Pancreas

Dr. Mohannad Abulihya

The Pancreas

1.Exocrine gland: ~ 90%

– Secretes enzymes for food digestion
– The most significant disorders:
• Acute and chronic pancreatitis
• Pancreatic carcinoma
2. Endocrine gland: ~ 10%
– Consisting of the islets of Langerhans
• – Secretes insulin and glucagon
• – The most common disorder is diabetes mellitus (DM)
Acute pancreatitis

• Characterized by:
• Enzymatic necrosis and inflammation
• Autodigestion of the pancreas by
inappropriately activated pancreatic
enzymes

• Elevation of pancreatic enzymes in

blood and urine
-Amylase
-Lipases (cause fat necrosis)

• Acute hemorrhagic pancreatitis

• Common complication is pseudocysts

• Several conditions can lead to acute pancreatitis, including:
1. Blockage in the bile duct caused by gallstones.
2. Heavy alcohol use.
3. Certain medicines.
4. High triglyceride levels in the blood.
5. High calcium levels in the blood.
6. Pancreas cancer.
7. Injuries from trauma or surgery.
Acute pancreatitis.
The pancreas has been sectioned across to reveal dark areas of hemorrhage
in the pancreatic substance and a focal area of pale fat necrosis in the
peripancreatic fat (upper left)
Acute pancreatitis: Clinical features
• Epigastric abdominal pain with radiation to the back
• Shock
• Jaundice, hyperglycemia, and glycosuria
• Hypocalcemia
• Diagnosis:
–Elevated serum amylase
–Rises within the first 12 hrs
–Return to normal within 48 to 72 hrs
–Elevated serum lipase
–CT
• The mortality rate with severe acute pancreatitis is ~20-40%
 Chronic pancreatitis
• Characterized by:
• Repeated bouts of mild to moderate pancreatic
inflammation
• Loss of pancreatic parenchyma and fibrosis
• Most frequently affects middle-aged men

• Causes:
–Alcohol: the most common
–Biliary tract disease
–Hypercalcemia
–Hyperlipoproteinemia

• – Idiopathic pancreatitis in ~50%

Chronic pancreatitis: Clinical features
• Asymptomatic
• Repeated attacks of abdominal pain and back pain
• Recurrent attacks of jaundice
• Diabetes mellitus
• Chronic malabsorption
• Diagnosis:
–Mild elevations of serum amylase and lipase levels
–X-rays, CT, US:
•Visualization of calcifications
•Identification of pseudocyst
 Pancreatic cancer
• Carcinoma of the pancreas
• Arising mainly in the exocrine portion of
the gland
• The fourth most frequent cause of death
from CA
• Peak incidence between 60-80 yrs

• All are adenocarcinomas:

1. Carcinoma of the head of the pancreas ~
70%
– Obstructing the outflow of bile
2. Carcinomas of the body and tail: ~30%
– No obstruction to bile duct, no jaundice
– Usually remain silent
Carcinoma of the pancreas, clinical features
• Asymptomatic
• Abdominal pain with radiation to the back
• Obstructive jaundice:
–Occurs mainly with CA of pancreatic head
• Migratory thrombophlebitis:
–Called Trousseau’s sign.
–Occurs mainly with CA of the body and tail (not well understood)
• Diagnosis:
–Ultra Sound, CT scan and biopsy
Endocrine pancreas
Endocrine pancreas
• Diabetes Mellitus:
–Chronic disorder of carbohydrate, fat, and protein metabolism

–Deficiency in insulin

–Impaired glucose use, resulting in hyperglycemia

Metabolic actions of insulin in striated muscle,
adipose tissue, and liver
Diabetes
Starvation in the midst of plenty.
Swimming in a sea of sugar that cannot be utilized.
I. Type 1 diabetes: ~ 10%
A. Immune mediated (type 1A)
B. Idiopathic (type 1B)

II. Type 2 diabetes: ~ 80%

III. Other specific types of diabetes:

A. Genetic defects of beta-cell function characterized by mutations in
1. Hepatocyte nuclear transcription factor (HNF) 4α
2. Glucokinase
3. Hepatocyte nuclear transcription factor 1α
4. Insulin promoter factor
B. Genetic defects in insulin action (e.g., type A insulin resistance)
C. Diseases of exocrine pancreas: pancreatitis, pancreatectomy, neoplasia, cystic fibrosis, hemochromatosis
D. Endocrinopathies: Cushing syndrome, acromegaly, pheochromocytoma, hyperthyroidism, glucagonoma
E. Drugs or chemicals: glucocorticoids, thiazides
F. Infections: congenital rubella, cytomegalovirus, coxsackievirus, others
G. Uncommon forms of immune-mediated diabetes: "Stiff man" syndrome, anti-insulin receptor antibodies
H. Genetic syndromes: Down syndrome, Klinefelter syndrome

IV. Gestational diabetes mellitus

Diabetes Mellitus (DM)
• Type 1 diabetes: 10%
• Called insulin-dependent DM
• Juvenile-onset diabetes
• Two subgroups:

Type 1A:
– The most common form
– Caused by autoimmune destruction of beta cells
Type 1B:
– Associated with severe insulin deficiency
– No evidence of autoimmunity
Type 1 DM : Clinical features
• Polyuria

• Polydipsia

• Polyphagia

• Weight loss

• Hyperglycemia, hyperlipidemia

• Ketoacidosis
Sequence of metabolic events leading to
diabetic coma in type 1 DM:
• Insulin deficiency leads to a catabolic state, ketoacidosis
and severe volume depletion. These cause CNS
compromise, can lead to coma and eventual death if left
untreated.
Diabetes Mellitus Type 2
• Type 2 diabetes: 80%
• Called non-insulin-dependent DM
• Adult-onset diabetes
• Life style clearly plays a role

• Multifactorial disorder involving:

1.Impaired insulin release
2.End organ insensitivity
Type 2 DM : Clinical Features
• Patients are >40 years
• Often asymptomatic
• Polyuria
• Polydipsia
• Weight loss
• Hyperosmolar nonketotic coma:
–Severe dehydration
–The patient is elderly with limited mobility
–Severe hyperglycemia
• 28
Morphology of Pancreas in DM
• Reduction in the number and size of islets
–Mainly in type 1 diabetes

• Leukocytic infiltration of the islets (insulitis)

–type 1A diabetes

• Amyloid replacement of islets and fibrosis

–type 2 diabetes
 Type 1 versus Type 2 Diabetes Mellitus
Type 1 Type 2
Clinical Children > adults Adults > children
Normal weight Obese
Decreased blood insulin Normal or increased blood insulin

Anti-islet cell antibodies No anti-islet cell antibodies

Ketoacidosis common Ketoacidosis rare
Genetics 40% concordance in twins 60% to 80% concordance in twins

HLA-D linked No HLA association

Pathogenesis Autoimmunity, immunopathologic Insulin resistance
mechanisms
Severe insulin deficiency Relative insulin deficiency
Islet Cells Insulitis early No insulitis
Marked atrophy and fibrosis Focal atrophy and amyloid
deposits
Mild beta-cell depletion
Complications of Diabetes (DM 1 & 2)
• In most patients, they appear after 10 - 15 years
1.Microangiopathy
2.Retinopathy
3.Nephropathy
4.Neuropathy
5.Accelerated atherosclerosis
Complications of DM : vascular system
• Accelerated severe atherosclerosis
• Hyaline arteriolosclerosis associated with HTN
• Myocardial infarction:
– the most common cause of death in DM

• Gangrene of the lower extremities

• Diabetic microangiopathy:
– diffuse thickening of basement membranes
Complications of DM :
diabetic nephropathy (ESRD)
• Three important lesions:

• Glomerular lesions
• Diffuse and nodular glomerulosclerosis
• Capillary basement membrane thickening

• Renal vascular lesions:

• Renal atherosclerosis and arteriolosclerosis

• Pyelonephritis, including necrotizing papillitis

• Nephrosclerosis in a patient with long-standing diabetes. The kidney has
been bisected to demonstrate both diffuse granular transformation of the
surface (left) and marked thinning of the cortical tissue (right)

• 38
 • Diabetic Ocular Complications

• Retinopathy, two forms:

1.nonproliferative (background) retinopathy
2.proliferative retinopathy

• Cataract formation

• Glaucoma
 • Nonproliferative Retinopathy
• Includes:
1. Hemorrhage: intraretinal or preretinal
2. Microaneurysms
3. Venous dilations and edema
4. Retinal exudates:
• Soft (microinfarcts)
• Hard (deposits of plasma proteins and lipids)
5. Microangiopathy: thickening of the retinal capillaries
• 40
 • Proliferative Retinopathy

• Includes:
• Neovascularization
• Fibrosis

• Complications:
–Vitreous hemorrhages
–Retinal detachment
• 41
Non-proliferative (Background) Retinopathy
• Diabetic retinopathy: A view of the fundus shows large areas of preretinal
hemorrhage below the optic disc; pale dots represent exudates in the left side.
Neovascularization is present on the right side of the optic disc
• Glaucoma is caused by high pressure in the eye damaging the optic
nerve, which results in loss of individual nerve cells. This causes a
subsequent increase in the size of the cup, also called cupping.

• Glaucoma with marked cupping of the optic disk is seen on

funduscopic examination.
Normal range of visionVision loss from glaucoma
• Cataracts are morefrequent in personswith DM
Diabetic Neuropathy

• Includes:
• Both motor and sensory function
• Peripheral, symmetric neuropathy of lower extremities
• Autonomic neuropathy: produces disturbances in bowel and bladder
function, and sexual impotence
• Diabetic mononeuropathy: e.g. foot-drop, wrist-drop
• Microangiopathy
• Cerebrovascular infarcts and brain hemorrhages

• 48
Diabetic vasculopathy
• A diabetic foot with a previous healed amputation demonstrates an
ulcer in the region of the ankle

• 49
Laboratory Diagnosis of DM:

1. Fasting venous plasma glucose concentrations of 126 mg/dL or greater on more

than one occasion

2. Random glucose level of 200 mg/dL or greater and clinical symptoms of diabetes

3. Oral glucose tolerance test: after ingestion of 75g of glucose, a 2-hour venous plasma

glucose concentration of 200 mg/dL or greater

• 50
Tests for monitoring diabetes
• Urine glucose and/or ketones:
– Glycosuria and ketonuria

• Protein Glycosylation:
–Measurement of glycosylated hemoglobin (HbA1c)
• Levels in blood (a glucose molecule covalently attached to Hb) It is also a
good way of determining whether the patients are compliant.
• Provides an index of the average blood glucose levels over the 120-day life
span of erythrocytes
 •Islet Cell Tumors
• Hyperinsulinism (insulinomas)
• Hypergastrinemia
• Zollinger-Ellison syndrome- gastrinomas (A gastrinoma is a gastrin-
producing tumor usually located in the pancreas or the duodenal wall)
• Multiple endocrine neoplasias (MEN-1)