Lecture 7 Endo Module - Pancreas

Insulin leads to an increase in membrane _____ in muscle and fat. What happens if insulin is absent?

*GLUT 4 molecules* Insulin receptors are present in SM, liver, and fat In fat and SM, it promotes glucose uptake In the absence of insulin, these transport proteins are normally recycled slowly between the cell membrane and cell interior. Insulin triggers the rapid movement of a pool of glucose transporter vesicles to the cell membrane, where they fuse and expose the glucose transporters to the extracellular fluid. The transporters then move glucose by facilitated diffusion into the cell interior

What are the differences in symptoms between hyperglycemia and hypoglycemia?

*hypoglycemia:* -nervous, shakey -dizzy, confused -HA -hunger -cold clammy skin -fast HR -irritability *hyperglycemia:* -weak, tired -frequent urination -increased thirst -decreased appetite -blurry vision -itchy, dry skin -breath smells fruity

CV problems with DM-TII

-damages blood vessels

What major laboratory findings might you see in a patient with DKA?

-high blood glucose -high K+ -low arterial pH -positive serum ketones -high anion gap

The patient is an 18-year old college student who was brought by his fellow student to the ER room at Union Hospital. The patient had left suddenly after a birthday party around 4pm to go to his dorm. When the friend checked up on him at 6pm, he found him drowsy and confused. It is now 6.15pm. The patient is conscious. What is the most likely diagnosis?

-late onset type I diabetes -hyperglycemia, DKA

What are the different types of DM treatment?

1. DPP-4 inhibitors 2. GLP-1 receptor agonists 3. SGLT2 inhibitors --> newest drugs 4. insulin therapy 5. bariatric surgery

Fill in the blank: 1. BUN/Cr (16/1)are a little high --> think_____ 2. K+ is high because _______ 3. Diabetes(hi glucose) is an _____ diuretic 4. Na+ become _____ 5. HCO3- is low because Pt is _____, he is blowing off ____, and the 6. compensation in the kidney is to make the HCO3- go ____ 7. If something is slightly out of range, hydrate the person and ______ 8. Anion gap: _____ bodies contribute

1. protein breakdown 2. insulin normally drives K+ into the cell, but isn't --> stays in the blood 3. osmotic 4. low (hyponatremia) 5. acidotic; CO2 6. down 7. resample 8. ketone

What four things should you do to treat a patient in DKA?

1. start IV fluids ( 1L of 0.9% NaCl/hr initially) 2. insulin 3. K+ 4. HCO3-

What is diabetes mellitus?

Blood glucose > Diabetes mellitus is derived from the Greek word diabetes meaning siphon - to pass through and the Latin word mellitus meaning honeyed or sweet. This is because in diabetes excess sugar is found in blood as well as the urine. Manifestations of diabetes mellitus > excessive urination, thirst -Excessive blood glucose draws water into the urine > eliminates an abnormally large quantity of sweet urine - Body becomes dehydrated --> continually thirsty may also experience persistent hunger because the body cells are unable to --> access the blood glucose

How does insulin and glucagon regulate blood glucose levels?

Blood glucose concentration is tightly maintained between 70 mg/dL and 110 mg/dL. If blood glucose concentration rises above this range, insulin is released, which stimulates body cells to remove glucose from the blood. If blood glucose concentration drops below this range, glucagon is released, which stimulates body cells to release glucose into the blood Regulation of Blood Glucose Levels by Insulin and Glucagon Glucose -required for cellular respiration preferred cellular fuel glucose > breakdown of the carbohydrates -stored by the liver, muscles as glycogen converted to triglycerides > stored in adipose tissue pancreatic cells secrete glucagon or insulin to maintain normal levels

What panel do you want to order for a diabetic patient?

CMP

After DKA is resolved, K+ is given. Why?

Despite the fact that serum K" is most likely high, TOTAL BODY STORES are always depleted 1.) Osmotic diuresis (higher urine flow) 2.) K+ buffers negatively charged ketone bodes in urine 3.) Volume depletion Aldosterone increases K+ excretion Titratable acid Minimum 48 hours Ammoniagenesis takes hours to days

neuropathies with DM-TII

Distal loss of cutaneous sensation including temperature, touch and pain Decreased conduction velocity, demyelization and loss of nerve fibers Autonomic neuropathies include problems in the cardiovascular, gastrointestinal and genitourinary systems impotence, GI dysfunctions, lack of sweating, dry cracking skin

Why is foot care extremely important for people with diabetes mellitus?

Excessive blood glucose levels damage the blood vessels and nerves of the body's extremities, increasing the risk for injury, infection, and tissue death. Loss of sensation to the feet means that a diabetic patient will not be able to feel foot trauma, such as from ill-fitting shoes. Even minor injuries commonly lead to infection, which can progress to tissue death without proper care, requiring amputation

What is the polypol pathway?

Glucose is converted to sorbitol, a sugar that accumulates in tissues glucose = sticky --> sticks to everything

management of DM-TII

Healthy eating Regular exercise Possibly, diabetes medication or insulin therapy Blood sugar monitoring These steps will help keep your blood sugar level closer to normal, which can delay or prevent complications. Healthy eating Contrary to popular perception, there's no specific diabetes diet. However, it's important to center your diet on these high-fiber, low-fat foods: Fruits Vegetables Whole grains You'll also need to eat fewer animal products, refined carbohydrates and sweets. Low glycemic index foods also may be helpful. The glycemic index is a measure of how quickly a food causes a rise in your blood sugar. Foods with a high glycemic index raise your blood sugar quickly. Low glycemic index foods may help you achieve a more stable blood sugar. Foods with a low glycemic index typically are foods that are higher in fiber. A registered dietitian can help you put together a meal plan that fits your health goals, food preferences and lifestyle. He or she can also teach you how to monitor your carbohydrate intake and let you know about how many carbohydrates you need to eat with your meals and snacks to keep your blood sugar levels more stable

Ansler chart

How to use: Wear the eyeglasses you normally wear when reading. Position the chart 14 inches away from your face. Cover one eye at a time with your hand. Stare at the dot in the center. Do not let your eye drift from the center dot. Contact your eye doctor immediately if any of the straight lines appear wavy or bent, any of the boxes differ in size or shape from the others, or any of the lines are missing, blurry or discolored.

The patient is an 18-year old college student who was brought by his fellow student to the ER room at Union Hospital. The patient had left suddenly after a birthday party around 4pm to go to his dorm. When the friend checked up on him at 6pm, he found him drowsy and confused. It is now 6.15pm. The patient is conscious. What would you look for as part of the Physical if suspicious of Type I Diabetes?

Hyperglycemia > 250mg/dl Signs of acidosis Breathing pattern Acidosis with blood pH < 7.3 Serum bicarbonate <15mEq/L Serum + for Ketones (tells insulin is very low, wouldn't make ketones if had insulin)

What are the acute symptoms of type II diabetes?

Hyperglycemic Hyperosmolar Non-Ketotic Syndrome (HHNS) Not associated with ketones in the blood Occurs when patients are ill or stressed Insufficient fuel supply lethargy Increased plasma osmolarity thirst Excess glucose (hyperglycemia often >600mg/dl) exceeds renal capacity and causes osmotic diuresis frequent urination, bed wetting Additional possible gastrointestinal losses due to vomiting or diarrhea severe dehydration, hypotension, cardiovascular problems Frequent urination, drowsiness, lethargy and thirst. Can cause coma and death BIGGEST difference is no ketones in DMII

What K+ status do you expect for type I diabetes?

Hyperkalemic (no insulin, acidosis) Hypokalemia (insulin therapy, diuresis) Normokalemia at the time of measurement

What do we give D5/0.45 NS for DKA?

Hypertonic Hyperglycemia shifts water from ICF to ECF can lead to hyponatremia Augmented by osmotic diuresis good way to add particles to help maintain ICF osmolarity

The patient is an 18-year old college student who was brought by his fellow student to the ER room at Union Hospital. The patient had left suddenly after a birthday party around 4pm to go to his dorm. When the friend checked up on him at 6pm, he found him drowsy and confused. It is now 6.15pm. The patient is conscious. What would you look for as signs of this patient having Type I Diabetes?

Increased thirst Increased urination Fatigue Weight loss Increased appetite Look for Kussmaul breathing for signs of acidosis Will need to get arterial blood gas Also, smell their breath fruity - ketones

Why do we add glucose to the insulin infusion?

Insulin NEEDS to be given to make the liver stop producing ketones! To avoid hypoglycemic coma ("insulin shock") glucose is given.

What are parts of a Diabetic Consultation?

Lifetime insulin therapy Blood glucose monitoring Home monitoring of ketones Self-care: sickness, exercise, stress, alcohol Flu shots, vaccinations Guidelines when to seek medical attention Regular follow-ups Yearly eye-exam Innovations? Smart pumps, artificial pancreas, etc

What are the long-term complications of type II diabetes?

Mechanism > Glycation Non-enzymatic attachment of glucose to amino groups in proteins such as proteoglycans, collagen, elastin, LDL and DNA alters microvasculature and flexibility of RBCs Advanced Glycation Endproducts every single person will have vascular issues

What is type II diabetes?

Obesity leads to insulin receptor signaling problems Obesity leads to less insulin receptors and less responsive receptors

c-peptide

Pancreatic beta-cells produce proinsulin, which splits into C-peptide and insulin and are both released into circulation in a 1:1 ratio C peptide Used clinically to differentiate between Type I and II diabetes Type I levels: absent or low Type II levels: normal or increased C peptide useful to determine the status of the type diabetic C peptide : Still considered to be biologically inactive However, diabetics who receive insulin and C peptide have less side effects C peptide signaling leads to stimulation/ upregulation of eNOS and Na/K/ATPase C peptide has much longer half-life than insulin Overall these observations raise the possibility that C-peptide may serve as a potential therapeutic agent for the treatment or prevention of long-term complications associated with diabetes

How does the kidney regulate acid?

Regulate HCO3- (fast) If there is a lot of acid, it makes a lot of ammonium to get rid of acid (takes a long time)

Nephronpathies with DM-TII

Stress due to advanced glycosylation end products and cytokines Glomerulosclerosis due to basement membrane thickening Hyperglycemia causes hyperfiltration and renal injury Hypertension stresses kidneys

What would be the physiological consequence of a disease that destroyed the beta cells of the pancreas?

The beta cells produce the hormone insulin, which is important in the regulation of blood glucose levels. All insulin-dependent cells of the body require insulin in order to take up glucose from the bloodstream. Destruction of the beta cells would result in an inability to produce and secrete insulin, leading to abnormally high blood glucose levels and the disease called type 1 diabetes mellitus

What are the two main forms of diabetes?

There are two main forms of diabetes mellitus. 1. Type 1 Insulin Dependent: diabetes is an autoimmune disease affecting the beta cells of the pancreas. -beta cells do not produce insulin - genetic susceptibility. -synthetic insulin needed --> ~5% of all diabetes cases 2. Type II Non insulin dependent diabetes -caused by down-regulation of insulin receptors in target tissues, insulin resistance -Insulin is secreted but at normal concentrations, it cannot activate its receptors on muscle, liver, and adipose tissue -insulin unable to produce its usual metabolic effects --> 95% of cases in USA

The patient is an 18-year old college student who was brought by his fellow student to the ER room at Union Hospital. The patient had left suddenly after a birthday party around 4pm to go to his dorm. When the friend checked up on him at 6pm, he found him drowsy and confused. It is now 6.15pm. The patient is conscious. He is admitted to the ICU. What is the proper course of treatment?

Two venous cannulas: One for fluid, electrolyte, insulin The second one for regular glucose sampling Insulin IV Monitor glucose every 15 minutes, then every hour Keep serum glucose between 150-200mg/dL Tylenol (fever) Broadband antibiotic with 0.9% NaCl DKA--> think fluid and insulin

What is the level of C peptide in: a. type I diabetes? b. type II diabetes?

a. absent/decreased b. normal/increased *C peptide helps to distinguish between types I and II DM *can help tell if pt is making insulin

What molecule does insulin act on?

effects K+ -Stimulates uptake of K+, PO3 and Mg2+ into muscle cells (linked to glycogen synthesis, protein synthesis and Na/K-ATPase activity) Stimulates reabsorption of electrolytes by renal tubules Insulin is used to treat acute, life-threatening hyperkalemia. Give insulin as insulin drives potassium into cells.

The patient is an 18-year old college student who was brought by his fellow student to the ER room at Union Hospital. The patient had left suddenly after a birthday party around 4pm to go to his dorm. When the friend checked up on him at 6pm, he found him drowsy and confused. It is now 6.15pm. The patient is conscious. How serious is this condition?

extremely --> patient admitted to ICU

What is the goal blood glucose in a patient with DKA?

get the glucose to 225-250 mg/dL

If an autoimmune disorder targets the alpha cells, production of which hormone would be directly affected? A. somatostatin B. pancreatic polypeptide C. insulin D. glucagon

glucagon

The #1 trigger of an episode of a type 1 diabetic is due to what?

infection or trauma to the body

Why are infants who are born to mothers with diabetes often larger than other babies?

insulin and IGF-1 share IRS-1 signaling mechanisms -baby gets more glucose than needed --> extra glucose is stored as fat -baby makes extra insulin that acts as "growth factor"

Which of the following statements about insulin is true? A. insulin acts as a transport protein, carrying glucose across the cell membrane B. insulin facilitates the movement of intracellular glucose transporters to the cell membrane C. insulin stimulates the breakdown of stored glycogen into glucose D. insulin stimulates the kidneys to reabsorb glucose into the bloodstream

insulin facilitates the movement of intracellular glucose transporters to the cell membrane

What major nutrient does glucagon create that is a major contributor to diabetic ketoacidosis?

ketoacids

How is insulin receptor signaling measured?

measure glucose uptake