2 main types of pancreatic tissues

Acini

Islets of Langerhans

What do acini do? 

What do the Islets of Langerhans do?

secrete digestive juices into duodenum 

secrete hormones into the bloodstream

Alpha cells -secrete glucagon

(located around periphery, ~ 20% of islets)

Beta cells -secrete insulin

 (in center, ~80%)

Delta cells -secrete somotostatin

(scattered throughout)

What is the other name for somatostatin?

Where else in the body is somatostatin released from?

growth hormone inhibiting hormone

- from GI tract

-hypothalamus

(stored in the anterior pituitary)

Insulin is a small ____ comprised of __ amino acid chains linked to each other by 2 ______

How long does insulin circulate in plasma unbound?

Binds to receptors on ________

Insulin is a small protein comprised of 2 amino acid chains linked to each other by 2 disulfide bridges

10-15min (the pancreas secretes a basal rate of insulin every 10-15min)

Binds to receptors on target cell membrane

How many subunits does the insulin receptor consist of? Where are they each located?

4 subunits:

2 alpha subunits lie outside the cell membrane

2 beta subunits penetrate the membrane

Where does insulin bind to on the insulin receptor?

What activates the beta subunits of the insulin receptor?

What do the activated beta subunits then act as?

What does this do?

alpha subunits

binding of insulin to the alpha subunits activates beta subunits

activated beta subunits then act as an enzyme (a local tryosine kinase)

phosphorylates additional enzymes

1. Glucose transporter

(normally lives inside the cell until activated by tyrosine kinase and then it goes to cell membrane to let glucose in)

2. Protein synthesis

3. Fat synthesis

4. Glucose synthesis

5. Growth & gene expression

Insulin is an anabolic or catabolic hormone?

Where in the body does it stimulates uptake, storage, and use of glucose?

It increases cellular permeablility for what 3 things?

Insulin is an anabolic hormone

80% of cells, esp. mm, adipose tissue, & liver

amino acids, potassium, phosphate ions

(as glucose permeability incr, so does K+ & phospate permeability)

Is insulin needed for glucose transport into resting or active mm?

What happens to glucose that is not needed for energy in the muscle?

resting only (exercising mm can take up glucose without insulin)

excess glucose stored as glycogen

Insulin stimulates transport of amino acids into the muscle cells & promotes protein synthesis.

     Is insulin required for uptake of glucose into the liver?

What does insulin stimulate in the liver?

No

stimulates hepatic processing of glucose

    What 2 things does insulin promote in the liver?

What 2 things does insulin inhibit in the liver?

promotes storage of glucose as glycogen

promotes conversion of excess glucose into FFA 

inhibits breakdown of liver glycogen into glucose

inhibits gluconeogenesis

(insulin stimulates anabolic processes & inhibits catabolic processes)

 the liver then packages these fatty acids into VLDL & triglyderides & transports them to adipose tissue

(again a storage and anabolic function)

Insulin promotes fat ___ & ___ by adipose cells

Insulin inhibits which hormone to prevent the breakdown of fats in adipose cells?

Insulin promotes fat synthesis & storage by adipose cells

Insulin inhibits hormone sensitive lipase inside fat cells

Actions of insulin on Protein metabolism & growth

Insulin promotes protein ____ & _____.

Stimulates transport of ______ into the cell.

Increases the translation of ___, thus forming new proteins.

Inhibits protein _____.

Depresses ________ in the liver.

Insulin promotes protein synthesis & storage.

Stimulates transport of amino acids into the cell.

Incr. the translation of mRNA, thus forming new proteins.

Inhibits protein catabolism.

Depresses gluconeogenesis in the liver.

*Insulin functions synergistically with ___ hormone?

growth hormone

 (both insulin & growth hormone needed for growth to occur; on their own will not have much of an effect)

Incr blood glucose

incr blood free fatty acids

incr blood amino acids

GI hormones(gastrin, cholecystokinin, secretin, gastric inhibitory peptide)

Glucagon, growth hormone, cortisol(Counter-regulatory hormones)

Parasympathetic stimulation: Ach

Insulin resistance; obesity

Sulfonylurea drugs (glyburide, tolbutamide)

Decr blood glucose

Fasting

Somatostatin (GHIH)

alpha-agonists

Functions of glucagon

It is a catabolic or anabolic hormone?

Stimulates what 2 things in the liver?

It is a catabolic hormone

glycogenolysis  and gluconeogenesis

*Insulin & glucagon function as a ___ unit.

They function ______ at every level.

* Insulin & glucagon function as a bihormonal unit.

They function antagonistically at every level.

What do insulin & glucagon do together? (2)

Name 3 main tissues sensitive to insulin & glucagon

-they maintain nutrient availability to tissues which are

 sensitive to these hormones

-they also maintain a relatively constant blood

 concentration of glucose for the brain (an insulin independent tissue)

mm, adipose tissue, and liver

*What are the 2 cell types that make up the bihormonal unit to secrete glucagon and insulin?

alpha & beta cells

What are 3 anabolic processes?

Is insulin increased or decreased for these to occur?

Is glucagon increased or decreased for these to occur?

Lipid synthesis

protein synthesis

glycogen synthesis

incr insulin

decr glucagon

What are 6 catabolic processes?

Is insulin increased or decreased  for these to occur?

Is glucagon increased or decreased for these to occur?

lipolysis

fatty acid oxidation

ketogenesis

glycogenolysis

proteolysis

gluconeogenesis

decr insulin

incr glucagon

Insulin-Glucagon Ratio

 What happens following a meal?

Is the net effect anabolic or catabolic?

Blood glucose incr, stimulating insulin & inhibiting glucagon

This results in anabolic processes & prevents further incr in glucose (in the blood)

Insulin-Glucagon Ratio

What happens following fasting or exercise?

Is the net effect anabolic or catabolic?

The alpha-beta unit detects fall in glucose, resulting in a decr in insulin secretion & an incr in glucagon secretion.

The net effect is catabolic, thus maintaining critical blood glucose levels

In poorly treated or untreated DM, plasma levels of glucagon are often markedly increased. Why does glucagon secretion occur?

Alpha cells think they're starving b/c glucose not getting into cells (alpha cells insulin dep.), so they secrete glucagon

makes the problem worse (incr blood glucose even more)

T/F glucose is essentially the only fuel the brain can use?

How much glucose does the brain use per hour?

Glucose concn is kept w/in very narrow limits, normally varying only about __%

True

4 gm/hr

Glucose concn is kept w/in very narrow limits, normally varying only about 50%

Type I: IDDM

insulin deficiency is __ or ___

Pancreas & plasma contain __ or __ insulin

Requires ____ therapy

Prone to _____

Associated w/ _____ antibodies

Genetic component on chromosome _ may be partly responsible for susceptibility. Genetic link is ___.

Accounts for ___% of all DM.

Begins before age ___, usually around ___, but has been diagnosed in utero.

Usually begins abruptly in a ____ child, often following an infection.

T/F: This type of DM is easy to control

insulin deficiency is severe or absolute

Pancreas & plasma contain little or no insulin

Requires insulin therapy

Prone to DKA

Associated w/ anti-islet cell antibodies

Genetic component on chromosome 6 may be partly responsible for susceptibility. Genetic link is weak

Accounts for 10% of all DM.

Begins before age 40, usually around puberty, but has been diagnosed in utero.

Usually begins abruptly in a slender child, often following an infection. (could be what triggers autoimmune response)

FALSE:

labile & difficult to control

Type II: NIDDM

__ insulin deficiency. Circulating insulin levels may be ...?

Pancreas contains ____ insulin

Often controlled by _______

Clinical course more ____

Accounts for __% of all DM.

Begins insidiously usually in an ____ person over the age of 40, although is occurring more frequently in children now.

T/F: Insulin withdrawal always causes DKA

Relative insulin deficiency. Circulating insulin levels may be low, normal, or high.

Pancreas contains considerable insulin

Often controlled by diet and/or oral hypoglycemic agents

Clinical course more stable

Accounts for 90% of all DM.

Begins insidiously usually in an obese person over the age of 40, although is occurring more frequently in children now.

FALSE: usually does NOT cause DKA

Gestational diabetes occurs in 2-3% of pregnancies.

Presents as glucose intolerance w/ usual onset at ___ wks.

Does glucose tolerance correct after delivery?

Gestational diabetes occurs in 2-3% of pregnancies.

Presents as glucose intolerance w/ onset at 24-30 wks.

usually

What is the etiology of secondary diabetes?

What are 4 things that can cause this?

secondary to pancreatic insult or excessive demand

pancreatic disease

drugs (glucocorticoids)

acromegaly

cushing's disease

Is there a stronger hereditary link in Type I or Type II DM?

Type I has been associated w/ certain ___ antigens & is an ____ process

Type II has no strong autoimmune basis & is usually precipitated by _____

Insulin mediated stimulation of __ ___ is impaired in NIDDM

stronger genetic link in Type II

Type I has been associated w/ certain HLA antigens & is an autoimmune process

Type II has no strong autoimmune basis & is usually precipitated by obesity

Insulin mediated stimulation of tyrosine kinase is impaired in NIDDM

Pathophysiology of DM

Insulin deficiency decreases glucose uptake in mm and fat cells. As glucose entry into cells diminishes, ____ is released from the _____ = more hyperglycemia.

As glucose entry into cells diminishes, glycogen is released from the liver

Pathophysiology of Diabetes

What BS level exceeds the kidney's ability to reabsorb glucose & thus glucose is found in the urine (sweet urine)

What systemic effects result?

As BS approaches 180, the capacity of the renal tubules to reabsorb glucose is exceeded, so glucose is excreted into urine.

Urine glucose acts as an osmotic diuretic, resulting in excretion of water & salts in the urine. Cellular dehydration occurs.

The decreased insulin/glucagon ratio also stimulates lipolysis & protein catabolism. The increased lipolysis results in the formation of ___, which results in what metabolic state?

Increased lipolysis results in the formation of ketoacids, which results in metabolic acidosis.

impaired wound healing

hyperosmolarity

osmotic diuresis

impaired phagocyte fcn

electrolyte disturbances

I HOPE

When in the day should we schedule surgery for DM pts?

When should we d/c hypoglycemic agents

early in the day to limit duration of fasting

evening before Sx

T/F: it is ok to proceed w/ elective surgery if pt has hyperglycemia, electrolyte imbalance, or ketoacidosis.

FALSE!!

Do not proceed w/ elective surgery under these circumstances

if pt has life-threatening infection, it is ok to proceed w/ surgery even if BS>200--surgery may be the definitive treatment for the infection & should not be cancelled b/c of high glucose levels --- BUT no sx with ketoacidosis -- must hydrate first per lec!

T/F As part of the preop eval of a DM pt, we need to evaluate for limited joint mobility (prayer sign) & limited neck extension as potential for difficult airway.

risk of aspiration on induction

introp CV lability 

The HbA1C evaluates avg blood glucose levels from the past ___ days? What is the target level for HbA1C?

120 days

 <7%

1. resting tachycardia
2. orthostatic hypotension
3. absent beat-beat variation w/deep breathing
4. cardiac dysrhythmias (QT abnormalities)
5. sudden death syndrome
6. gastroparesis--vomiting, diarrhea, abd distension
7. bladder atony
8. impotence
9. asymptomatic hypoglycemia

IDDM pts undergoing major surgery should be treated w/insulin.

Which route of admin is better: SQ or IV? why?

If a pt has an insulin infusion pump, how should it be set?

IV route more reliable, but requires close monitoring - check every 1-2hrs at least---hypothermia & vasoconstriction may interfere w/ SQ absorption

leave on basal rate of infusion pump and check sugars throughout case.

How do the stress of anesthesia & surgery affect insulin requirements?

T/F: Type I diabetics are much more sensitive to insulin, and will require smaller doses to control glucose?

increase insulin requirements d/t incr catecholamines & cortisol = inc BS.

True

Do you need to utilize RSI and use a cuffed tube with DM pts that have gastroparesis or autonomic neuropathy?

Why might hyperglycemia occur in diabetic pt in OR?

How do IAs affect insulin release?

ABSOLUTELY

d/t increases in plasma catecholamines & cortisol

IAs may impair release of insulin in response to glucose

Epidural & spinal anesthesia preserve glucose tolerance presumably owing to inhibition of the catecholamine response to surgery

GA depress insulin release in response to inc BS

What can cardiac autonomic neuropathy result in?

What may be the most effective drug therapy in these cases?

Bradycardia & hypotension that develop suddenly & are unresponsive to IV admin of atropine and/or ephedrine

epi=most effective

What is the most critical step in management of IDDM pt periop?

check glucose levels frequently

check q 1-2 hrs before, during, & after surgery until pt fully awake & alert

What is the treatment of hypoglycemia?

<60

60>BS<120

How many gm of glucose in 100ml D5W?

Admin D50W for glucose <60

Admin D5W for glucose levels 60>BS<120

D5W 100ml = 5 gm glucose

(remember brain uses 4gm/h)

HbA1C:% = avg BS level

5% = 

6% = 

7% = 

8% = 

9% = 

10% =