PBL Week 11 Flashcards
What are the biochemical pathways involved in glucose metabolism?
5 major pathways - glycolysis (breakdown of glucose to pyruvate for energy), glycogenesis (storage of energy as glycogen), gluconeogenesis (generation of glucose from pyruvate, which itself is generated from non-carbohydrate molecules e.g amino acids and lipids) glycogenolysis (generation of glucose from glycogen) and the pentose phosphate pathway (a side pathway).
What is the anatomical structure and function of the pancreas?
The pancreas is divided into 5 parts:
Head - widest part, lies within the c-shaped curve of the duodenum and connected by connective tissue.
Uncinate process - a projection arising from the lower part of the head and extending to lie beneath the head and the body of the pancreas.
Neck - located between the head and the body.
Body - centrally located, crossing the midline of the human body to lie behind the stomach.
Tail - the left end of the pancreas that lies with close proximity to the spleen.
The pancreas is a mixed organ - contains an endocrine and an exocrine function.
The exocrine pancrease releases salts and enzymes into the duodenum, neutralising the gastric acid there using bicarbonate. The enzymes released are amylase (breaks down starch), lipase (breaks down triglycerides) and proteolytic enzymes, that are activated in the duodenum to break down proteins.
The endocrine pancreas releases hormones into the blood stream. There are 3 cell types within the islets of langerhans; alpha cells (releases glucagon that breaks glycogen down to glucose), beta cells (releases insulin that converts glucose to glycogen) and delta cells (release somatostatin, which inhibits both glucagon and insulin.
How are glucose levels controlled in the body and what is the role of insulin?
If the brain detects that the blood sugar is low, glucagon release is promoted. Alpha cells release glucagon, which moves to the liver where it promotes the breakdown of glycogen to glucose, which raises the blood sugar levels. If the blood sugar is high, insulin release is promoted. Beta cells release insulin, which travels to the liver to convert excess glucose to glycogen, lowering the blood sugar. Within the liver and certain tissues, these hormones can also promote the conversion of glucose into fats (lipogenesis) or vice versa (lipolysis).
The processes that are promoted by insulin in the “fed” state are: glycolysis, glycogenesis, lipogenesis.
The processes that are promoted by glucagon in the “fasting” state are: gluconeogenesis, glycogenolysis, lipolysis.
Insulin itself is a small protein hormone made of 2 chains, an A chain and a B chain. As small proteins aren’t often stable, a larger protein chain is created, which folds itself into the structure required for insulin. It is then removed, leaving only the 2 small chains, joined by 3 disulfide bridges.
What are the different gentetically-inherited metabolic carbohydrate disorders?
Galactosemia - First starts when drinking milk. Lactose is usually broken down into glucose and galactose, with this disease the enzymes needed to further break down galactose are missing, leading to toxic build ups of galactose/galactose-1-phosphate. Symptoms include lethargy, jaundice, liver dysfunction, kidney disease, weight loss, cataracts and intellectual disability. Treated by removal of galactose (dairy) from diet.
Hereditary Fructose Intolerance - First starts when eating fruit/table sugar. Fructose is usually broken down to Fructose-1-phosphate, in this disease the enzyme which breaks this product down (aldolase B) is deficient, leading to an accumulation of Fructose-1-phosphate and the trapping of phosphate, inhibiting glucose and ATP production. Sympotoms include failure to gain wait, vomiting, liver dysfunction, kidney defects and hypoglycaemia. Treated by removing fructose and sucrose from diet.
Fructose Biphosphatase Deficiency - Fructose biphosphate is an enzyme involved in gluconeogenesis (creation of glucose from pyruvate). In this disease, there isn’t enough of this enzyme for this process to occur. Because of this, severe hypoglycaemia sets in after around 12 hours of fasting, leading to an enlargement of the liver. The treatment is an IV drip of glucose and the avoidance of fasting.
Glycogen Storage/Von Gierke’s disease - The disease impairs the liver’s ability to convert glycogen to glucose (glycogenolysis). Leads to the accumulation of glycogen in the liver, enlargement of liver, hepatoma later in life and hypoglycaemia. The treatment includes the continuous supplying of glucose to the digestive tract and frequent feedings of carbohydrates or slow release glucose before bed.
What is the biochemsitry and physiology of diabetes mellitus?
Type 1 - caused by an inability to synthesise insulin in response to high levels of glucose. This is caused by an autoimmune destruction of the beta cells of the pancreas. Leads to dehydration (as the body flushes out the excess sugars in urine) and a lowering of the blood PH (as the body turns to other, acidic molecules for energy). Insulin levels can decrease as we age, allowing high levels of sugar into the blood, which can attach to proteins and inhibit their function. Is treated by the injection of insulin (produced by bacteria or yeast).
Type 2 - caused by both insulin resistance in cells as well as a decrease in function by beta cells. Often caused by obesity, lack of exercise or old age. Symptoms include frequent urination, increased thirst, increased hunger and weight loss. Is treated by regular exercise and a healthy diet, as well as not eating foods too high in sugar.
What are the labratory investigations involved in the diagnosis of glucose related metabolic diseases?
Diabetes can be diagnosed by a fasting plasma blood glucose test (FPG). This measures the amount of sugar in the blood without the effect of food intake, measuring the rate of glucose metabolism. An oral glucose tolerance test (OGTT) is similar, giving the patient a set amount of glucose and measuring their blood sugar at intervals to determine the rate of glucose metabolism.
Glactosemia is diagnosed through newborn screening, taking blood from the heel or testing the infant’s urine for the 3 enzymes needed to break down galactose.
Hereditary fructose intolerance is diagnosed through a genomic DNA screening or an enzyme assay from a liver biopsy.
Fructose bisphosphate deficiency is diagnosed by measuring the enzyme’s levels in cultured lymphocytes and confirmed by the mutation of the gene FBP1, which encodes the enzyme.
How was insulin produced to treat diabetes and how is it produced now?
Insulin used to be harvested from the pancreas of dead pigs. Nowadays, however, we have much more efficient ways of creating it. Insulin can be created in a lab by removing a plasmid from a bacterium, cutting out part of the DNA and replacing it with the human insulin gene. The bacterium can then be placed into a fermentation tank where it can grow, replicate and produce insulin, which can be harvested.
What are the psychological effects the diagnosis of a long term illness might have on a person?
The psychological effects include:
- persistent worries and fears about the illness and its long-term effects
- fear of dying
- fear of the hospital or medical procedures
- persistent sadness, anger, irritability, or excessive moodiness
- changes in self esteem
- concerns about physical appearance and body image
- behavior problems
- social difficulties, especially getting ostracised.
What is the effect of ethnicity on type 2 diabetes?
Afrocarribean and south asian people are more likely to develop insulin resistance. The reason this is thought to happen is due to people of these ethnicities have certain genes that affect fat processing, leading them to accumulating more fat around the abdomen - particularly around the liver and pancreas. This leads to a increased risk of insulin resistance.
