Diabetes notes.docx

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McMaster University
Health Sciences
Cale Zavitz

Diabetes  Diabetes is both a symptom and a disease o The symptom diabetes refers to the large amount of urine produced (polyuria) o The disease diabetes occurs when there are problems with the body’s regulation of serum glucose levels or antidiuretic hormone (ADH) levels both of which are characterized by polyuria- problem can be in pancreas (most unlovely organ in the body, according to Dr. Wainman) and in pituitary (elf boot)  Diabetes is the most common endocrine dysfunction, and the fourth leading cause of death by disease in North America Types of Diabetes  Diabetes has been recognized to exist in two main forms since the times of the Greeks (the ancient ones, I’m assuming, as there are still Greeks around) o Diabetes Mellitus  Roughly translates to “lots of sweet urine” (Mmm…)  Sometimes called “sugar diabetes”  Urine is sweet because there is lots of sugar in it (Ah!)- should never be excreting sugar because we can use it for lots of things- walking around, taking notes, lecturing (to name a few)  There is lots of urine because the dissolved sugar in the urine draws water into the urine by osmosis- sugary urine is excreted in large quantities- would attract ants o Diabetes Insipidus  Roughly translates to “lots of tasteless urine”  Has nothing to do with sugar- a hormone is not working- ADH- anti- diuretic hormone from the posterior pituitary (which makes one other hormone- oxytocin)- keeps you from peeing- if you don’t produce it, you pee like a race horse  ADH works to concentrate the urine  ADH is produced like oxytocin- produced in the hypothalamus and released in the posterior pituitary Diabetes Insipidus  The common cause for this disease is a decrease or blockade of the secretion of antidiuretic hormone (ADH)- this is called central diabetes insipidus because it happens in the central nervous system o This may be due to trauma to the infundibulum (stalk connecting the pituitary to the hypothalamus)- Would have to be hit pretty hard- but when brain moves, pituitary remains in Turk’s saddle- can cause damage o Pituitary tumours (adenomas- glandular tumours), or the surgery on tumours, as well as infection of the pituitary and hypothalamus can also lead to damage  Without the ADH, less water is resorbed from the filtrate back into the blood  Poor water reabsorption results in increased urine flow  The treatment is ADH- can be supplied in a nose spray- hormone absorbed through nasal mucosa- oxytocin can also be administered this way- parents would sometimes give this to kids to stop them from wetting the bed (e.g. for a sleepover party) ( News you can use)  A less common cause of DI is nephrogenic DI (nephrons are in kidney) o This disease results from the kidney becoming insensitive to ADH (produced in hypothalamus, released in posterior pituitary) o Damage is often secondary to drug use, e.g. lithium (mood stabilizer), demeclocycline, amphotericin B (antibiotics) o With ADH, will produce about 30 L of urine/day o The treatment is to consume adequate amounts of fluid to avoid dehydration and alterations in electrolyte levels- will give them electrolytes and ADH, as well Normal Regulation of Blood Glucose  Normal blood glucose is about 4.5 mmol/L (SI units)  If sugar levels go up: o Stimulus: high glucose in blood o Sensor & control center: Pancreas o Response: Insulin release o Effectors: certain body cells and the liver take up glucose and convert it to fat, amino acids, or glycogen o Response: glucose is lowered ADH Regulation  High blood osmotic pressure (such as when you are dehydrated) stimulates neurosecretory cells in the supraoptic nucleus of the hypothalamus to release ADH in the posterior pituitary  ADH leaves the pituitary and travels to the kidney where it causes the kidney to reabsorb water from the filtrate. It also increases blood pressure and inhibits sweating Anatomy of the Pancreas  Sugar regulation occurs in the pancreas  Head of pancreas sits nuzzled (or, if you prefer, “nizzled”) in the duodenum  Tail sits next to spleen  Sits against abdominal aorta- massive blood vessel along back  Interesting blood supply: o Splenic artery- goes to spleen- vessels from splenic artery provide blood to pancreas o Pancreaticoduodenal artery- some comes off of common hepatic (which also supplies the liver) and some comes off of the superior mesenteric artery- Head of pancreas receives blood from two of the biggest vessels of the abdominal aorta- from celiac (which gives off common hepatic) and from the superior mesenteric- these two high pressure arteries meet and form an anastomosis- if one is blocked, the other can still supply blood- you would die otherwise- cannot live without regulating sugar levels Microanatomy of the Pancreas  Exocrine acinus: about 99% of the volume of the pancreas consists of exocrine acini- they secrete 1200-1500 ml (which is a lot) of pancreatic “juice” per day. The fluid contains digestive enzymes and bicarbonate to buffer the gastric juice- neutralizes acidity from stomach- small intestine would be eroded otherwise  Endocrine part: o Beta cells: secrete insulin when blood glucose is high and when there is parasympathetic stimulation o Alpha cells: secrete glucagon when blood glucose is low but also when there is sympathetic stimulation. Glucagon leads to glucose production in the liver. Larger than Beta cells. Insulin  Insulin is a polypeptide released by the beta cells of the pancreas in response to low blood sugar. It is water soluble and has a cell surface receptor that has intrinsic tyrosine kinase activity  Under influence of insulin, effectors: o Accelerate facilitated diffusion of glucose into cells- if this does not happen, cells starve to death- glucose on outside does not help, must get inside cells- water follows glucose o Speed the conversion of glucose into glycogen- exerts less osmotic pressure, does not bring water into cell like glucose o Speed the synthesis of fatty acids- cannot store all that glycogen, make some into fat o Speed the synthesis of proteins from amino acids o Slow glycogen breakdown into glucose (glycogenolysis)  All of these processes lower the blood glucose levels and thus will ultimately inhibit insulin release- classic negative feedback regulation of glucose homeostasis Diabetes Mellitus  Sugar in blood is what ends up in urine, which drags out the water, resulting in polyuria  There are two types of diabetes mellitus: o In both types, blood sugar stays high (hyperglycemia) after meals, sugar is spilled into the urine (glycosuria) and a lot of urine is produced o Insulin dependent diabetes mellitus (IDDM or Type 1)  This type of diabetes is a result of inadequate production of insulin- if you do not make enough insulin, then you cannot activate tyrosine kinases, cannot take up glucose- disastrous  Occurs in pancreas- beta cells (responsible for insulin production) do not work- either make no insulin or not enough  Type 1 diabetes is treated with injections of insulin which decrease blood sugar- must monitor blood levels for rest of life  This disease usually occurs in young adults so it is sometimes called “juvenile onset diabetes”  The beta cells seem to be ruined by an autoimmune response of some sort- immune system destroys them Noninsulin Dependent Diabetes Mellitus (NIDDM or Type 2)  Result of inadequate response to insulin- plenty of insulin, but t
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