is due to impaired ability to metabolize carbohydrates usually caused by a deficiency of insulin, metabolic or hormonal changes. It occurs during pregnancy and disappears after delivery but, in some cases, returns years later. It is a type of glucose intolerance with onset or first recognition during pregnancy (diabetic women who become pregnant are not included in this category). Screening should be performed between 24 and 28 weeks of gestation, except for those pregnant women categorized as high-risk individuals. The screening and diagnosis of GDM is through 2- hour OGTT. Diagnostic Tests: One-Step Method (with 75 grams glucose load, commonly used) Two-Step Method (50 grams initially; 100g glucose load as follow-up) Diagnostic Criteria for GDM (One- Step Method-IADPSG*) 1. 292 mg/dL 2. 1-hour sample: ≥ 180 mg/dL 3. 2-hour sample ≥ 153 mg/dL *IADPSG- International Association of Diabetes and Pregnancy Study Groups OTHER TYPES OF DIABETES MELLITUS 1. DM due to pancreatic disorder (pancreatogenic DM): chronic pancreatitis, malignancy (pancreatic cancer),or may be caused by pancreatectomy 2. DM related to endocrine disorders: Cushing's syndrome, pheochromocytoma, acromegaly, aldosteronoma and hyperthyroidism 3. DM caused by genetic syndromes: Down syndrome, Klinefelter's syndrome, Rabson-Mendengall syndrome, Leprechaunism, Huntington's chorea, Turner syndrome,etc. 4. DM associated with other exocrine diseases: Cystic fibrosis, neoplasia, and hemochromatosis 5. DM due to viral infections such as CMV and rubella 6. Drug-inducedor chemical-induced DM: Due to drugsor chemical inducers of B- cell dysfunction (dilantin and pentamidine) andthose that cause impaired insulin action (thiazides and glucocorticoids) CUSHING’S DISEASE is a condition that happens when the body has too much cortisol, a hormone made by the adrenal glands. Cortisol is important for many body functions, including regulating blood sugar, controlling inflammation, and managing stress  PHEOCYTOCHROMA Pheochromocytoma is a rare type of tumor that forms in the adrenal glands, which are located on top of your kidneys. These tumors cause the adrenal glands to produce too much of certain hormones, particularly adrenaline and noradrenaline, which are hormones involved in your body’s “fight or flight” response is a condition that occurs when the body produces too much growth hormone (GH) after adulthood. This excess hormone causes the bones and tissues to grow larger than normal, especially in the hands, feet, and face. It usually develops slowly over time is a condition where the thyroid gland makes too much thyroid hormone. The thyroid is a small, butterfly-shaped gland in the neck that controls how fast your body uses energy (metabolism). When the thyroid makes too much hormone, everything in the body speeds up Graves' disease (the most common cause): An autoimmune disorder where the immune system attacks the thyroid, making it overactive. is a condition where the thyroid gland doesn't make enough thyroid hormone. Since the thyroid controls your metabolism, having too little thyroid hormone makes your body's processes slow down. Hashimoto’s disease (most common cause): An autoimmune disorder where the immune system attacks the thyroid, causing it to produce less hormone  DOWN SYNDROME is a genetic condition that occurs when a person is born with an extra copy of chromosome 21. Normally, people have 46 chromosomes (23 pairs), but individuals with Down syndrome have 47 because of the extra chromosome. This extra genetic material affects how the body and brain develop, leading to certain physical features and developmental delays  KLINEFELTER SYNDROME Klinefelter syndrome (XXY) are at a higher risk of developing type 2 diabetes and other conditions related to blood sugar regulation. This happens because men with Klinefelter syndrome often have lower levels of testosterone, which can affect how the body processes insulin. Insulin resistance (when the body doesn’t respond to insulin properly) is more common in individuals with Klinefelter syndrome, which can lead to elevated blood sugar levels and, over time, diabetes  RABSON-MENDENHALL Rabson-Mendenhall syndrome is a rare genetic disorder that affects how the body responds to insulin, the hormone that controls blood sugar levels. In this condition, the body's cells are severely resistant to insulin, meaning they can't use it properly to take in glucose (sugar) from the blood. This leads to high blood sugar levels, which can cause many health problems  LEPRECHAUNISM Leprechaunism, also known as Donohue syndrome, is a rare genetic disorder that affects how the body processes insulin, leading to severe insulin resistance HUNTINGTON’S CHOREA Huntington's chorea, also known simply as Huntington's disease, is a progressive genetic disorder that affects the brain, leading to a decline in physical and mental abilities. It is characterized by uncontrolled movements (chorea), emotional disturbances, and cognitive decline  TURNER’S SYNDROME Turner syndrome is a genetic condition that affects females. It occurs when one of the X chromosomes is missing or partially missing, leading to a variety of physical and developmental features CYSTIC FIBROSIS is a genetic disorder that primarily affects the lungs and digestive system. It occurs when a mutation in the CFTR gene leads to the production of thick and sticky mucus in the body  CMV aka as KISSING DISEASE Cytomegalovirus (CMV) is a common virus that belongs to the herpesvirus family. It is often harmless for most people, but it can cause serious health problems in certain groups, such as newborns, pregnant women, and people with weakened immune systems.  RUBELLA also known as German measles, is a contagious viral infection that is generally mild in children but can cause serious complications if contracted during pregnancy. PANCREATOGENIC DIABETES MELLITUS (PDM) aka known as Type 3C DM develops as an outcome of a pancreatic disease such as pancreatitis or carcinoma it is characterized by insulin deficiency and loss of pancreatic polypeptide