Pathophysiology Flashcards
(22 cards)
Name the 4 tests used to diagnose diabetes
RPG
Fasting plasma glucose
OGTT
Glycosylated haemaglobin - HbA1C
how is random plasma glucose used to help diagnose diabetes?
> 11.1 mmol
warrants further investigation - use other tests to diagnose.
Why do diabetics have polyuria and polydipsia?
Increased blood glucose -
Increased glucose excretion
Water follows (increased osmolality of filtrate)
Why do diabetics get blurred vision?
the refractive index of the lens changes due to the presence of glucose
What are the criteria for a positive fasting plasma glucose test?
> 7 mol
On 2 separate occasons.
What is the criteria for a positive OGGT?
11.1 mmol
What may cause a false positive/negative HbA1C?
HbA1C measured the amount of glycosylated Hb (not the anount of glusoce). If the amount of Hb is affected by anything (eg anaemia), the result cannot be used for a diagnosis of diabetes.
What are the criterai for a positive HbA1C test?
48 mmol/mol or above
in the absence of any history of Hb disorders
Name some situations/conditions in which an HbA1C test would not be an accurate test for diabetes
Iron deficienct anaemia
Renal impairment
Pregnancy
recent blood transfusion
Would you ever perfrom an OGTT AND an HbA1C to dignose diabetes?
NO
some cases can provide a negative result in one and a positive in the other. Only 1 of these test is required for a diagnosis. To do more than that could confuse the picture.
What are the major hormones involved in glucose homeostasis?
Insulin
Glucagon
Incretins
What is the role of insulin?
decreases blood glucose levels by:
- inhibits breakdown of glycogen in liver
- enhances storage of glucose as glycogen
- enhances peripheral glucose uptake
How is the secretion of insulin stimulated?
What is the pathophysiology?
Glucose in blood stimulates the glucose transporter 2 (GLUT2) receptors on beta cells in the pancreas.
Glucose transported into cell and phosphrylated.
Ca2+ channels open allowing Ca2+ in.
Ca2+ stimulates exocytosis of insulin endosomes.
How doe the duodenum help regulate blood glucose?
Glucose in the duodenum stimulates L-cells to secrete glucagon like peptide GLP (an incretin).
GLP acts on the pancreas to
- increase the secretion of insulin, and
- decrease the secretion of glucagon.
How is glucose transported accross membranes?
Diffusion - but it is hydrophilic so this is rate limiting
GLUT2 in beta cells
GLUT4 in tissue - expression is regulated by insulin.
How does insulin encourage glucose uptake from blood into tissue (reducing blood glucose level)?
2 insulin moelcules adhere to receptor on taget tissue cell (eg myocyte).
Phosphorylation downstream
Translocation of GLUT4 onto cell membrane
GLUT4 facilitates glucose transport into cell.
What is the pathophysiology of insulin resistance?
Insulin binds to receptors on cell membranes, but the downstream phosphorylation does not occur.
GLUT4 transporters are therefore not translocated to the membrane
Glucose is not transported from the blood into the cells.
What is the incretin effect?
incretins such as GLP1 are secreted by the duodenum post prandially in response to glucose. GLP1 acts is the pancreas to increase insulin secretion, and reduce glucagon.
The incretin effect is the fact that oral glucose has a much greater influence on the amount of insulin produced than IV glucose does.
How is the incretin effect affected by T2DM?
The amount of insulin released in response to glucose meal (vis incretin pathway) is diminished.
(in addition, the body id resistant to whatever insulin is released - double trouble!)
How is the secretion of glucagon affected by T2DM?
Normally, glucagon is secreted in response to a low blood glucose level, and glucagon secretion is suppressed in blood glucose is high.
T2DM causes the loss of glucagon secretion supression. Therefore ther will be high blood glucose and glucagon.
How is glucsoe reabsorbed into the blood in the kidney?
At what blood glucose level overwhelms this system, forcing some glucose into the urine?
Through SGLT1 and SGLT2 transporters in the proximal tubule.
Beyond 12 mmol, glucose is excreted.
How does T2DM affect glucose reabsorption in the kidney?
SGLT1 and SGLT2 normally reabsorb 100% of glusoce below a blood glucose level of 12mmol.
In T2DM, SGLT1 and SGLT2 reabsorb glusose up to blood glucose level of 14 mmol.
T2DM increases the amount of glucose that can be reabsorbed thereby maintaining a high blood glucose level.
