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Flashcards in Pancreas Deck (60)
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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
Q

Insulin Deficiency

Metabolic Effects

A
  • 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
Q

Insulin Deficiency

Effects on Na+ and K+

A
  • 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
Q

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

A
  • 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
Q

Hyperosmolar Hyperglycemia Non-ketotic syndrome (Hyperosmolar Coma)
(Pathophysiology)

A
  • 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
Q

Hyperosmolar Hyperglycemia Non-ketotic syndrome (Hyperosmolar Coma)
(Labs)

A
  • Hyperglycemia (often > 600 mg/dL)
  • Increased serum osmolarity (> 320 mOsm/kg)
  • No acidosis (ketone production inhibited by the presence of insulin
30
Q

Hyperosmolar Hyperglycemia Non-ketotic syndrome (Hyperosmolar Coma)
(Treatment)

A
  • Aggressive IV fluids
  • Electrolyte replacement
  • Insulin therapy
  • Treat the initiating event
31
Q
Diabetic Ketoacidosis
(Causes)
A
  • Insulin non-compliance

- Increased insulin requirements from stress like infection

32
Q
Diabetic Ketoacidosis
(Pathophysiology)
A
  • 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
Q
Diabetic Ketoacidosis
(Presentation)
A
  • Delirium/psychosis
  • Kussmaul respiration (rapid/deep breathing)
  • Abdominal pain/nausea/vomiting
  • Dehydration
  • Fruity breath odor (exhaled acetone)
34
Q
Diabetic Ketoacidosis
(Labs)
A
  • 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
Q
Diabetic Ketoacidosis
(Complications)
A
  • Life-threatening mucormycosis (usually caused by Rhizopus infection)
  • Cerebral edema
  • Cardiac arrhythmias
  • Heart failure
36
Q
Diabetic Ketoacidosis
(Treatment)
A
  • 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
Q

Glucagonoma

Cause, Presentation

A
  • Tumor of pancreatic alpha cells with overproduction of glucagon
  • Dermatitis (necrolytic migratory erythema), diabetes (hyperglycemia), DVT, declining weight and depression
38
Q

Glucagonoma

Treatment

A
  • Surgery

- Octreotide

39
Q

Insulinoma

Cause, Presentation

A
  • Tumor of pancreatic beta cells with overproduction of insulin
  • Hypoglycemia (lethargy, syncope, diplopia)
40
Q

Insulinoma

Association, Diagnosis

A
  • 10% associated with MEN 1 syndrome

- Dx: decreased blood glucose with increased insulin and C-peptide levels (vs. exogenous insulin use)

41
Q

Insulinoma

Treatment

A

Surgical resection

42
Q

Somatostatinoma

Cause, Presentation

A
  • 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
Q

Somatostatinoma

Treatment

A
  • Surgical resection

- Octreotide

44
Q

Diabetes Mellitus

Complications Pathophysiology

A
  • 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
Q

Diabetes Mellitus

Complications

A
  • 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
Q

Diabetes Mellitus

Treatment Complications

A
  • 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
Q

Diabetic cardiovascular complications

Management

A
  • 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
Q

Diabetic Nephropathy

Management

A
  • 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
Q

Diabetic Gastroparesis

Treatment

A

Metoclopromide or erythromycin

50
Q

Diabetic Retinopathy

Treatment

A
  • 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
Q

Diabetic Neuropathic pain

Treatment

A
  • Pregabalin
  • Gabapentin
  • Tricyclic antidepressants
52
Q

Diabetes Mellitus

Diagnosis

A
  • 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
Q
Diabetes Mellitus
(Health Maintenance)
A
  • 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
Q

Diabetes Mellitus

Screening recommendations

A
  • 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
Q

Diabetes Mellitus

Treatment Goals

A
  • 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
Q

Metabolic Syndrome

Factoids

A
  • Also known as insulin resistance syndrome or syndrome X

- Associated with high risk of CAD and mortality from a cardiovascular event

57
Q

Metabolic Syndrome

Diagnosis

A

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
Q

Metabolic Syndrome

Treatment

A
  • Intensive weight loss
  • Aggressive cholesterol management and Bp control
  • Metformin (has shown to slow onset of diabetes in high risk population)
59
Q

Diabetes Mellitus

Lifestyle Modifications

A
  • 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
Q

Diabetes Mellitus

Treatment Algorithm

A
  • 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