Endo 3

Question 1

Is diabetes a symptom or disease?

Answer 1

• both
• symptom: large amount of urine produced (polyuria)
• disease occurs becuase of hyperglycemia or not enough ADH both of which are characterized by polyuria
• most common endocrine dysfunction!

Question 2

What is diabetes mellitus?

Answer 2

• “lots of sweet urine”
• sometimes called sugar diabetes
• lots of sugar in the urine (these glucose should be taken back into the blood to be used but it is instead getting out in the urine)
• lots of urine because the glucose will pull water with it into the urine by osmosis

Question 3

What is diabetes insipidus?

Answer 3

• “tasteless urine”
• disease of where there is a lack thereof or a lack of responsiveness to ADH
• ADH works to concentrate the urine (diuresis is peeing, ADH keeps you from making a lot of urine)

Question 4

What is the common cause for diabetes insipidus?

Answer 4

• decrease or blockade of the secretion of ADH which is called central diabetes insipidus because it happens in the CNS
• may be due to trauma to the stalk connecting the pituitary to the hypothalamus (infundibulum)
• pituitary tumours or surgery on the tumours as well as infection of pituitary and hypothalamus can lead to damage

Question 5

What is the treatment for diabetes insipidus?

Answer 5

• without ADH water is not as well reabsorbed resulting in increased urine flow
• ADH nasal spray

Question 6

What is the uncommon cause of diabetes insipidus? How is it treated?

Answer 6

• nephrogenic DI
• kidney becomes insensitive to the ADH
• damage is often secondary to drug use (lithium, demeclocycline, amphotericin B)
• treatment is to consume adequate amounts of fluid to avoid dehydration and alterations in electrolyte levels (try to also give them ADH and electrolytes)

Question 7

Describe normal regulation of blood glucose levels

Answer 7

• normal BG level is 4.5mmol/L
• BG rises (stimulus)
• pancreas is detector and control centre
• response and release: insulin
• insulin causes effectors to take up glucose

Question 8

How is ADH stimulated?

Answer 8

• high blood osmotic pressure (such as when you are dehydrated) stimulates neurosecretory cells in the supraoptic nucleus of hypothalamus to release ADH in the posterior pituitary
• ADH leaves the pituitary and travels to kidney where it causes the kidney to reabsorb water from the filtrate while also increasing blood pressure and inhibiting sweating

Question 9

Describe the blood supply to the pancreas

Answer 9

• pancreas sits near abdominal aorta
• splenic artery provides blood to pancreas (these create anastomosis with some vessels off of the inferior mesenteric artery)
• pancreaticoduodenal comes off common hepatic
• superior mesenteric artery
• head of pancreas gets blood from celiac which gives off common hepatic and superior mesenteric then creates an anastomosis

Question 10

What is the function of the exocrine acinus?

Answer 10

• 99% of pancreas volume consists of this which secrete 1.2-1.5L of bicarbonate fluid per day
• contains digestive enzymes and bicarbonate that buffer the gastric juice

Question 11

What makes up the endocrine part of the pancreas?

Answer 11

• islet of Langerhans
• beta cells: secrete insulin when blood glucose is high and when there is parasympathetic stimulation
• alpha cells: secrete glucagon when blood glucose is low but also when there is sympathetic stimulation- glucagon leads to glucose production in the liver (a bit larger than beta cells and stain darker)

Question 12

What is insulin? What do the effectors do under the influence of insulin?

Answer 12

• polypeptide released by beta cells of pancreas
• water soluble and has cell surface receptor with intrinsic tyrosine kinase activity
• accelerate facilitated diffusion of glucose into the cells (glucose brings water so cells will fill with water), speed conversion of glucose into glycogen (glycogen doesn’t exert much osmotic pressure), speed synthesis of fatty acids, speed synthesis of proteins from amino acids, slow glycogen breakdown into glucose (glycogenolysis)
• all of these lower blood glucose and ultimately inhibit insulin release

Question 13

What are the 2 types of diabetes mellitus?

Answer 13

-in both types, BG stays high (hyperglycemia) after meals, sugar is spilled into urine (glycosuria), and lots of urine is produced (polyuria)

Insulin dependent diabetes mellitus (IDDM) or Type 1: Inadequate insulin production- beta cells in pancreas don’t produce insulin at all or enough. Treated with insulin injection which decrease blood sugar. Usually occurs in young adults so called juvenile onset diabetes. Beta cells are ruined by some sort of autoimmune response.

Noninsulin dependent diabetes mellitus (NDDM) or Type 2: Inadequate response to insulin- resistant to the effects of insulin. Disease is associated with adulthood and is called adult-onset diabetes. Increases in body weight are important correlate in T2D and certain cultural groups are at risk suggesting genetic factors. T2D can also be treated with insulin but diet/exercise and antihyperglycemics (like metformin) are used. T2D is showing up in juvenile population because of childhood obesity increases (26% children aged 2-17 in Canada are overweight/obese, 60% adults are overweight and 23% are obese).

Question 14

What is the effect of a lack of insulin?

Answer 14

• cells starve to death and begin to burn fat in large quantities
• burning of fat leads to production of poorly metabolized fragments of fat called ketone bodies
• ketone bodies contain odorous molecules such as acetone so breath smells fruity, ketone bodies are also acidic so body’s pH falls- ketoacidosis
• fat begins to deposit on BV walls (retinas can become damaged and gangrene can occur in hands and feet); atherosclerosis, amputation
• loses weight and is constantly hungry
• person begins to starve to death
• insulin dependence occurs only in very severe T2D since most T2D have high adiposity

Question 15

How do diabetic foot ulcers develop?

Answer 15

• large amounts of lipid in the bloodstream and other problems caused by hyperglycemia lead to damage to the arterial walls and poor circulation
• areas which are predisposed to poor circulation and have friction will tend to ulcerate and may become infected

Question 16

How is blood sugar regulation changed in pregnancy?

Answer 16

• same regulatory systems in place to deal with blood sugar when you are pregnant and not pregnant
• fetus only receives glucose from maternal circulation but it deals with blood sugar in the same way as the adult
• fetus constantly takes sugar across placenta
• pregnant women tend to develop hypoglycemia between meals and during sleep (fetus continues to draw glucose during times of fasting)
• hormones produced during pregnancy cause the cells, which normally respond to insulin, to resist effects of insulin and not take up glucose; more pronounced in later stages of pregnancy when reproductive hormone levels are highest

Question 17

Why would placenta work to make body insulin resistant?

Answer 17

• if you are going to end up having glucose levels that are high enough for fetus overnight, it will try to prevent you from taking glucose out of bloodstream and into tissues
• fetus wants a lot of blood sugar around so it can grow so releases hormones to make mom insulin resistant
• glucose levels stay up in mom longer after they’ve eaten
• because mom is insulin resistant, she will make more insulin to try to fight but placenta wins and fetus gets enough sugar

Question 18

What is gestational diabetes mellitus (GDM)? What effects does this have on the infant?

Answer 18

• when diabetes occurs as a new disease in pregnancy
• abnormal maternal glucose regulation occurs in 3-10% of pregnancies
• 80% or more of this glucose intolerance occurs in patients with GDM
• infants experience double the risk of serious injury at birth, triple the likelihood of c-section delivery, and 4x incidence of NICU admission
• proportional to magnitude of maternal hyperglycemia
• can be screened for by oral glucose challenge test

Question 19

What happens with high maternal glucose?

Answer 19

• increased glucose in maternal circulation moves through the placenta to fetus and causes fetus to secrete large amounts of insulin; this can increase lipogenesis in baby, mom’s insulin can’t get to baby because placenta destroys the peptide
• high insulin and glucose stimulates release of insulin-like growth factors; baby becomes larger but not more developed (macrosomic)- increased maternal and neonatal death rates, primary c-section for cephalopelvic disproportion and for nonprogression of labour is 2x as frequent if infant has macrosomia, brachial plexus paralysis and clavicular fractures are more frequent in larger infants
• fetus will have to develop chronic hyperinsulinemia to deal with high sugar load

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Question 20

What were the results of the glucose screening programs for moms?

Answer 20

• hard to tell the two curves apart between normal and GDM
• altered glucose response is normal part of pregnancy that helps fetal growth
• mother’s normal response to glucose in the 3rd trimester looks a lot like T2D
• women who screen positive are likely to develop T2D later in life so perhaps GDM is the unmasking of latent T2D
• screening doesn’t seem to make any difference in outcomes of pregnancies
• perhaps GDM isn’t a disease at all
• women with T1D and T2D still need to be followed carefully