Fa: Endocrine - Pathology - 5

Front 1

What are the acute manifestations of diabetes mellitus?

Back 1

- Polydipsia
- Polyuria
- Polyphagia
- Weight loss
- DKA (diabetic ketoacidosis) (type 1)
- Hyperosmolar coma (type 2)

Front 2

What can, although rarely, cause Diabetes Mellitus?

Back 2

Unopposed secretion of GH and Epinephrine

Front 3

What are the immediate consequences of an insulin deficiency (and glucagon excess)?

Back 3

- Decreased glucose uptake
- Increased protein catabolism
- Increased lipolysis

Front 4

What is the effect of decreased glucose uptake (due to insulin deficiency / glucagon excess)?

Back 4

- Hyperglycemia
- Glycosuria (excess of sugar in the urine)
- Osmotic diuresis
- Electrolyte depletion

Front 5

What is the effect of increased protein catabolism (due to insulin deficiency / glucagon excess)?

Back 5

- Increased plasma amino acids
- Nitrogen loss in urine

Front 6

What is the effect of increased lipolysis (due to insulin deficiency / glucagon excess)?

Back 6

- Increased plasma FFAs
- Ketogenesis
- Ketonuria
- Ketonemia

Front 7

What is the combined effect of decreased glucose uptake, increased protein catabolism, and increased lipolysis (due to insulin deficiency / glucagon excess)?

Back 7

Dehydration and acidosis, which can cause coma or death

Front 8

What are the types of damage due to chronic diabetes?

Back 8

- Non-enzymatic glycosylation: small vessel and large vessel disease
- Osmotic damage: neuropathy, cataracts

Front 9

What are the manifestations of non-enzymatic glycosylation on small vessels in patients with chronic diabetes?

Back 9

Diffuse thickening of basement membrane of small vessels leads to:
- Retinopathy
- Glaucoma
- Nephropathy

Front 10

How are the eyes of patients with chronic diabetes affected?

Back 10

Small vessel disease due to diffuse thickening of basement membrane via non-enzymatic glycosylation:
- Retinopathy (picture): hemorrhage, exudates, microaneurysms, vessel proliferation
- Glaucoma

Front 11

How are the kidneys of patients with chronic diabetes affected?

Back 11

Small vessel disease (diffuse thickening of basement membrane) via non-enzymatic glycosylation:
- Nephropathy: nodular sclerosis, progressive proteinuria, chronic renal failure, arteriolosclerosis leading to HTN, Kimmelstiel-Wilson nodules)

Front 12

What are the manifestations of retinopathy in chronic diabetes mellitus?

Back 12

- Hemorrhage
- Exudates
- Microaneurysms
- Vessel proliferation

Front 13

What are the manifestations of nephropathy in chronic diabetes mellitus?

Back 13

- Nodular sclerosis
- Progressive proteinuria
- Chronic renal failure
- Arteriolosclerosis leading to HTN
- Kimmelstiel-Wilson nodules

Front 14

What are the manifestations of non-enzymatic glycosylation on large vessels in patients with chronic diabetes?

Back 14

- Large vessel atherosclerosis → cerebrovascular disease
- CAD → MI (most common cause of death)
- Peripheral vascular occlusive disease
- Gangrene → limb loss

Front 15

What is the most common cause of death in patients with Diabetes Mellitus?

Back 15

Myocardial Infarction

Front 16

What causes osmotic damage in patients with chronic diabetes?

Back 16

Sorbitol accumulates in organs with aldose reductase and ↓ or absent sorbitol dehydrogenase

Front 17

What are the manifestations of osmotic damage in patients with chronic diabetes?

Back 17

- Neuropathy: motor, sensory, and autonomic degeneration
- Cataracts

Front 18

What tests can be used to assess a patient's diabetes mellitus?

Back 18

- Fasting serum glucose
- Oral glucose tolerance test
- HbA1c (reflects average blood glucose over prior 3 months)

Front 19

What is the primary defect in T1DM vs T2DM?

Back 19

- T1DM: auto-immune destruction of β cells
- T2DM: ↑ resistance to insulin, progressive pancreatic β-cell failure

Front 20

Is insulin necessary in treatment of T1DM and T2DM?

Back 20

- T1DM: always
- T2DM: sometimes

Front 21

What is the typical age of onset for patients with T1DM vs T2DM?

Back 21

- T1DM: <30 years
- T2DM: >40 years

*Exceptions commonly occur

Front 22

What is the association with obesity for T1DM vs T2DM?

Back 22

- T1DM: none
- T2DM: associated

Front 23

Is there a genetic predisposition for T1DM vs T2DM?

Back 23

- T1DM: relatively weak (50% concordance in identical twins), polygenic
- T2DM: relatively strong (90% concordance in identical twins), polygenic

Front 24

What is the association with HLA system for T1DM vs T2DM?

Back 24

- T1DM: associated with HLA-DR3 and -DR4
- T2DM: no association

Front 25

What is the relative glucose intolerance in T1DM vs T2DM?

Back 25

- T1DM: severe
- T2DM: mild to moderate

Front 26

What is the relative insulin sensitivity in T1DM vs T2DM?

Back 26

- T1DM: high
- T2DM: low

Front 27

How common is ketoacidosis in T1DM vs T2DM?

Back 27

- T1DM: common
- T2DM: rare

Front 28

How many β-cells are there in the islets relatively in T1DM vs T2DM?

Back 28

- T1DM: ↓ β-cell numbers
- T2DM: variable (with amyloid deposits)

Front 29

What is the relative serum insulin level in T1DM vs T2DM?

Back 29

- T1DM: ↓
- T2DM: Variable

Front 30

Are the classic symptoms of polyuria, polydipsia, polyphagia, and weight loss seen in T1DM vs T2DM?

Back 30

- T1DM: common
- T2DM: sometimes

Front 31

What is the histologic appearance of the Islets of Langerhans in T1DM vs T2DM?

Back 31

- T1DM: islet leukocytic infiltrate (auto-immune process)
- T2DM: islet amyloid polypeptide (IAPP) deposits

Front 32

What is one of the most important complications of diabetes (usually type 1)?

Back 32

Diabetic Ketoacidosis

Front 33

What causes diabetic ketoacidosis?

Back 33

- Complication of diabetes (usually type 1)
- Usually due to ↑ insulin requirements from ↑ stress (eg, infection)
- Excess fat breakdown and ↑ ketogenesis from ↑ FFAs, when are converted into ketone bodies

Front 34

What are the types of ketone bodies? Which is more common in diabetic ketoacidosis?

Back 34

β-Hydroxybutyrate > Acetoacetate

Front 35

What are the signs / symptoms of diabetic ketoacidosis?

Back 35

- Kussmaul respirations (rapid / deep breathing)
- Nausea / vomiting
- Abdominal pain
- Psychosis / delirium
- Dehydration
- Fruity breath odor (due to exhaled acetone)

Front 36

What are Kussmaul respirations? Sign of?

Back 36

- Rapid / deep breathing
- Sign of diabetic ketoacidosis

Front 37

What causes the fruity breath odor in diabetics?

Back 37

Diabetic ketoacidosis → exhaled acetone

Front 38

What are the lab findings associated with diabetic ketoacidosis?

Back 38

- Hyperglycemia
- ↑ H+ and ↓ HCO3- (anion gap metabolic acidosis)
- ↑ Blood ketone levels
- Leukocytosis
- Hyperkalemia, but depleted intracellular K+ d/t transcellular shift from ↓ insulin

Front 39

What kind of acid/base disturbance occurs with diabetic ketoacidosis?

Back 39

Anion gap metabolic acidosis
- ↑ H+
- ↓ HCO3-

Front 40

How are WBCs affected in diabetic ketoacidosis?

Back 40

Leukocytosis

Front 41

How is K+ balance affected in diabetic ketoacidosis?

Back 41

- Hyperkalemia
- Depleted intracellular K+ because of transcellular shift from ↓ insulin

Front 42

What are the potenial complications of diabetic ketoacidosis?

Back 42

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

Front 43

How do you treat diabetic ketoacidosis?

Back 43

- IV fluids
- IV insulin
- K+ (to replete intracellular stores)
- Glucose if necessary to prevent hypoglycemia

Front 44

What is the source of an insulinoma? What is its effect?

Back 44

- Tumor of β cells of pancreas
- Over-produces insulin → hypoglycemia

Front 45

What are the common symptoms with an insulinoma?

Back 45

Whipple triad of episodic CNS symptoms:
- Lethargy
- Syncope
- Diplopia

Front 46

What lab values are associated with insulinoma?

Back 46

- ↓ Blood glucose
- ↑ C-peptide (vs exogenenous insulin use which would cause similar findings but have low/normal C-peptide)

Front 47

How do you treat an insulinoma?

Back 47

Surgical resection of tumor in pancreas

Front 48

What is the most common malignancy in the small intestine?

Back 48

Carcinoid Syndrome

Front 49

What causes Carcinoid Syndrome?

Back 49

Rare syndrome caused by carcinoid tumors (neuroendocrine cells), especially metastatic small bowel tumors, which secrete high levels of serotonin (5-HT)

Front 50

What is necessary for a carcinoid tumor of the small intestine to cause Carcinoid Syndrome?

Back 50

- Tumor secretes high levels of serotonin (5-HT)
- Tumor must not be restricted to the GI tract because 5-HT undergoes first pass metabolism in the liver

Front 51

What are the symptoms of Carcinoid Syndrome?

Back 51

- Recurrent diarrhea
- Cutaneous flushing
- Asthmatic wheezing
- Right sided valvular disease

Front 52

What are the lab changes associated with Carcinoid Syndrome?

Back 52

- ↑ 5-hydroxyindoleacetic acid (5-HIAA) in urine
- Niacin deficiency (pellagra - diarrhea, dementia, dermatitis)

Front 53

How do you treat Carcinoid Syndrome?

Back 53

- Resection of carcinoid tumor
- Somatostatin analog (eg, octreotide)

Front 54

What is the rule of 1/3 for Carcinoid Syndrome?

Back 54

- 1/3 metastasize
- 1/3 present with 2nd malignancy
- 1/3 are multiple

Front 55

What causes Zollinger-Ellison Syndrome?

Back 55

- Gastrin-secreting tumor of pancreas or duodenum
- Leads to acid hyper-secretion → recurrent ulcers in distal duodenum and jejunum

Front 56

Zollinger-Ellison Syndrome leads to ulcers where?

Back 56

Distal duodenum and jejunum

Front 57

What symptoms does a patient with Zollinger-Ellison Syndrome typically present with?

Back 57

- Abdominal pain (peptic ulcer disease, distal ulcers)
- Diarrhea (malabsorption)

Front 58

What may Zollinger-Ellison Syndrome be associated with?

Back 58

MEN 1

Front 59

What are the types of Multiple Endocrine Neoplasias?

Back 59

- MEN 1 (Wermer syndrome)
- MEN 2A (Sipple syndrome)
- MEN 2B

Front 60

What kind of tumors are associated with MEN 1?

Back 60

MEN 1 = 3 P's (diamond):
- Pituitary tumors (prolactin or GH)
- Parathyroid tumors
- Pancreatic endocrine tumors (Zollinger Ellison syndrome, insulinomas, VIPomas, glucagonomas-rare)

Front 61

Besides pituitary tumors, parathyroid tumors, and pancreatic endocrine tumors, what else is associated with MEN 1?

Back 61

- Kidney stones
- Stomach ulcers

Front 62

What kind of tumors are associated with MEN 2A?

Back 62

MEN 2A: 2 P's (square):
- Parathyroid (hyperplasia)
- Pheochromocytoma (adrenals)

- Medullary Thyroid Carcinoma (secretes calcitonin)

Front 63

Besides medullary thyroid carcinoma, pheochromocytoma, and parathyroid hyperplasia, what else is associated with MEN 2A?

Back 63

Associated with RET gene mutations

Front 64

What kind of tumors are associated with MEN 2B?

Back 64

MEN 2B: 1 P (triangle):
- Pheochromocytoma (adrenals)

- Oral / intestinal ganglioneuromatosis (mucosal neuromas)
- Medullary Thyroid Carcinoma (secretes calcitonin)

Front 65

Besides medullary thyroid carcinoma, pheochromocytoma, and oral/intestinal ganglioneuromatosis (mucosal neuromas), what else is associated with MEN 2B?

Back 65

Marfanoid habitus
- Resembling symptoms of Marfan Syndrome
- Long limbs, arachnodactyly, and hyperlaxity
- Arm span is greater than the height of the individual

Associated with RET gene mutation

Front 66

How are MEN syndromes inherited? Other associated genetic changes?

Back 66

- All are autosomal dominant (think "MEN are dominant" - or so they think)
- Associated with RET gene mutation in MEN 2A and 2B