Pancreas Flashcards Preview

Endocrine > Pancreas > Flashcards

Flashcards in Pancreas Deck (60):

(Islets of Langerhans cell types)

All derived from pancreatic buds (embryologically)
- Alpha cells
- Beta cells
- Delta cells


Pancreatic Alpha cells

- 20% of the islet cells
- Secret glucagon
- Located at the periphery


Pancreatic Beta cells

- Major cell type
- Secret insulin (along with C peptide [long term marker])
- Located in the center
- Receive blood first


Pancreatic Delta cells

- 5% of islet cells
- Secrete somatostatin
- Interspersed throughout the pancreas



- It is a peptide hormone
- Works through tyrosine kinase
- Anabolic
- Released along with C peptide (its long term marker)


(Effects on Glucose metabolism)

- Increases glucose uptake by adipose tissue and skeletal muscles (GLUT-4)
- Increases glucose uptake by liver (by stimulating glucokinase)
- Decreases glucose breakdown
- Increases glucose storage


(Effects on Protein metabolism)

- Increases amino acids uptake
- Increases protein synthesis
- Decreases protein degradation


(Effects on Fat metabolism)

- Decreases hormone sensitive lipase activity
- Increases fatty acids uptake (by stimulating lipoprotein lipase)
- Increases triglycerides synthesis
- Increases acetyl CoA carboxylase enzyme activity


(Glucose storage mechanism)

Through stimulating the following enzymes (by dephosphorylation):
- Glucokinase
- Glycogen synthase
- PFK-1 (via PFK-2)
- Pyruvate kinase
- Acetyl CoA carboxylase


(Glucose release mechanism)

Through stimulating the following enzymes (by phosphorylation):
- Glycogen phosphatase
- Pyruvate carboxylase
- Fructose 1,6-bisphosphatase
- Glucose-6-phosphatase


(Secretion Stimuli)

- Glucose
- Amino acids like arginine
- Intestinal hormones:
* GIP (gastric inhibitory peptide or glucose-dependent insulinotropic peptide)
* GLP-1 (glucagon like peptide): Exenatide is its synthetic analog
- Glucagon
- Hyperkalemia
- Dipeptidyl peptidase-IV (DPP-IV) [breaks down GLP-1] inhibitors like Sitagliptin
- Drugs that block ATP-sensitive K+ channels like sulfonylureas


(Secretion Inhibitors)

- Somatostatin
- Sympathetic innervation and norepinephrine (alpha-2 receptors)
- Hypokalemia (like in hydrochlorothiazide)



- Glycogenolysis
- Gluconeogeneis
- Increases urea production
- Increases ketone bodies by inhibiting acetyl CoA carboxylase (though it is not the main regulator [insulin is])
- Increases lipolysis by stimulating hormone sensitive lipase
- Inotropic effect on the heart (cause it is working through Gs cAMP)


(Other Effects)

- Moves K+ into cells by stimulating Na+/K+ ATPase
- Increases Na+ retention (kidneys)
- Decreases glucagon release


(Secretion Stimuli)

- Hypoglycemia
- Amino acids like arginine


(Secretion Inhibitors)

- Hyperglycemia
- Insulin
- Somatostatin



- Preproinsulin synthesized in RER
- Then cleavage of presignal will produce proinsulin (insulin and C peptide) that is stored in secretory granules



- Increased metabolism of glucose in Beta cells will increase ATP production
- ATP will block the ATP sensitive K+ channels which results in generating an action potential (membrane depolarization)
- This depolarization will cause Ca++ entry into the cells which in turn causes cleavage of proinsulin and exocytosis of insulin and C peptide equally


Insulin-dependent glucose transports
(Names and Locations)

GLUT-4: in adipose tissue and striated muscles (exercise also increases their expression)


Insulin-independent glucose transports
(Names and Locations)

- GLUT-1: RBCs, brain, cornea and placenta (insulin does not cross the placenta)
- GLUT-2 (bidirectional): beta islet cells, liver, kidneys, and small intestine
- GLUT-3: brain and placenta
- GLUT-5 (fructose): spermatocytes and GI tract


(Hormonal Control)

- When it is low, glucagon will raise it
- When it is very low, epinephrine will release glucose from liver and GH will inhibit GLUT-4 mediated uptake of glucose by the adipose tissue and skeletal muscles
- When it remains very low, cortisol will release glucose from liver and also makes amino acids from skeletal muscles available to the liver for gluconeogenesis


Diabetes Mellitus Type 1 vs. Type 2
(Primary Cause, Insulin necessary for Rx, Age, Association with obesity)

- 1: autoimmune destruction of Beta cells (due to glutamic acid decarboxylase antibodies [type IV hypersensitivity]). 2: increase resistance to insulin (post-receptor alternation), progressive pancreatic beta-cells failure
- 1: Always. 2: Sometimes
- 1: < 30 years. 2: > 40 years
- 1: No. 2: Yes


Diabetes Mellitus Type 1 vs. Type 2
(Genetic predisposition, HLA system association, Glucose intolerance, Insulin sensitivity)

- 1: Relatively weak (50% concordance in identical twins), ploygenic. 2: Relatively strong (90% concordance in identical twins), ploygenic
- 1: Yes (HLA-DR3 and -DR4). 2: No
- 1: Severe. 2: Mild to moderate
- 1: High. 2: Low


Diabetes Mellitus Type 1 vs. Type 2
(Ketoacidosis, Beta-cell numbers, Serum insulin level, Classic symptoms [Presentation])

- 1: Common. 2: Rare
- 1: decreased (with islet lymphocytic infiltration [insulitis] and fibrosis). 2: variable (with islet amyloid polypeptide (IAPP) deposits)
- 1: Low. 2: variable
- 1: Common. 2: sometimes


Insulin Deficiency
(Metabolic Effects)

- Decreased tissue glucose uptake, Increased glycogenolysis and gluconeogenesis ---> hyperglycemia (increased plasma osmolarity and thirst) and glycosuria (osmotic diuresis, loss of water, Na+ and K+, hypovolemia, circulation failure and decreased tissue perfusion, coma/death)
- Increased proteolysis ---> decreased protein and weight loss ---> increased gluconeogenesis
- Increased lipolysis ---> increased plasma free fatty acids ---> Increased ketogenesis, ketonemia and ketonuria (vomiting) ---> Anion gap metabolic acidosis (hyperventilation)
* vomiting and hyperventilation both contribute to loss of water, Na+ and K+
* circulation failure and decreased tissue perfusion will lead to increase in serum lactate which will also contribute to the anion gap metabolic acidosis


Insulin Deficiency
(Effects on Na+ and K+)

- Na+:
* Losing body stores because of polyuria
* May see hypernatremia because of dehydration
* May see hyponatremia because of water shift from hyperglycemia
- K+:
* Moves from intracellular to extracellular (decreased Na+/K+ ATPase activity)
* May see initial hyperkalemia
* Watch closely after insulin treatment


Hyperosmolar Hyperglycemia Non-ketotic syndrome (Hyperosmolar Coma)
(Cause, Presentation)

- State of profound hyperglycemia induced dehydration and increased serum osmolarity. Classically seen in elderly type 2 diabetics with limited ability to drink (can also be seen in type 1)
- Thirst, polyuria, lethargy, focal neurological deficits (e.g. seizures), that can progress to coma and death if left untreated


Hyperosmolar Hyperglycemia Non-ketotic syndrome (Hyperosmolar Coma)

- Fluid shift from hyperglycemia
- Polyuria ---> decreased extracellular volume ---> reflex activation of sympathetics ---> decreased renal flow and GFR ---> decreased glucose clearance. Combined with increase in counterregulatory hormones ---> increase in glucose
- Loss of intracellular fluid from brain ---> possible coma


Hyperosmolar Hyperglycemia Non-ketotic syndrome (Hyperosmolar Coma)

- Hyperglycemia (often > 600 mg/dL)
- Increased serum osmolarity (> 320 mOsm/kg)
- No acidosis (ketone production inhibited by the presence of insulin


Hyperosmolar Hyperglycemia Non-ketotic syndrome (Hyperosmolar Coma)

- Aggressive IV fluids
- Electrolyte replacement
- Insulin therapy
- Treat the initiating event


Diabetic Ketoacidosis

- Insulin non-compliance
- Increased insulin requirements from stress like infection


Diabetic Ketoacidosis

- Excess fat breakdown and increased ketogenesis from increased free fatty acids (due to increased activity of acetyl CoA carboxylase and unopposed effects of glucagon) ----> ketone bodies (beta-hydroxybutyrate > acetoacetate)
- Decreased blood pH and bicarbonates due to metabolic acidosis
- The increased hydrogen ion secretion will diminish K+ secretion, but the higher than normal tubular flow will promote K+ secretion
- Usually occurs in type 1, as endogenous insulin in type 2 usually prevents lipolysis


Diabetic Ketoacidosis

- Delirium/psychosis
- Kussmaul respiration (rapid/deep breathing)
- Abdominal pain/nausea/vomiting
- Dehydration
- Fruity breath odor (exhaled acetone)


Diabetic Ketoacidosis

- Hyperglycemia
- Increased H+ and decreased HCO3- (anion gap metabolic acidosis)
- Increased blood ketone levels
- Leukocytosis
- Hyperkalemia and depleted intracellular K+
- Hyponatremia (for every 100 mg/dL increase in glucose there will be 1.6 meq decrease in Na+)


Diabetic Ketoacidosis

- Life-threatening mucormycosis (usually caused by Rhizopus infection)
- Cerebral edema
- Cardiac arrhythmias
- Heart failure


Diabetic Ketoacidosis

- IV fluids (about 2-3 liters)
- IV insulin and K+ when K+ level reaches normal range (to replete intracellular stores)
- Bicarbonate (if pH is < 7)
- Glucose if necessary to prevent hypoglycemia
- Treat the underlying cause: non-compliance with medications, infection, pregnancy, or any serious illness


(Cause, Presentation)

- Tumor of pancreatic alpha cells with overproduction of glucagon
- Dermatitis (necrolytic migratory erythema), diabetes (hyperglycemia), DVT, declining weight and depression



- Surgery
- Octreotide


(Cause, Presentation)

- Tumor of pancreatic beta cells with overproduction of insulin
- Hypoglycemia (lethargy, syncope, diplopia)


(Association, Diagnosis)

- 10% associated with MEN 1 syndrome
- Dx: decreased blood glucose with increased insulin and C-peptide levels (vs. exogenous insulin use)



Surgical resection


(Cause, Presentation)

- Tumor of pancreatic delta cells with overproduction of somatostatin that leads to decrease secretion of secretin, cholecystokinin, glucagon, insulin and gastrin
- Diabetes/glucose intolerance, steatorrhea, and gallstones



- Surgical resection
- Octreotide


Diabetes Mellitus
(Complications Pathophysiology)

- Non-enzymatic glycation:
* Small vessel disease (diffuse thickening of basement membrane):
+ Retinopathy (hemorrhage, exudates, microaneurysms, vessel proliferation)
+ Glaucoma
+ Neuropathy
+ Nephropathy (nodular glomerulosclerosis [Kimmelstiel-Wilson nodules] which lead to progressive proteinuria, arteriolosclerosis which lead to hypertension) ---> chronic renal failure
* Large vessel atherosclerosis, CAD, peripheral vascular occlusive disease, gangrene ---> limb loss, cerebrovascular disease. MI most common cause of death
- Osmotic damage (sorbitol accumulation in organs with aldose reductase and decreased or absent sorbitol dehydrogenase):
* Neuropathy (motor, sensory [glove and stocking distribution], and autonomic degeneration)
* Cataracts


Diabetes Mellitus

- Vascular:
* Atherosclerosis, MI and CHF
* Stroke (CVA)
* Peripheral vascular disease (lower extremities loss of hair, claudication, non-healing ulcer, and gangrene)
- Diabetic nephropathy (affects both afferent and efferent artrioles):
* Diffuse glomerulosclerosis
* Nodular glomerulosclerosis
* Pyelonephritis
* Necrotizing papillitis
* Renal failure
- Diabetic retinopathy:
* Non-proliferative phase: microaneurysms, retinal hemorrhages, and exudates
* Proliferative phase: neovascularization (via VEGF)
* Fibrosis phase: vitreous humor fibrosis and retinal detachment
* High rates of cataracts and glaucoma
- Diabetic neuropathy:
* Peripheral neuropathy (glove and stocking)
* Autonomic neuropathy like gastroparesis, esophageal dysmotility, orthostatic hypotension, neurogenic bladder and sexual impotence


Diabetes Mellitus
(Treatment Complications)

- Dawn phenomenon: morning hyperglycemia due to the normal nocturnal release of counterregulatory hormones (e.g. glucagon, epinephrine, cortisol), which increase insulin resistance and blood glucose levels. Rx: Increase P.M. NPH insulin
- Somogyi effect: rebound hyperglycemia that results from excess exogenous insulin, which causes hypoglycemia overnight and stimulates the release of counterregulatory hormones that in turn increase blood glucose levels. Rx: decrease P.M. NPH insulin


Diabetic cardiovascular complications

- The goal Bp should be below 130/80 mmHg. ACEIs/ARBs are first line
- Decrease the LDL to < 100 mg/dL and triglycerides to less than 150 mg/dL with statins
- Low dose aspirin
- Annual screening exams


Diabetic Nephropathy

- Annual screening for microalbuminuria (30-300 mg per 24 hours) [dipstick for urine trace positive at 300 mg of protein per 24 hours]
- When microalbuminuria is +ve start ACEIs or ARBs


Diabetic Gastroparesis

Metoclopromide or erythromycin


Diabetic Retinopathy

- Non-proliferative phase is treated with tight control of blood glucose
- Proliferative phase is treated with laser photo-coagulation (which markedly retards the progression to blindness)


Diabetic Neuropathic pain

- Pregabalin
- Gabapentin
- Tricyclic antidepressants


Diabetes Mellitus

- 2 fasting (> 8 hours) blood glucose more than 125 mg/dL
- Single random blood glucose above 200 mg/dL with symptoms
- Post-prandial (2 hours after oral glucose tolerance test [75 g of glucose in water]) more than 200 mg/dL
- HbA1C more than 6.5%


Diabetes Mellitus
(Health Maintenance)

- Pneumococcal vaccine
- Yearly eye exam to check for proliferative retinopathy
- Statin medication if LDL is above 100 mg/dL
- ACEIs or ARBs if blood pressure is greater than 130/80 mmHg
- ACEIs or ARBs if urine tests +ve for microalbuminuria
- Aspirin, used regularly in all diabetic patients above the age of 30
- Foot exam for neuropathy and ulcers


Diabetes Mellitus
(Screening recommendations)

- Patients with no risk factors: test HbA1C at age of 45; retest every 3 years if its < 5.7% and no other risk factors develop
- Patients with impaired fasting glucose (>110 but less than 125 mg/dL) or impaired glucose tolerance: follow up with frequent retesting


Diabetes Mellitus
(Treatment Goals)

- Tight control of blood glucose in the range of 80-120 mg/dL
- HbA1C is less than 8% in children and less than 7% in adults


Metabolic Syndrome

- Also known as insulin resistance syndrome or syndrome X
- Associated with high risk of CAD and mortality from a cardiovascular event


Metabolic Syndrome

3 out of 5:
- Abdominal obesity (increased waist girth): > 40 inches in men and > 35 inches in women
- Triglycerides > 150 mg/dL
- HDL < 40 mg/dL in men and < 50 mg/dL in women
- Bp more than 130/85 mmHg or a requirement for antihypertensive drugs
- Fasting glucose > 100 mg/dL


Metabolic Syndrome

- Intensive weight loss
- Aggressive cholesterol management and Bp control
- Metformin (has shown to slow onset of diabetes in high risk population)


Diabetes Mellitus
(Lifestyle Modifications)

- Diet: low-fat, moderate carbohydrates, low calorie personalized diet
- Weight loss: 5-10% weight loss with a combination of diet and exercise
- Exercise: moderate-intensity exercise for 30 minutes 5 days per week


Diabetes Mellitus
(Treatment Algorithm)

- Type 1 and gestational DM are treated with basal insulin (like Glargine) + mealtime insulin (rapid acting ones)
- Type 2: do liver function tests first then:
* If abnormal then give insulin
* If normal then check renal function
+ if abnormal don't give metformin
+ If normal then give metformin