Type 1 Diabetes Flashcards
What occurs in immune mediated T1DM?
There is lymphocytic infiltration of the beta-cells of the pancreas, causing destruction of them.
Which genes are commonly associated with the development of autoimmune T1DM, and what do they do?
HLA-DR3 and DR4 - form antibodies against either the islet cells or the insulin itself.
What factors are considered to contribute towards the development of T1DM?
Hereditary, viral infection or toxic agents
- viral infections stimulate antibodies against the viral protein, which may be antigenically similar to the beta -cells in the pancreas
What is idiopathic T1DM associated with?
Beta-cell destruction without any autoimmune markers or HLA association.
T1DM is characterised by an absolute insulin deficiency, and so causes what changes in the body?
Glucose can’t enter muscle or adipose tissue
Gluconeogeneis is no longer inhibited
Overproduction of glucagon stimulates gluconeogensis and glycogenolysis
All this means plasma glucose levels rise
At what point in the disease is glucose detectable in the urine?
When the maximum tubular reabsorption capacity of the kidneys is exceeded.
What are the two main pathologies that occur when the glucose starts to be excreted in the urine?
Glycosuria
Osmotic fluid loss leading to sever hypovolemia
Why do people with T1DM have an increased urge to eat?
Because insulin is needed for glucose to enter striated muscle and adipocytes, these tissues no longer have glucose avail ale as a substrate. The brain interprets this as starvation and urges us to eat more.
Why does thirst occur in T1DM patients?
The body is attempting to dilute the blood and decrease the plasma glucose levels.
What effect does continued insulin deficiency have on fat tissue.
There is increase lipolysis, because insulin can’t inhibit it
The increased lipolysis increases the FA levels in the blood
What happens to the increased number of FAs in people with T1DM?
They are metabolised into keto acids in the liver
Why does the body create keto acids?
To be used by neural and muscle tissues for energy
What happens when the keto acid pathway is saturated?
The pH of the blood falls, causing metabolic acidosis as the bicarbonate concentration falls and DKA ensues
Ketone bodies become present in the urine (also increase fluid loss).
How does transient hyperkalaemia occur in DKA?
In the body, intracellular potassium is swapped for extracellular hydrogen in an attempt to stop the acidosis. However this does mean more potassium is being excreted by the kidneys, and total body potassium is depleted.
What re the symptoms of T1DM?
Abnormal thirst Increased need to urinate Increased appetite Weight loss Fatigue General itching Suppressed wound healing Blurred vision Hyperglycaemia
