Diabetes mellitus Flashcards
Factors that can increase blood glucose concentration
Somatotropin
Adrenal gland (cortisol and adrenaline)
Ghrelin (hunger hormone)
PP cells and Pancreatic polypeptide
Somatotropin
The growth hormone
Secreted by- anterior portion of the pituitary gland
Major role in- promoting expansion of the epiphyseal growth plates to promote the growth of long bones.
– also promotes, the growth of muscle and skin and many of the internal visceral organs
Due to growth requiring increased cell division, somatotropin stimulates increased protein synthesis.
– significantly increases blood glucose concentrations by stimulating gluconeogenesis (creation of new glucose) in the liver whilst inhibiting the uptake of glucose by liver hepatocytes.
Adrenal gland and cortisol
Adrenal medulla- has a population of cells called chromatin cells which primarily produce the hormone adrenaline.
– adrenaline can increase blood glucose levels, as the flight or flight response requires extra energy, so this will stimulate liver to release more glucose into blood.
Adrenal cortex- reduces steroid hormones including cortisol.
Cortisol- released during biological stress such as physical injury or being deprived of food.
– promotes gluconeogenesis by initiating lipolysis (fat breakdown) and protein breakdown.
– newly created glucose is then released into the blood increasing the blood glucose concentration.
Islets of langerhans
Beta cells- 70%- insulin (increase in glucose conc)
Alpha cells- 5%-20%- glucagon (decrease in glucose conc)
Epsilon cells- Ghrelin
PP cells- Pancreatic polypeptide
Ghrelin
Hunger hormone
Released from epsilon cells, and stomach, brain, lungs and kidney
Usually peaks before major meals
Ghrelin, binds to receptors in hypothalamus to elicit sensations of hunger
– increases food intake, eventually leading to increase blood glucose levels
Pancreatic polypeptide
Satiety hormone, switches off hunger by promoting the feeling of being satisfied (satiated) after eating.
levels peak 15-30 mins after eating, but remain in blood for 4-5 hours
Secretion reduced when- overweight or obese people, which may lead to overeating and inc BGL. RF of type 2 DM.
Secretion upregulated:
– anorexia nervosa, contributing to undereating and underweight
Insulin response
Only hormone in the body to lower the blood glucose levels.
Decrease in glucose in blood- beta cells trigger release of insulin
Insulin circles the body before binding to insulin receptors which are present on the surface of most cells in the body.
When insulin binds, protein channels called glucose transporters (GLUT’s) shifted from cytoplasm of cell to plasma membrane. GLUT 4, creates a simple channel and glucose moves into cell via facilitated diffusion.
Type I DM
Insulin dependant diabetes mellitus
– individuals need to inject insulin to survive
1 in 10 patients, usually diagnosed in children and young adults
Causes:
– well understood
– autoimmune disease, which leads to the destruction of the beta cells.
– thought to be triggered by viral infections like the mumps
– without active beta cells, insulin can not be produced, so blood glucose conc is going to be higher
– patient will show a pronounced hyperglycaemia
Early stages:
– immune cells can be seen infiltrating the islets of langerhans, which indicates that immune reactions are taking place which ultimately leads to beta cells destruction, then leading to type I DM.
Type II DM
Can be diagnosed at any age.
Causes:
– poorly understood
– appear to be related to diet, lifestyle and obesity
– patient becomes resistant to the action of insulin, it has been speculated that something may interfere with the ability of insulin to bind to its receptor.
– end result similar to that of Type I DM. Leading to hyperglycaemia.
Most common diabetes- 9 in 10 patients with diabetes
Gestational diabetes
Affects 4% of pregnant women
Cause:
– still not fully understood, but thought to be linked to high levels of placental hormones during pregnancy.
mothers with this have increased chance of getting type II DM.
Excess glucose can cross the placenta leading to increase fat deposition in the foetus and high birth-weight babies which often require assisted delivery
Symptoms of DM
Hyperglycaemia:
– key defining feature
– oral glucose tolerance test
Polyuria and glcosuria:
– increased urine output (polyuria), caused by glucose-rich filtrate accumulating in the kidney tubules.
– presence of sugar in urine (glycosuria)
– detection using- urinalysis strips, dipped into the patients urine
polydipsia:
Excessive thirst
– due to polyuria, the blood becomes more concentrated
– osmoreceptors in hypothalamus measure osmotic level of blood, will detect higher conc
- -thirst centres are activated and desire to drink water increases
ketoacidosis:
Poorly controlled diabetes, the absence of a normal insulin response put the body into a state of starvation, as the cells of the body are unable to uptake glucose.
– cortisol is released (and does its function),
– ketones released during lipolysis, accumulate and lower pH.
– this is a medical emergency and should be detected and treated quickly.
Signs:
– ketones have a fruity aroma, so:
– sweet smell on someones breath, and associated with their urine. (Urinalysis test strips can detect this)
Associated pathologies with DM
Peripheral Vascular Disease (PVD):
– poorly controlled DM can be damaging to blood vessels.
– excess glucose can damaged endothelial lining, leading to atherosclerotic occlusion of blood vessels.
Signs of PVD:
– Pains in calf muscles during exercise, which can lead to limping. (Claudication).
The diabetic foot:
– Blood flow to the foot is quite sluggish anyway, but vessels that have suffered atherosclerotic occlusion, reduces the blood flow even more to the feet.
– each nerve has its own capillary blood supply and atherosclerotic occlusion down the legs to the feet leads to poor perfusion of the nerve fibres which gradually atrophy and die away.
– causes peripheral neuropathy (lack of sensation to the hands and feet).
– peripheral neuropathy, particularly dangerous as the patient may not notice injuries, when skin is broken, leading to increased chance of infection
– autonomic neuropathy- where there is damage to the nerves that control autonomic body functions.
soles of the feet have a huge number of sweat glands, if these nerve fibres atrophy due to neuropathy, then skin can then no longer produce sweat. causing it to dry out and crack. Makes it easier for pathogen entry, increasing the likelihood of infection.
Infection initiates a vigorous inflammatory response where phagocytic leukocytes such as neutrophils migrate into the infected skin and degranulate releasing their digestive enzymes. causing the skin to macerate and ulcerate.
Coronary heart disease and Myocardial Infarction:
– atherosclerotic occlusion of the coronary arteries:
—- usually associated with central chest pain (angina pectoris), due to poor blood supply to the myocardium
—- in patients with sensory neuropathy, angina pain may not be present, even when the coronary arteries are significantly occluded (silent angina).
—- if the fatty plaque ruptures, it can lead to thrombosis resulting in myocardial infarction (heart attack), which is the most common cause of death in patients with diabetes.
Diabetic nephropathy:
– excess sugar can cause damage to the delicate filtration membranes in the kidney nephrons.
– this can progressively reduce renal function, leading to chronic renal failure.
Diabetic eye disease:
– diabetic retinopathy- abnormal growth of blood vessel in the retina.
these vessels often leak, resulting in the accumulation of damaging exudates in the retina.
Dark spots may be experienced
Diabetes is the leading cause of blindness in the UK.
Patients with chronic hyperglycaemia are prone to diabetic retinopathy.
– opportunistic infections:
the presence of excess sugar in the blood and bodily secretions such as mucus, provides an ideal substrate to encourage growth of micro-organisms.
can cause genital or oral thrush.
