Pathophysiology of Diabetes Mellitus Flashcards
What are the three major endocrine cells found in the pancreas?
- glucagon
- insulin
- somatostatin
What stimulates an insulin increase?
- Amino acids/ fatty acids
- Gastrointestinal hormones
- parasympathetic system
- increase in glucose
What may cause a decrease in insulin secretion?
- Stress
- Symapthetic system
What occurs when there is an increase in plasma gluocse?
- stimulation of beta cells
- increase of insulin
- at the liver -> glycolysis, glycogenesis, lipogenesis
What is type I diabetes?
an absolute deficiency of insulin
destruction or loss of function of pancreatic B cells
most often seen in canine patients
What is type II diabetes?
Lack of insulin action/ response to insulin
How can you define diabetes?
high and persistent hyperglycaemia
What causes glucotoxicity?
Persistent hyperglycaemia
Why does hyperglycaemia cause increased polyuria?
- increased blood glucose leads to dehydration
- stimulation of ADH and thirst reflex
What is GLUT-4?
Glucose transporter responsible for glucose uptake into fat and muscle cells
What stimulates a glucagon release?
- decrease in glucose
- increase in amino acids
- increase in cortisol
What are the three ways that catecholamines act on the glucose pathway?
- Primarily inhibiting insulin secretion
- B2 adrenergic stimulus
- A2 adrenergic stimulus increases release of GH stimulaating hormones
- GH stimulates glucose uptake by cells
What is type I diabetes usually preceded by?
a period of pancreatitis
What is the effect of insulin resistance?
B-cell growth and proliferation- hyperinsulinaemia
What is the effect of oxidative stress?
B-cell failure, diabetes
What is the effect of glucotoxicity?
- Oxidative stress
- ER stress
- Hypoxic stress
- Cytokine induction
What needs to be lost for type II diabetes to develop?
Loss of beta cells
* causes an increased demand for insulin
* leads to increased production of islet amyloid polypeptide
How can lack of insulin explain weight loss?
results in un-opposed adipose tissue lipolysis and muscle proteolysis, resulting in weight loss
What is the effect of uncontrolled oxidation of fatty acids?
- very high ketone production
- resulting in ketoacidosis
- ketoacidosis is then a fatal consequence of uncontrolled or undiagnosed diabetes
What receptor is glucose reabsorbed through?
SGLT-2
What does glucose cause an increase of within the kidney tubule?
increase in osmotic pressure, increasing the urine output
glucosuria is also linked to increased incidence of UTI
Explain ketoacidosis as a result of diabetes
- Not enough insulin, body cannot use glucose as an energy store
- Therefore the body breaks down ketones
- Ketoacidosis
- Increased thirst and urination as the body attempts to expel ketones from the body
What is the function of kussmaul respiration?
- H+ acid gain
- Overwhelms the normal buffering system
- Body must therefore lose acid
- Increased respiratory rate
- Renal loss
- Vomiting
What is the polyol pathway?
- Increased glucose leaves to increased sorbitol
- Sorbitol= osmotic damage and cell death
- SDH can convert sorbitol into fructose
Where in the body is the SDH enzyme not present?
Not present in the lens, retina, nephron and neurone
How does excess glucose cause blurred vision?
- Glucose is driven towards sorbitol formation
- osmotic stress
- lens swelling
- myopic change
- vacuole formation
- opacification
- diabetic cataract
What are the macrovacular complications of diabetes?
Athersclerotic plaque
* coronary arteries
* cerebral arteries
* peripheral vessels
What are the microvascular complications of diabetes?
Capillary damage
* retinopathy
* neuropathy
* nephropathy
What does hyperglycaemia cause?
in terms of vascular damage
increased blood flow to capillaries
thickening and altered composition of the basement membrane
What does increased vascular permeability cause?
Capillaries become leaky and dont function properly
accumulation of debris within vessels
Explain the process of retinopathy
- Degeneration and loss of pericytes
- Capillary wall weakening
- plasma leakage -> retinal edema -> hard exudate
How does hyperglycaemia damage nerves?
- neural and vascular cells do not require insulin for glucose uptake
- Hyperglycaemia leads to accumulation of sorbitol and fructose
- damage to schwann cells and pericytes
leads to plantigrade stance
How does cortsiol increase blood glucose?
- Increases gluconeogenesis
- Creating a state of insulin resistance
