Endocrine Pancreas Flashcards
endocrine pancreas
islets of Langerhans, which contain four major and two minor cell types.
The four main types are β, α, δ, and PP (pancreatic polypeptide) cells.
The β cells produce
insulin
α cells secrete
glucagon, which stimulates glycogenolysis in the liver and thus increases blood sugar.
δ cells secrete
somatostatin, which suppresses both insulin and glucagon release.
PP cells secrete
pancreatic polypeptide, which exerts several gastrointestinal effects, such as stimulation of secretion of gastric and intestinal enzymes and inhibition of intestinal motility. These cells not only are present in islets but also are scattered in the exocrine pancreas.
The two rare cell types
D1 cells and enterochromaffin cells.
D1 cells elaborate vasoactive intestinal polypeptide (VIP), a hormone that induces glycogenolysis and hyperglycemia; it also stimulates gastrointestinal fluid secretion and causes secretory diarrhea.
Enterochromaffin cells synthesize serotonin and are the source of pancreatic tumors that cause the carcinoid syndrome
Diabetes Mellitus
Diabetes mellitus is a group of metabolic disorders sharing the common feature of hyperglycemia
In the United States, diabetes is the leading cause of end-stage renal disease, adult-onset blindness and non-traumatic lower extremity amputations resulting from atherosclerosis of the arteries
dx of diabetes mellitus
Blood glucose is normally maintained in a very narrow range of 70 to 120 mg/dL
A fasting plasma glucose ≥ 126 mg/dL
A random plasma glucose ≥ 200 mg/dL
2-hour plasma glucose ≥ 200 mg/dL during an oral glucose tolerance test (OGTT) with a loading dose of 75 gm
A glycated hemoglobin (HbA1C) level ≥ 6.5%
Impaired glucose tolerance (prediabetes)
A fasting plasma glucose between 100 and 125 mg/dL (“impaired fasting glucose”)
2-hour plasma glucose between 140 and 199 mg/dL following a 75-gm glucose OGTT
A glycated hemoglobin (HbA1C) level between 5.7% and 6.4%
Type 1 diabetes
an autoimmune disease characterized by pancreatic β cell destruction and an absolute deficiency of insulin. It accounts for approximately 5% to 10% of all cases, and is the most common subtype diagnosed in patients younger than 20 years of age.
Type 2 diabetes
is caused by a combination of peripheral resistance to insulin action and an inadequate secretory response by the pancreatic β cells (“relative insulin deficiency”). Approximately 90% to 95% of diabetic patients have type 2 diabetes, and the vast majority of such individuals are overweight.
nonketotic hyperosmolar coma
amyloid
Pathogenesis of Type 1 Diabetes Mellitus
an autoimmune disease in which islet destruction is caused primarily by immune effector cells reacting against endogenous β-cell antigens
The fundamental immune abnormality in type 1 diabetes is a failure of self-tolerance in T cells specific for islet antigens
honeymoon period
In the initial 1 or 2 years following the onset of overt type 1 diabetes, the exogenous insulin requirements may be minimal because of ongoing endogenous insulin secretion (referred to as the honeymoon period). Thereafter, any residual β-cell reserve is exhausted and insulin requirements increase dramatically.
Clinical Features of Diabetes
Patients with type 2 diabetes are typically older than 40 years and frequently obese.
In some cases, medical attention is sought because of unexplained fatigue, dizziness, or blurred vision.
Most frequently, however, the diagnosis of type 2 diabetes is made after routine blood testing in asymptomatic persons. In fact, in light of the large number of asymptomatic individuals with undiagnosed hyperglycemia in the United States, routine glucose testing is recommended for everyone older than 45 years of age
The Classic Triad of Diabetes
The onset of type 1 diabetes is usually marked by the triad of polyuria, polydipsia, polyphagia, and, when severe, diabetic ketoacidosis, all resulting from metabolic derangements
Chronic Complications of Diabetes
macrovascular and microvascular disease (chronic hyperglycemia)
Macrovascular disease causes accelerated atherosclerosis among diabetics, resulting in increased risk of myocardial infarction, stroke, and lower extremity ischemia
Microvascular disease are most profound in the retina, kidneys, and peripheral nerves, resulting in diabetic retinopathy, nephropathy, and neuropathy
morphology of pancreatic lesions
reduction in number and size of islets
leukocytic infiltrates in the islets (T lymphocytes)
amyloid deposition within islets in type 2 diabetes
increase in the number and size of islets - in nondiabetic newborns of diabetic mothers.
Diabetic Macrovascular Disease
Myocardial infarction, caused by atherosclerosis of the coronary arteries, is the most common cause of death in diabetics
Gangrene of the lower extremities, as a result of advanced vascular disease, is about 100 times more common in diabetics than in the general population
Diabetic Ocular Complications
Diabetes-induced hyperglycemia leads to acquired opacification of the lens, a condition known as cataract. The most profound histopathologic changes of diabetes are seen in the retina.
Clinical Manifestations of Chronic Diabetes
Macrovascular complications such as myocardial infarction, renal vascular insufficiency, and cerebrovascular accidents are the most common causes of mortality in long-standing diabetes.
Diabetic nephropathy
Visual impairment, sometimes even total blindness,
distal symmetric polyneuropathy of the lower extremities that affects both motor and sensory function
by enhanced susceptibility to infections of the skin and to tuberculosis, pneumonia, and pyelonephritis.
Pancreatic Neuroendocrine Tumors
The preferred term for tumors of the pancreatic islet cells (“islet cell tumors”) is pancreatic neuroendocrine tumors or PanNETs.
The three most common and distinctive clinical syndromes associated with functional pancreatic endocrine neoplasms are:
(1) Hyperinsulinism
(2) Hypergastrinemia and the Zollinger-Ellison syndrome
(3) Multiple endocrine neoplasia (MEN)
Unequivocal criteria for malignancy
metastases, vascular invasion, and local infiltration.
functional status of the tumor has some impact on prognosis
approximately 90% of insulin producing tumors are benign, while 60% to 90% of other functioning and nonfunctioning pancreatic endocrine neoplasms are malignant. Fortunately, insulinomas are the most common subtype of pancreatic endocrine neoplasms.
Hyperinsulinism (Insulinoma)
β-cell tumors (insulinomas) are the most common of pancreatic endocrine neoplasms, and may produce sufficient insulin to induce clinically significant hypoglycemia
hypoglycemic episodes, - the blood glucose level falls below 50 mg/dL of serum.
The clinical manifestations: confusion, stupor, and loss of consciousness. These episodes are precipitated by fasting or exercise and are promptly relieved by feeding or parenteral administration of glucose.
insulinoma morphology
pale to red-brown nodules located anywhere in the pancreas
look like giant islets, with preservation of the regular cords of monotonous cells and their orientation to the vasculature
Deposition of amyloid (pink) is characteristic
Insulin to glucose ratio
with insulinomas
While up to 80% of islet cell tumors demonstrate excessive insulin secretion, the hypoglycemia is mild in all but about 20%, and many cases never become clinically symptomatic.
The critical laboratory findings in insulinomas are high circulating levels of insulin and a high insulin-to-glucose ratio. Surgical removal of the tumor is usually followed by prompt reversal of the hypoglycemia.
Zollinger-Ellison Syndrome (Gastrinomas)
hypersecretion of gastrin
are just as likely to arise in the duodenum and peripancreatic soft tissues as in the pancreas (so-called gastrinoma triangle).
Zollinger and Ellison first called attention to the association of pancreatic islet cell lesions, hypersecretion of gastric acid and severe peptic ulceration, which are present in 90% to 95% of patients.
Clinical Features of gastrinomas
More than 50% of the patients have diarrhea; in 30%, it is the presenting symptom.
Treatment of Zollinger-Ellison syndrome involves control of gastric acid secretion by use of H+K+-ATPase inhibitors and excision of the neoplasm.
Total resection of the neoplasm, when possible, eliminates the syndrome. Patients with hepatic metastases have a shortened life expectancy, with progressive tumor growth leading to liver failure usually within 10 years
α-cell tumors
glucagonomas
- -> increased serum levels of glucagon
- syndrome consisting of mild diabetes mellitus,
- skin rash (necrolytic migratory erythema),
- anemia.
most frequently in perimenopausal and postmenopausal women; extremely high plasma glucagon levels.
δ-cell tumors
somatostatinomas) are associated with diabetes mellitus, cholelithiasis, steatorrhea, and hypochlorhydria. They are exceedingly difficult to localize preoperatively. High plasma somatostatin levels are required for diagnosis.
VIPoma
(watery diarrhea, hypokalemia, achlorhydria, or WDHA syndrome) induces a characteristic syndrome that is caused by release of vasoactive intestinal peptide (VIP) from the tumor. Some of these tumors are locally invasive and metastatic. A VIP assay should be performed on all patients with severe secretory diarrhea.
Pancreatic carcinoid tumors producing serotonin
and an atypical carcinoid syndrome are exceedingly rare. Pancreatic polypeptide-secreting endocrine tumors present as mass lesions as even high plasma levels of this hormone fail to cause symptoms.
