Pancreas Flashcards
(60 cards)
1
Q
Pancreas
Islets of Langerhans cell types
A
All derived from pancreatic buds (embryologically)
- Alpha cells
- Beta cells
- Delta cells
2
Q
Pancreatic Alpha cells
Factoids
A
- 20% of the islet cells
- Secret glucagon
- Located at the periphery
3
Q
Pancreatic Beta cells
Factoids
A
- Major cell type
- Secret insulin (along with C peptide [long term marker])
- Located in the center
- Receive blood first
4
Q
Pancreatic Delta cells
Factoids
A
- 5% of islet cells
- Secrete somatostatin
- Interspersed throughout the pancreas
5
Q
Insulin
Factoids
A
- It is a peptide hormone
- Works through tyrosine kinase
- Anabolic
- Released along with C peptide (its long term marker)
6
Q
Insulin
Effects on Glucose metabolism
A
- 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
7
Q
Insulin
Effects on Protein metabolism
A
- Increases amino acids uptake
- Increases protein synthesis
- Decreases protein degradation
8
Q
Insulin
Effects on Fat metabolism
A
- Decreases hormone sensitive lipase activity
- Increases fatty acids uptake (by stimulating lipoprotein lipase)
- Increases triglycerides synthesis
- Increases acetyl CoA carboxylase enzyme activity
9
Q
Insulin
Glucose storage mechanism
A
Through stimulating the following enzymes (by dephosphorylation):
- Glucokinase
- Glycogen synthase
- PFK-1 (via PFK-2)
- Pyruvate kinase
- Acetyl CoA carboxylase
10
Q
Glucagon
Glucose release mechanism
A
Through stimulating the following enzymes (by phosphorylation):
- Glycogen phosphatase
- Pyruvate carboxylase
- PEPCK
- Fructose 1,6-bisphosphatase
- Glucose-6-phosphatase
11
Q
Insulin
Secretion Stimuli
A
- 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
12
Q
Insulin
Secretion Inhibitors
A
- Somatostatin
- Sympathetic innervation and norepinephrine (alpha-2 receptors)
- Hypokalemia (like in hydrochlorothiazide)
13
Q
Glucagon
Effects
A
- 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)
14
Q
Insulin
Other Effects
A
- Moves K+ into cells by stimulating Na+/K+ ATPase
- Increases Na+ retention (kidneys)
- Decreases glucagon release
15
Q
Glucagon
Secretion Stimuli
A
- Hypoglycemia
- Amino acids like arginine
16
Q
Glucagon
Secretion Inhibitors
A
- Hyperglycemia
- Insulin
- Somatostatin
17
Q
Insulin
Synthesis
A
- Preproinsulin synthesized in RER
- Then cleavage of presignal will produce proinsulin (insulin and C peptide) that is stored in secretory granules
18
Q
Insulin
Secretion
A
- 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
19
Q
Insulin-dependent glucose transports
Names and Locations
A
GLUT-4: in adipose tissue and striated muscles (exercise also increases their expression)
20
Q
Insulin-independent glucose transports
Names and Locations
A
- 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
21
Q
Glucose
Hormonal Control
A
- 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
22
Q
Diabetes Mellitus Type 1 vs. Type 2
Primary Cause, Insulin necessary for Rx, Age, Association with obesity
A
- 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
23
Q
Diabetes Mellitus Type 1 vs. Type 2
Genetic predisposition, HLA system association, Glucose intolerance, Insulin sensitivity
A
- 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
24
Q
Diabetes Mellitus Type 1 vs. Type 2
Ketoacidosis, Beta-cell numbers, Serum insulin level, Classic symptoms [Presentation]
A
- 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
25
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)
Notes:
* 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
26
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
27
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
28
Hyperosmolar Hyperglycemia Non-ketotic syndrome (Hyperosmolar Coma)
(Pathophysiology)
- 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
29
Hyperosmolar Hyperglycemia Non-ketotic syndrome (Hyperosmolar Coma)
(Labs)
- Hyperglycemia (often > 600 mg/dL)
- Increased serum osmolarity (> 320 mOsm/kg)
- No acidosis (ketone production inhibited by the presence of insulin
30
Hyperosmolar Hyperglycemia Non-ketotic syndrome (Hyperosmolar Coma)
(Treatment)
- Aggressive IV fluids
- Electrolyte replacement
- Insulin therapy
- Treat the initiating event
31
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Diabetic Ketoacidosis
(Causes)
```
- Insulin non-compliance
| - Increased insulin requirements from stress like infection
32
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Diabetic Ketoacidosis
(Pathophysiology)
```
- 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
33
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Diabetic Ketoacidosis
(Presentation)
```
- Delirium/psychosis
- Kussmaul respiration (rapid/deep breathing)
- Abdominal pain/nausea/vomiting
- Dehydration
- Fruity breath odor (exhaled acetone)
34
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Diabetic Ketoacidosis
(Labs)
```
- 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+)
35
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Diabetic Ketoacidosis
(Complications)
```
- Life-threatening mucormycosis (usually caused by Rhizopus infection)
- Cerebral edema
- Cardiac arrhythmias
- Heart failure
36
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Diabetic Ketoacidosis
(Treatment)
```
- 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
37
Glucagonoma
| Cause, Presentation
- Tumor of pancreatic alpha cells with overproduction of glucagon
- Dermatitis (necrolytic migratory erythema), diabetes (hyperglycemia), DVT, declining weight and depression
38
Glucagonoma
| Treatment
- Surgery
| - Octreotide
39
Insulinoma
| Cause, Presentation
- Tumor of pancreatic beta cells with overproduction of insulin
- Hypoglycemia (lethargy, syncope, diplopia)
40
Insulinoma
| Association, Diagnosis
- 10% associated with MEN 1 syndrome
| - Dx: decreased blood glucose with increased insulin and C-peptide levels (vs. exogenous insulin use)
41
Insulinoma
| Treatment
Surgical resection
42
Somatostatinoma
| 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
43
Somatostatinoma
| Treatment
- Surgical resection
| - Octreotide
44
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
45
Diabetes Mellitus
| Complications
- 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
46
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
47
Diabetic cardiovascular complications
| Management
- 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
48
Diabetic Nephropathy
| Management
- 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
49
Diabetic Gastroparesis
| Treatment
Metoclopromide or erythromycin
50
Diabetic Retinopathy
| Treatment
- 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)
51
Diabetic Neuropathic pain
| Treatment
- Pregabalin
- Gabapentin
- Tricyclic antidepressants
52
Diabetes Mellitus
| Diagnosis
- 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%
53
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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
54
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
55
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
56
Metabolic Syndrome
| Factoids
- Also known as insulin resistance syndrome or syndrome X
| - Associated with high risk of CAD and mortality from a cardiovascular event
57
Metabolic Syndrome
| Diagnosis
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
58
Metabolic Syndrome
| Treatment
- Intensive weight loss
- Aggressive cholesterol management and Bp control
- Metformin (has shown to slow onset of diabetes in high risk population)
59
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
60
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
