GEP (Life Maintenance) Week 5 Flashcards
Identify the locations of the pancreas
Majority of pancreas has exocrine function.
1-2% endocrine glands (Islets of Langerhans)
What is the difference between Exocrine and Endocrine
whereas exocrine glands secrete substances into a ductal system to an epithelial surface, endocrine glands secrete products directly into the bloodstream
What are the different cells in the Pancreas and what do they secrete
Cell:Secretes
* Alpha: Glucagon
* Beta: Insulin
* Gamma: Pancreatic polypeptide
* Delta: Somatostatin
* Epsilon: Ghrelin
Identify the locations of the cells with this cross-section of the pancreas
What are the blood supply and innervation to the pancreas
Arterial:
Supplied by pancreatic branches of splenic artery.
Head also receives supply from superior and inferior pancreaticoduodenal arteries.
Venous:
Head -> drains into superior mesenteric branches of hepatic portal vein.
Rest of pancreas -> splenic vein
Innervation:
Sympathetic -> greater and lesser splanchnic nerves
Parasympathetic -> vagus nerve (CN X)
What are the steps to the pancreas releasing Insulin
Step 1: Glucose ingestion
Step 2: Activation of the pancreas via GLUT-2 receptors
Step 3: Beta cells release insulin
Step 4: Insulin migrates to target cells and enters the cell (Fat and muscle)
Step 5: GLUT-4 transporters migrate to the cell surface membrane to allow for uptake of glucose
How is insulin produced
- Insulin is produced in the beta cells in the form of Preproinsulin.
- Preproinsulin (Alpha chain, bet chain, C-peptide and a signal peptide) is then broken down into proinsulin (alpha chain, beta chain and C-peptide)
- When insulin is signalled to be released it is broken down into its final form insulin
- But the C-peptide is important as it’s a marker for endogenous production of insulin
What are the definitions of: Gluconeogenesis, Glycogenolysis, Glycogenesis, Lipolysis, Lipogenesis, Proteolysis, Glycolysis
- Gluconeogenesis - De novo synthesis of glucose from non-hexose precursors
- Glycogenolysis - Glycogen broken down into glucose
- Glycogenesis - Formation of glycogen from glucose
- Lipolysis - The breakdown of fats and other lipids to release fatty acids
- Lipogenesis - Metabolic formation of fat
- Proteolysis - Breakdown of proteins into amino acids
- Glycolysis - Breakdown of glucose to make energy
what are the affects of insulin
Insulin affects:
* Adipose tissue - Increases glucose uptake
* Muscle cells - increases protein synthesis and glycogenesis, Decreases glycogenolysis,
* Liver cells - Fatty acid metabolism
What are the pathway of insulin
Pathway of insulin:
* Proinsulin -> insulin and C-peptide
* Insulin -> liver, muscle and fat cells, (Skeletal muscle is a predominant target)
* Insulin enters via GLUT2 transporter and activates the PI3K-AKT pathway
* GLUT4 vesicles ->cell surface and are expressed
Proinsulin is cleaved to form insulin and C-peptide both of which are excreted from the beta cells together.
The insulin then travels around the body to muscle and fat calls, (Skeletal muscle is a predominant target)
Insulin enters cells with the GLUT-2 transporter and activates the PI3K-AKT pathway
GLUT-4 vesicles move to the surface of the cell and are expressed
(Glucose can also enter here due to the receptors high capacity for glucose but low affinity)
Describe the production of glucagon
- GLP-1 inhibits release of glucagon
Produced in several parts of the body including:Pancreatic islet alpha cells, intestinal enteroendocrine L cells and some neurons in the brainstem and hypothalamus - Pancreas = Proglucagon to Glucagon
- Intestine + Brain = Proglucagon to Glucagon-like peptide 1 (GLP-1) and glucagon-like peptide 2
- Secreted in response to hypoglycemia, prolonged fasting, exercise and protein-rich meals.
- Normal basal level of Glucagon = 20 pmol/l rises 3-4 above basal state during hypoglycemic event or exercise
What are the actions of glucagon
The glucagon receptor is a seven transmembrane G protein-coupled receptor.
Expressed mainly by the liver but also by the kidneys, adrenal glands, GI tract, and pancreas.
Promotes hepatic glycogenolysis and gluconeogenesis
Inhibits glycolysis and glycogenesis
Give a breif overview of G-Protein
Activation and Suppression of Insulin and Glucagon
- Eating and fasting are not the only way insulin and glucagon levels are changed.
What is glucose
- Glucose is a 6-carbon structure with the formula C6H12O6 it is a monosaccharide as it cannot be
- broken down further by hydrolysis.It is the only source of energy the brain can use. As the brain has no resources to safely breakdown other sugars i.e lactose (Disaccharide) and fructose (A different monosaccharide).
- Glucose is then used via the Kreb’s cycle to make ATP.
give and overiew of Type 1 diabetes: Signs and symptoms, risk factors and definition
Definition:
Absolute insulin deficiency leading to hyperglycaemia. Usually caused by an immune-mediated process.
Signs and symptoms:
The big 3:
*Polyuria
*Polydipsia
*Weight loss
Other key ones:
*High blood sugar
*Lethargy
Risk Factors
*Genetic predisposition
-Especially HLA
*European
*Some viruses
*Dietary factors
What is the pathophysiology of type 1 diabetes
What is the management of type 1 diabetes
Insulin
give and overiew of Type 2 diabetes: Signs and symptoms, risk factors and definition
Definition:
Progressive disorder that occurs as a result of deficient insulin secretion and increased insulin resistance.
Signs and symptoms:
The big 3:
* Polyuria
* Polydipsia
* Weight loss
However Often asymptomatic.
Risk factors:
Older age
Obesity
Gestational diabetes
Hypertension
Family history
What are the diagnostic criteria of type 2 diabetes
With symptoms -> 1 test needed
Without symptoms -> 2 tests on separate occasions must be done.
FG: fasted glucose
HbA1C: Glycated hemoglobin is a form of hemoglobin that is chemically linked to a sugar. Most monosaccharides, including glucose, galactose and fructose, spontaneously bond with hemoglobin when present in the bloodstream
What is the pathophysiology of Type 2 diabtes
What is the management of type 2 diabetes
What are the complications of uncontrolled diabetes
Macrovascular:
Cardiovascular disease
Stroke
Diabetic foot
Microvascular:
Retinopathy
Nephropathy
Neuropathy
Other:
DKA
Hypoglycaemia
What is DKA, the signs and symptoms you get and the risk factors associated with it
Definition:
Acute complication of diabetes that’s potentially fatal. Characterised by hyperglycaemia, ketosis and acidosis. It is often the first presentation in a young person of T1DM.
Signs and symptoms:
Known diabetes
Nausea
Dehydration
Hyperventilation (Kussmaul)
Reduced consciousness
Abdo pain
Acetone breath
Risk factors:
Inappropriate insulin
Infection
Myocardial infarction
Drugs
Cushing’s syndrome
What is the pathophysiology of DKA
what is the management of DKA
The best way to remember is FICKLE accnorym
What are the signs and symptoms of hypoglycemia
Below 3.3 blood glucose:
Sweating, shaking, hunger, nausea, anxiety.
Below 2.3 blood glucose:
Weakness, vision changes, confusion, dizziness.
What is the immediate management of hypoglycemia
Blood glucose >4:
Small carbohydrate snack, or next meal if it is due.
Blood glucose <4:
If patient is conscious -> fast-acting carbohydrate e.g. glucose tablet, fruit juice
Repeat every 15 minutes, max 3 treatments.
If patient unconscious -> IV glucose
Give an overview of diabetes insipidus
Polyuria, polydipsia and production of large quantities of hypotonic urine.
Two types:
Central -> due to low levels of ADH released from hypothalamo-pituitary axis.
Nephrogenic -> renal insensitivity to ADH.
May present as medical emergency -> hypernatraemia.
Give an overview of gestinational diabetes
- Hyperglycaemia in pregnancy.
- Resolves after the completion of pregnancy.
- Resistance to insulin increases in pregnancy, and usually beta cells can compensate, if they can’t -> gestational diabetes.
Risk factors:
* Obesity
* Prior-GDM
* PCOS
* Age
* Family history T2DM
* Previous big baby
Complications:
T2DM -> majority
Big baby
Maternal hypertension
Neonatal hypoglycaemia
MICRA insulin
One of the sneaky effects of insulin is that it causes potassium to leave the blood supply and enter into cells. This effect results in hypokalaemia which is responsible for the tingling and spasms Mrs Jenkin’s mentioned.
MICRA Metformin
MICRA Sulphonylureas
MICRA Thiaziladiones
MICRA GLP-1 Agonists
MICRA DDP-4 Inhibitors
SGLT-2 Inhibitors
side effects to have a mild diuretic effect + decrease sodium, -> sodium homeostasis and a decrease in plasma volume and BP
