Endocrine Pancreas Pathology

Question 1

Which ethnicities are more likely to develop DM?

Answer 1

Native Americans
African Americans
Hispanics

Question 2

What are the criteria for Dx of DM?

Answer 2

Fasting glucose ≥ 126
Random glucose ≥ 200
2-hour glucose ≥ 200 during OGTT
HbA1C ≥ 6.5%

Question 3

What is the pathogenesis of DM1?

Answer 3

Islet cell destruction caused by immune effector cells reacting against endogenous ß-cell Ags

Question 4

What are the potential autoAg targets in DM1?

Answer 4

Insulin
ß-cell enzyme Glutamic Acid decarboxylase (GAD)
Islet cell autoAg 512 (ICA512)

Question 5

What HLA’s are associated with DM1?

Answer 5

HLA-DR3, HLA-DR4

Question 6

Which other HLA mutation gives the highest risk for DM1?

Answer 6

HLA-DR8

Question 7

Which chromosome are the HLA’s on for DM1?

Answer 7

Chrom 6p21

Question 8

Which polymorphisms are seen in DM1?

Answer 8

CTLA4
PTPN22
AIRE
Wasinsulin

Question 9

What is the classic Sx triad for DM1?

Answer 9

Polyuria
Polydipsia
Polyphagia

Question 10

What is the “honeymoon” period?

Answer 10

Endogenous insulin secretion is enough to need little exogenous insulin

Question 11

Is DKA more likely in DM1 or DM2?

Answer 11

DM1

Question 12

When does DM1 typically present?

Answer 12

< 18 yo

Question 13

What is the biggest risk factor for DM2?

Answer 13

Central/Visceral obesity

Question 14

What is the pathogenesis of DM2?

Answer 14

Insulin resistance –> decreased response of peripheral tissues to insulin

Question 15

How does insulin resistance affect the liver?

Answer 15

Failure to inhibit gluconeogenesis –> high fasting blood glucose

Question 16

How does insulin resistance affect the SkM?

Answer 16

Failure of glucose uptake and glycogen synthesis after a meal –> high post-prandial blood glucose

Question 17

How does insulin resistance affect adipose tissue?

Answer 17

Failure to inhibit activation of lipase –> excess TG breakdown and high circulating FFA’s

Question 18

When does DM2 typically present?

Answer 18

> 40 yo

Question 19

What are the main Sx’s of DM2 at presentation?

Answer 19

Fatigue
Dizziness
Blurred vision

Question 20

What is Hyperosmolar Hyperosmotic Syndrome (HHS)?

Answer 20

Severe dehydration from sustained osmotic diuresis

Question 21

What type of pts typically get Hyperosmolar Hyperosmotic Syndrome?

Answer 21

Older pts disabled by stroke or infection

Question 22

What is the blood glucose range for pts with Hyperosmolar Hyperosmotic Syndrome?

Answer 22

600-1200 mg/dL

Question 23

What is Lipoatrophic diabetes?

Answer 23

Hyperglycemia along with loss of adipose tissue in subQ fat

Question 24

Pregnant women with pregestational DM that isn’t controlled put their fetuses at increased risk for?

Answer 24

Stillbirth

Congenital malformations

Question 25

Why do pregnant women develop gestational DM?

Answer 25

Pregnancy is a diabetogenic state where the hormones favor a state of insulin resistance

Question 26

Do pregnant women who get gestational DM have a increased risk of developing overt DM?

Answer 26

Yes, 10-20 years later

Question 27

What factors can trigger DKA?

Answer 27

Failure to take insulin* Infection, Illness Trauma Drugs

Question 28

What is the typically serum glucose level in DKA?

Answer 28

250-600 mg/dL

Question 29

What are the major Sx's of DKA?

Answer 29

Fatigue, N/V, ab pain, fruity breath, labored breathing (Kussmaul), CNS depression

Question 30

What is the MOA of DKA?

Answer 30

Insulin deficiency --> stimulation of lipases --> increased FFA's in serum --> increased fatty acyl-CoA production in liver --> oxidation of fatty acyl-CoA into ketone bodies

Question 31

What are the two ketone bodies of concern in DKA?

Answer 31

Acetoacetic acid | ß-hydroxybutyric acid

Question 32

How does metabolic ketoacidosis occur?

Answer 32

Dehydration --> decreased urinary excretion of ketone bodies

Question 33

What is the Tx for DKA?

Answer 33

Insulin administration Correct metabolic acidosis Tx precipitating factor

Question 34

What is the most common acute metabolic complication in either type of DM?

Answer 34

Hypoglycemia

Question 35

What are the Sx's of hypoglycemia?

Answer 35

Dizziness, confusion, sweating, palpitations, tachycardia

Question 36

What is used to assess glycemic control?

Answer 36

HbA1C

Question 37

Why does HbA1C help assess glycemic control?

Answer 37

The more glucose that has been around an RBC, the more HbA1C will be present

Question 38

What is the most common cause of death in DM pts?

Answer 38

MI

Question 39

Pts with DM have increased PAI-1 enzyme, meaning...

Answer 39

Increased inhibition of fibrinolysis = acts as procoagulatin

Question 40

Morphology = diffuse thickening of basement membranes of vessels with paradoxical increased leakiness of vessels

Answer 40

Diabetic microvascular disease

Question 41

What is the first sign of diabetic nephropathy?

Answer 41

Microalbuminuria

Question 42

What is a urinary marker for increased CV risk?

Answer 42

Albumin

Question 43

Which ethnicities (with DM2) are at greater risk for developing diabetic nephropathy?

Answer 43

Native Americans African Americans Hispanics

Question 44

What are the 3 major lesions seen in the kidney in diabetic nephropathy?

Answer 44

Glomerular lesions Nodular Glomerulosclerosis Pyelonephritis (necrotizing papillitis)

Question 45

What glomerular lesion is seen in diabetic nephropathy?

Answer 45

Thickening of the basement membrane

Question 46

What is seen in Diffuse Mesangial Sclerosis?

Answer 46

Increase mesangium with thickend GBM

Question 47

In Diffuse Meesangial Sclerosis, the matrix will stain + for?

Answer 47

PAS

Question 48

What is the name for nodules that enlarge and eventually obliterate the glomerular tuft in the kidney?

Answer 48

Nodular Glomerulosclerosis (Kimmelstiel-Wilson) disease

Question 49

What can happen to the afferent and efferent hilar arterioles in diabetic nephropathy?

Answer 49

Hyalinosis due to ischemia

Question 50

Which type of pyelonephritis is more common in pts with diabetic nephropathy?

Answer 50

Necrotizing papillitis

Question 51

Sx's = motor and sensory dysfunction of the distal LE's and UE's

Answer 51

Diabetic neuropathy

Question 52

What are the Sx's of autonomic neuropathy?

Answer 52

Bowel, bladder, and ED

Question 53

What are the Sx's of mononeuropathy?

Answer 53

Sudden foot drop, wrist drop, or isolated CN palsies

Question 54

What is the pathogenesis of diabetic ocular complications?

Answer 54

Neovascularization from hypoxia-induced overexpression of VEGF in the retina

Question 55

What type of cells are involved in pancreatic neuroendocrine tumors?

Answer 55

Islet cells

Question 56

Islet cell tumors secreting insulin are mostly _____ while islet cell tumors secreting other hormones are mostly _____

Answer 56

Benign | Malignant

Question 57

What mutations are commonly seen in Pancreatic Neuroendocrine tumors?

Answer 57

MEN1, PTEN, TSC2 A-Thalaseemia/Mental retardation syndrome, X-linked (ATRX) Death-domain Associated protein (DAXX)

Question 58

What is the most common pancreatic endocrine neoplasm?

Answer 58

Insulinoma

Question 59

What are the Sx's of an Insulinoma?

Answer 59

Hypoglycemia with confusion, stupor, and LOC

Question 60

Morphology = small cells that look like giant cells with amyloid deposition

Answer 60

Insulinoma

Question 61

What lab value would indicate and Insulinoma?

Answer 61

High circulating insulin | High insulin:glucose ratio

Question 62

What is the Tx for an Insulinoma?

Answer 62

Surgical removal

Question 63

Sx's = peptic ulcers, diarrhea, possible MEN1 syndrome

Answer 63

Gastrinoma (ZE)

Question 64

Sx's = mild DM with skin rash and anemia in perimenopausal and postmenopausal women

Answer 64

a-cell tumors (Glucagonomas)

Question 65

Sx's = DM, cholelithiasis, steatorrhea, and hypochlorhydria

Answer 65

d-cell tumors (Somatostatinomas)

Question 66

Sx's = watery diarrhea, hypokalemia, achlorhydria (WDHA syndrome)

Answer 66

VIPoma