The Pathology of Pancreas - PowerPoint PPT Presentation

About This Presentation
Title:

The Pathology of Pancreas

Description:

Title: The Pathology of Pancreas Subject: Pathology Author: ASCologlu Last modified by: idogan Created Date: 9/20/2000 6:31:25 AM Document presentation format – PowerPoint PPT presentation

Number of Views:487
Avg rating:3.0/5.0
Slides: 65
Provided by: ASC112
Category:

less

Transcript and Presenter's Notes

Title: The Pathology of Pancreas


1
The Pathology ofPancreas
2
Exocrine Component of Pancreas
3
  • The most significant disorders of the exocrine
    pancreas are
  • Congenital anomalies
  • Cystic fibrosis (Mucoviscidosis)
  • Pancreatitis (acute chronic)
  • Tumors

4
Congenital Anomalies
  • Agenesis
  • Aberrant (ectopic) pancreas
  • Stomach, duodenum, jejunum, Meckels
    diverticulum, ileum
  • Hypoplasia
  • endocrine and exocrine elements
  • Annular pancreas
  • the head of the pancreas may encircle the
    duodenum as a collar
  • cause subtotal duodenal obstruction
  • Ductal anomalies
  • Pancreas divisum ducts of Wirsung and of
    Santorini (accessory pancreatic duct) may both
    persist as totally separate structures, with
    separate duodenal orifices

5
Cystic Fibrosis (Mucoviscidosis)
  • Genetic pediatric disorder
  • autosomal recessive
  • the locus for the disease is chromosome 7q
  • Common (1/2500 births)
  • Often fatal in childhood and young adult life
  • This defect results in
  • (1) increased salt content of sweat
  • (2) decreased water content of respiratory,
    intestinal, and pancreatic exocrine secretion,
    leading to increased viscosity.

6
  • Cystic fibrosis is caused by
  • Lack of a membrane component essential to proper
    chloride transport across membranes of the
    mucus-producing exocrine glands and eccrine sweat
    glands in response to cAMP (Cyclic-Adenosine
    monophosphate)

7
  • Changes in the pancreas and mucous salivary
    glands
  • ducts plugged by viscous mucus
  • cysts" form behind the plugs
  • "fibrosis atrophy" ensues after years of
    obstruction
  • Manifestations
  • recurrent pulmonary infections leading to chronic
    lung disease
  • pancreatic insufficiency
  • steatorrhea
  • malnutrition
  • hepatic cirrhosis
  • intestinal obstruction
  • male infertility

8
  • The clinical syndrome is complex and reflects the
    underlying pathophysiology.
  • The bronchial epithelium
  • Lumens become plugged by thick mucus
  • Lung infections
  • Staph. aureus
  • Pseudomonas aeruginosa
  • Pneumonias
  • Lung abscesses
  • Bronchiectasis
  • Airway ulcers

9
  • The sweat glands
  • Perform normally, but chloride is not reabsorbed
    through the sweat ducts
  • These children's sweat is excessively salty
  • Salivary glands
  • Produce mucus (all but the parotid)
  • Some degree of plugging and atrophy
  • Bile ducts
  • Mucus plugs
  • Cirrhosis
  • Bowel
  • Obstruction due to thick mucus (meconium ileus)

10
  • The pancreatic ductal epithelium
  • Chloride secretion disorders
  • Plugged pancreatic ducts
  • Atrophy
  • Malabsorption
  • Vitamin deficiencies (vitamin A and K)

11
Pancreatitis
  • Acute pancreatitis
  • Mild form
  • Accompanied by edema and limited necrosis of
    pancreatic tissue
  • Severe form
  • acute hemorrhagic pancreatitis, or necrotizing
    pancreatitis,
  • extensive fat necrosis
  • hemorrhage into the parenchyma of the pancreas

12
Etiology
  • Metabolic
  • Alcohol
  • Hyperlipoproteinemia
  • Hypercalcemia
  • Drugs (glucocorticoids, pentamidine,
    azathioprine)
  • Mechanical
  • Gallstones (migrating)
  • Trauma
  • Surgery
  • Parasitic diseases
  • Vascular
  • Shock
  • Embolism
  • P. Nodosa
  • Infectious
  • Mumps
  • Coxsackievirus
  • Mycoplasma pneumonia
  • Hypercalcemia
  • Anatomic anomalies

13
  • Pathophysiology of acute pancreatitis
  • Autodigestion by inappropriately activated
    enzymes (trypsin) ?
  • Trypsin activates various digestive enzymes and,
    clotting and complement (see next slide)
  • Small vessel thrombosis
  • Obstruction (gallstones or alcohol associated
    concretions) increases ? intraductal pressure ?
    enzyme-rich interstitial fluid ? fat necrosis ...?

14
activates clotting and complement
15
  • ...? Fat Necrosis attracts neutrophils ? release
    cytokines ? cause interstitial edema ? impairs
    blood flow ?causes ischemia and acinar cell
    injury
  • Infections, drugs, trauma, shock? premature
    release of proenzymes and lysosomal hydrolases?
    acinar cell injury

16
  • Pancreas undergoes
  • proteolysis (proteases)
  • lipolysis (lipase)
  • eventually with hemorrhage (elastases damage
    vessels)
  • This produces considerable acute inflammation
  • neutrophils
  • edema
  • Alcohol ? reactivate chronic pancreatitis

17
  • Pathology
  • (1) Proteolytic destruction of pancreatic
    substance
  • (2) necrosis of blood vessels with subsequent
    hemorrhage
  • (3) necrosis of fat
  • (4) an accompanying inflammatory reaction
  • Very early stages
  • interstitial edema
  • Soon after
  • focal and confluent areas of frank necrosis
  • neutrophilic infiltration
  • interstitial hemorrhage
  • The most characteristic histologic lesions
  • focal areas of fat necrosis in the pancreatic and
    peripancreatic fat tissue

18
(No Transcript)
19
  • Distrophic
  • calcification
  • Amorphous basophilic calcium precipitates may be
    visible within the necrotic focus

20
Chronic Pancreatitis
  • The disease occurs in the same type of patient
    likely to develop acute pancreatitismost
    commonly
  • the middle-aged
  • male
  • Chronic alcoholism
  • Biliary tract disease
  • Alcohol ? reactivate chronic pancreatitis
  • Hypercalcemia (hyperparathyroidism)
  • Hyperlipidemia
  • Pancreas divisum (stenosis of the duodenal
    papilla).
  • Uncertain etiology
  • nonalcoholic tropical pancreatitis
  • familial hereditary pancreatitis

21
  • Macroscopy
  • Small, firm, white pancreas (partial or total)
  • Calcifications
  • Microscopy
  • Chronic inflammatory infiltrate (lymphocytes)
  • Loss of acinar cells
  • Dilated ducts (contain protein plugs)
  • Fibrosis

22
  • PANCREATIC CYSTS
  • PANCREATIC PSEUDOCYST
  • CONGENITAL CYSTS
  • NEOPLASTIC CYSTS
  • 1. SEROUS CYSTADENOMA
  • 2. MUCINOUS CYSTADENOMA CYSTADENOCARCINOMA

23
Tumors of the Exocrine Pancreas
  • Benign
  • Cystic Tumors
  • 1. SEROUS CYSTADENOMA
  • 2. MUCINOUS CYSTADENOMA
  • Malignant
  • Adenocarcinoma
  • 60 head
  • 15 body
  • 5 tail
  • 20 diffuse

24
Adenocarcinoma
  • Risk factors
  • (1) smoking
  • (2) exposure to chemicals (chemists and garage
    workers)
  • (3) hereditary pancreatitis
  • (4) consumption (abuse) of fats and meat
  • (5) partial gastrectomy

25
  • Location Findings
  • Head of the pancreas ? the ampulla of Vater ?
    obstructive biliary symptoms (early)
  • Body or tail of the pancreas ? grows silently ?
    invasion to adjacent structures ? metastatic
    dissemination ? obstructive biliary symptoms
    (late)

26
  • Grossly
  • Carcinomas of the head
  • may be fairly small mass lesions
  • may be totally inapparent on external examination
  • increased consistency and irregular nodularity
  • Carcinomas of the body or tail
  • up to 10 cm in diameter
  • gray-white/scirrhous
  • homogenous
  • infiltrates the lobular architecture
  • larger tumors invade the duodenum and common bile
    duct (biliary obstruction)
  • Microscopy
  • Poorly differentiated adenocarcinoma
  • Deeply infiltrative growth pattern
  • Dense stromal fibrosis
  • Perineural invasion
  • Mucus production

27
(No Transcript)
28
(No Transcript)
29
Endocrine Component of Pancreas
30
ß cells a cells
31
Islets of Langerhans
  • Cell Type ()
  • Beta (70)
  • Alpha (5-20)
  • Delta (5)
  • PP (1 - 2)
  • EC
  • D1

Hormone Insulin Glucagon Somatostatin Pancreatic
Polypeptide Serotonin VIP
32
Blood Glucose Various Hormones
?
  • Hormone
  • Insulin
  • Glucortocoids
  • Glucagon
  • Growth Hormone
  • Epinephrine

Action ? Glucose ? Glucose ? Glucose ? Glucose ?
Glucose
Diabetic Syndrome
33
Diabetes mellitus
  • Diabetes mellitus is a common chronic disease
    characterized by relative or absolute deficiency
    of insulin, resulting in glucose intolerance.
  • A chronic metabolism disorder of
  • carbohydrate
  • fat
  • protein
  • Characterized by
  • Polyuria, Polydypsia, Polyphagia
  • Absolute or relative insulin deficiency
  • hyperglycemia
  • glycosuria

34
(No Transcript)
35
  • Types of Diabetes Mellitus
  • Type I
  • Autoimmune and idiopathic there is an absolute
    insulin lack
  • Type II
  • Defects in insulin secretion, and/or a relative
    lack of insulin, and/or insulin resistance
  • Type III
  • Damage to the pancreas (pancreatitis, tumors,
    hemochromatosis, cystic fibrosis)
  • Type IV
  • Gestational diabetes

36
Primary Diabetes mellitus
  • Insulin-dependent diabetes mellitus (IDDM)
  • Type I diabetes
  • (juvenile-onset diabetes)
  • lt20 y/o
  • Normal Weight
  • ? Insulin
  • Islet cell abnormalities
  • Autoimmunity
  • Severe Insulin Deficiency
  • Ketoacidosis common
  • Noninsulin-dependent diabetes mellitus (NIDDM)
  • Type II diabetes
  • (adult-onset diabetes)
  • gt30 y/o
  • Obesity
  • N / ? Insulin
  • No islet cell abnormalities
  • Insulin Resistance
  • Relative Insulin Deficiency
  • Ketoacidosis rare

37
Picture of the Islet Cells
  • Type I
  • Insulitis Early
  • Atrophy, Fibrosis
  • Beta-Cell Depletion
  • Genetic Predisposition
  • 95 HLA DR3/DR4
  • Autoimmunity
  • T-Cell Mediated
  • Selective Islet Cells
  • Islet Cell Antibodies
  • Environmental
  • Coxsackie - B Virus (GAD)
  • Type II
  • No Insulitis
  • Focal Atrophy, Amyloid
  • Mild Beta-Cell Depletion
  • Genetic Susceptibility
  • 20-40 Concordance in First Degree Relatives
  • No HLA Linkage
  • Autoimmunity
  • None
  • Environmental
  • None

38
Pathogenesis of Type I DM
Environment Viral infections
Genetic HLA-DR3/DR4
Autoimmune Insulitis
ß cell Destruction
Severe Insulin deficiency
Type I DM
39
Insulitis Type I
40
(No Transcript)
41
Type II
  • Deranged Insulin Secretion
  • Increased Insulin Secretion
  • Delayed Insulin Secretion
  • Deficiency of Insulin Secretion
  • Obesity
  • 80 Obese
  • ? Insulin
  • Insulin Resistance
  • ? Number of Receptors
  • Postreceptor Defects
  • Reduced GLUTS
  • Amyloid
  • Accumulation

Glucose Transporters
42
Pathogenesis of Type II DM
Environment Obesity
ß cell defect Genetic
Insulin resistance
Abnormal Secretion
Relative Insulin Deficiency
ß cell exhaustion
IDDM
Type II DM
43
Loss of ß cells Amyloid deposits Hyalinization
Islets in Type II
44
Complications
  • Short term Complications (metabolic)
  • Hypoglycemia
  • Diabetic Ketoacidosis
  • Non Ketotic hyperosmolar diabetic coma
  • Lactic acidosis
  • Long term Complications (microangiopathic)
  • Angiopathy
  • Retinopathy
  • Nephropathy
  • Neurophathy

See PATHOPHYSIOLOGY_Long term Complications in
Diabetes Mellitus
45
Increased Intracellular Glucose - Polyol
Pathways Non-Insulin Requiring Cells Schwann
Cells ----------------? Neuropathy Retinal
Pericytes ----------? Retinal Microaneurysms Lens
---------------?Lens Opacities
Sorbitol
Sorbitol
Fructose Sorbitol
46
(No Transcript)
47
(No Transcript)
48
(No Transcript)
49
Other problems of Diabetics
  • Hepatic fatty change
  • Complications of pregnancy
  • Macrosomia (hyperglycemia, growth factor)
  • Birth defects (preventable by euglycemia through
    pregnancy)
  • Infections
  • Bacterial
  • Fungal (mucor, candida)
  • Gallstones
  • Cholesterol
  • Altered platelet function
  • Skin lesions
  • Diabetic xanthomas
  • lipid-laden macrophages
  • Necrobiosis
  • focal necrosis (dermis)
  • necrobiosis lipoidica diabeticorum

50
(No Transcript)
51
Diabetes Mellitus - Mortality
  • Myocardial Infarction
  • Renal Failure
  • Atherosclerotic Heart Disease
  • Cerebrovascular Accident (CVA)
  • Infection
  • Gangrene
  • Hypoglycemia/Ketoacidosis

52
Gestational Diabetes
  • Pathophysiologically type II DM
  • Pregnancy is a state of insulin resistance
  • Increased Insulin needs in pregnancy
  • Insulin release is enhanced in pregnancy ?
  • increased insulin ? hunger ? over eating
  • When the pregnancy is over and the insulin needs
    return to normal, the diabetes usually disappears.

53
Gestational Diabetes Complications
  • Fetal
  • macrosomia
  • neural tube defects
  • neonatal hypoglycemia
  • hypocalcemia
  • hyperbilirubinemia Neonatal Jaundice
  • birth trauma
  • childhood/adolescent obesity
  • Maternal
  • higher risk of hypertension
  • pre-eclampsia
  • infections
  • cesarean section
  • future diabetes

54
Macrosomia
55
Macrosomia
56
Endocrine tumors of Pancreas
57
Islet Cell Tumors
  • Clinical syndromes associated with hyperfunction
    of the islets of Langerhans
  • (1) Hyperinsulinism and hypoglycemia (insulinoma)
    caused by diffuse hyperplasia of the islets of
    Langerhans
  • (2) Zollinger-Ellison syndrome (gastrinoma)
  • caused by benign adenomas that occur singly or
    multiply
  • (3) Multiple Endocrine Neoplasia (malignant islet
    tumors)

58
Islet-cell adenoma
59
Insulinomas Beta cell tumors
  • Most common of islet cell tumors
  • Paroxysmal hypoglycemia (? Glucose
    ? Insulin)
  • CNS - confusion, unconsciousness
  • Relief with glucose administration
  • Massively obese patients
  • Whipple's triad
  • (1) low measured plasma glucose
  • (2) mental changes especially related to fasting
    or exercise
  • confusion
  • stupor
  • loss of consciousness
  • (3) attacks relieved by glucose administration

60
  • b-cell tumors inducing hyperinsulinism
  • 70 are solitary adenomas
  • 10 are multiple adenomas
  • 10 are hyperplasia
  • 10 are metastasizing
  • Macroscopy
  • encapsulated
  • firm
  • yellow-brown nodules
  • Histology
  • cords and nests of well-differentiated beta cells

61
Insulinoma
62
Zollinger-Ellison Syndrome (Gastrinoma)
  • G-cell tumors
  • Gastrin Secretory Cell
  • Most common in the pancreas
  • 10 to 15 in the duodenum
  • 60 of gastrinomas are malignant
  • Striking gastric hypersecretion
  • A syndrome of
  • multiple bleeding ulcers
  • diarrhea (malabsorption)
  • Ulcers
  • Stomach
  • Duodenum (first and second portions)

63
(No Transcript)
64
Islet cell tumors (rare ones)
  • Alpha-two cell tumors (glucagonoma)
  • mild diabetes
  • sore tongue
  • necrolytic migratory erythema
  • Delta-cell tumors (somatostatinoma)
  • diabetes mellitus
  • cholelithiasis
  • steatorrhea
  • hypochlorhydria
  • VIPoma (diarrheogenic islet cell tumor)
  • watery diarrhea
  • hypokalemia
  • achlorhydria
Write a Comment
User Comments (0)
About PowerShow.com