Tiêu đề 2. ABNORMALITIES IN LIPOPROTEINAEMIA, GLYCOGEN INFILTRATION AND GLYCOGEN STORAGE DISEASES.pdf ✅

PHARMD GURU Page 1 ABNORMALITIES IN LIPOPROTEINAEMIA: Abnormality of lipoproteinemia can be either due to increased levels of lipoproteins which is referred as hyperlipoproteinemia or due to decreased levels of lipoproteins which is referred as hypolipoproteinemia. The most common type of abnormality is hyperlipoproteinemia. HYPER-LIPOPROTEINEMIA: It is found to be the major cause for coronary artery disease or atherosclerosis. It can be classified into two types based on the cause of pathology. 1) Primary Hyperlipoproteinemia: This is due to defect in the genetic catabolism. 2) Secondary Hyperlipoproteinemia: This is due to the presence of other co- morbidities (Eg:Diabetes, Nephrotic syndrome, myxedema) that are associated with elevated lipoproteins. WHO - Fredrickson Classification of Hyperlipoproteinemia: This system broadly classifies hyperlipoproteinemia into five categories based on the defect in genetic metabolism of lipoproteinemia.  Type I: It is due to deficiency of lipoprotein lipase enzyme resulting in increased levels of chylomicrons in blood and this leads to acute abdominal pain.  Type II: It is classified as Type Ila and Type Ilb Hyperlipoproteinemia. But Type Ila is most common and is also known as Familial Hypercholesterolemia. It is due deficiency of LDL receptors and results in increased LDL and cholesterol levels. Type Ilb is due to defect in apoB protein resulting in raised apoB levels that shoot up the levels of LDL and VLDL.  Type III: It is also called Familial Dyslipoproteinemia. This is due to defective expression of apoE lipoprotein and there will be increased levels of chylomicrons, intermediate density lipoproteins and triglycerides.  Type IV: It is also called Mild Hypertriglyceridemia. In this type; there will be slight increase in the levels of triglycerides. This is the most common risk factor for coronary artery disease. ABNORMALITIES IN LIPOPROTEINAEMIA, GLYCOGEN INFILTRATION AND GLYCOGEN STORAGE DISEASES
PHARMD GURU Page 2  Type V: It is almost similar to Type I Hyperlipoproteinemia. Both the levels of VLDL and triglycerides increase simultaneously. So it is also known as Severe Hypertriglyceridemia. This result in premature coronary vascular disease. HYPO-LIPOPROTELNEMIA: It can be categorized as Abetalipoproteinemia and Familial a lipoprotein deficiency. Abetalipoproteinemia is due to decrease in apoB lipoprotein which decreases levels of chylomicrons, VLDL, LDL that decrease absorption of fat soluble vitamins causing mental retardation due to decrease in the formation of myelin around nerve cells. Familial a lipoprotein deficiency is also known as Tangier disease. In this condition, the levels of lipoproteins decrease in ABC cassette mechanism which decreases HDL levels that predisposes as premature coronary artery disease. GLYCOGEN INFILTERATION:  During the cell injury, the cell loses its metabolic activity and function. As a result several substances get accumulated in the cell.  Glycogen is one of the major substances that get accumulated. Glycogen is stored in vacuoles that can be seen by staining the cells with Betacaramine and periodic acid Schiff Stain.  The glycogen accumulation is classically seen in patients with Diabetes Mellitus. In such patients there is decreased insulin secretion which raises blood glucose levels. This glucose is converted into glycogen and stored in cells.  Glycogen accumulation is also seen in chronic kidney impairment. In this condition GFR (glomerular filtration rate) is decreased and hence glycogen gets accumulated in glomerular cells. GLYCOGEN STORAGE DISEASES GLYCOGEN:  Glycogen, an important energy source, is found in most tissues, but is especially abundant in liver and muscle.  In the liver, glycogen serves as a glucose reserve for the maintenance of normoglycemia.  In muscle, glycogen provides energy for muscle contraction.
PHARMD GURU Page 3 GLYCOGEN STORAGE DISEASES:  Glycogen storage disease is the result of defects in the processing of glycogen synthesis or breakdown within muscles, liver, and other cell types.  The GSDs can be divided in three main groups:  Those affecting liver,  Those affecting muscle, and  Those which are generalized.  The liver glycogenoses:  GSD I  GSD III  GSD IV  GSD VI  GSD IX  GSD 0. GSD I (VON GIERKE DISEASE):  Caused by deficiency of the of glucose-6- phosphatase (G6Pase)  People with Type I GSD are able to store glucose as glycogen but not able to release it normally, with time the stores of glycogen build up in the liver causing the liver to swell (hepatomegaly). GLYCOGEN G1P G6P GLUCOSE SYMPTOMS:  Enlarged liver.  Low blood sugar (during fasting).  High levels of lactate, fats, and uric acid in the blood. G6Pase
PHARMD GURU Page 4  Impaired growth and delayed puberty. TREATMENT:  Initially glucose via a nasogastric tube.  As children get older, glucose is replaced with cornstarch taken orally. GSD III (CORI DISEASE): GSD III is caused by a deficiency of glycogen debrancher enzyme activity. The normal structure of glycogen has branches. In GSD III, glycogen is able to be partially broken down to release some glucose. However, the remaining glycogen that is not completely broken down has short outer chains and collects in the liver, muscle, and heart. The build-up of this atypical form of glycogen can cause damage to tissues. GLYCOGEN SYMPTOMS:  Swollen abdomen, low blood sugars on fasting, growth delayed during childhood.  Secondary symptoms: Problems with muscle weakness. DIAGNOSIS: Liver biopsies. Biopsy of the liver shows inflammatory changes (swollen liver cells) with great elevations of abnormal structured glycogen content and a deficiency of the debrancher enzyme (GDE). TREATMENT:  Protein supplements for muscle disorder. GSD IV (ANDERSEN DISEASE):  GSD IV is caused by a deficiency of glycogen branching enzyme. The normal structure of glycogen is formed by branches. The absence of glycogen branching enzyme leads to formation of glycogen with fewer branch points and longer outer chains than normal  Abnormally structured glycogen forms. G1P G1P GLYCOGEN DEBRANCHER ENZYME UDGP GLYCOGEN GLYCOGEN DEBRANCHER ENZYME