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Gastrointestinal System > The Pathology of the Pancreas > Flashcards

The Pathology of the Pancreas Flashcards

1
Q

Which portion of the pancreas secretes digestive enzymes into the duodenum?

A

The exocrine pancreas

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2
Q

What are the parts of the exocrine pancreas?

A

Acinar and centroacinar (ductal) cells with associated connective tissue, vessels, and nerves

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3
Q

What % of the pancreatic mass is exocrine?

A

More than 95%

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4
Q

Where do the hormones of the endocrine part of the pancreas empty?

A

Straight into the bloodstream

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5
Q

What is agenesis of the pancreas?

A

It is an extremely rare congenital condition that results from defective pancreatic formation

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6
Q

What is the pathogenesis of agenesis of the pancreas?

A

Mutation of the PDX1 gene, located on chromosomal locus 13q12.1

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7
Q

What are the different types of agenesis?

A

Partial and complete agenesis

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8
Q

What is partial agenesis?

A

The pancreas body is of varied size, a remnant of the accessory duct exists and the minor papilla is present

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9
Q

What is complete agenesis?

A

The neck, body, and tail of the pancreas are absent, as well as the accessory duct and the minor duodenal papilla

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10
Q

What is the most common congenital abnormality?

A

Pancreas divisum (3 to 10%)

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11
Q

What is pancreas divisum? What is the result of it?

A

Dorsal and ventral pancreatic ducts fail to fuse. Thus, the main pancreatic duct only drains a small portion of the head of the gland

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12
Q

Where does the bulk of the pancreas drain into in the pancreas divisum?

A

Drains through the minor sphincter, which is a narrow opening

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13
Q

What can pancreas divisum lead to?

A

Acute/chronic pancreatitis

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14
Q

What is annular pancreas?

A

When a ring of pancreatic tissue completely encircles the duodenum

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15
Q

What is the risk associated with an annular pancreas?

A

Duodenum obstruction

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16
Q

What is an ectopic pancreas?

A

Heterotopic pancreatic tissue occurs in 2 to 15% of the population

Pancreatic tissue lies outside and separates into the pancreatic gland

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17
Q

What are the common sites where pancreatic tissue can be found in the ectopic pancreas?

A

Stomach & duodenum
Jejunum
Ileum

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18
Q

What is a congenital cyst?

A

Faulty development of pancreatic duct

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19
Q

What is the morphology of the congenital cyst?

A

Unilocular cyst (up to 5cm)
Lined by either uniform cuboidal or flattened epithelium
Enclosed in a thin, fibrous capsule

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20
Q

What is pancreatitis?

A

Inflammatory disorders of the pancreas

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21
Q

What are the congenital abnormalities, involving the pancreas?

A

Ectopic Pancreas
Congenital Cyst
Annular Pancreas
Pancreas divisum
Agenesis

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22
Q

What is acute pancreatitis?

A

Inflammation and hemorrhage but function can return to normal if the underlying cause of inflammation is removed

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23
Q

What is chronic pancreatitis?

A

Inflammatory disorder with irreversible destruction of exocrine pancreatic parenchyma

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24
Q

How does acute pancreatitis occur?

A

It is due to the autodigestion of pancreatic parenchyma by pancreatic enzymes (premature activation of trypsin leads to activation of other pancreatic enzymes)

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25
Q

What is the incidence of acute pancreatitis?

A

10 to 20% per 100000

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26
Q

What is the male-female ratio for acute pancreaitis?

A

1:3 with gallstones
6:1 with alcoholism

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27
Q

What are the causes of acute pancreatitis ?

A

Non-traumatic
Traumatic
Idiopathic

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28
Q

What are the non-traumatic causes of acute pancreatitis?

A

Biliary tract disease
Alcohol
Viral Infections (EBV, CMV)
Hyperlipidemia
Hyperparathyroidism

75% of cases

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29
Q

What are the traumatic causes of acute pancreatitis?

A

Operative trauma
Endoscopic procedure with fye injection

5%

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30
Q

What is the % of cases of acute pancreatitis due to idiopathic causes?

A

20%

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31
Q

What is the pathogenesis of acute pancreatitis?

A

This can occur as a result of inappropriate activation of pancreatic enzymes

This leads to autodigestion of the pancreas and triggers an inflammatory cascade

Can result in necrosis both within the pancreas itself and extra-pancreatic adipose tissue

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32
Q

What can cause acinar cell injury? How does that lead to acute pancreatitis?

A

Viral infections, drugs and direct trauma
Direct damage to acinar cells

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33
Q

What can cause duct obstruction and how does it lead to acute pancreatitis?

A

Gallstones and Chronic alcoholism

  1. Blocks ductal flow
  2. Increases intraductal pressure
  3. Allows accumulation of enzyme-rich intestinal fluid
  4. Injured tissues, periacinar myofibroblasts, and leukocytes then release pro-inflammatory cytokines
  5. Promote local inflammation and interstitial edema through a leaky microvasculature
  6. Edema further compromises local blood flow
  7. Vascular insufficiency and ischemic injury to acinar cells
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34
Q

What can cause defective intracellular transport and how does it lead to acute pancreatitis?

A

Metabolic injury

  1. Pancreatic proenzyme and lysosomal hydrolases become packaged together
  2. Results in proenzyme activation, lysosomal rupture, and local release of activated enzymes
  3. Acinar cell injury
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35
Q

What occurs in normal acinar cells?

A

Digestive enzymes intended for zymogen granules and hydrolytic enzymes destined for lysosomes are transported in discrete pathways after synthesis in the endoplasmic reticulum

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36
Q

What are the basic alteration in the morphology of acute pancreatitis? (5)

A
  1. Microvascular leakage due to edema
  2. Necrosis of fat by lipases
  3. Acute inflammatory reaction
  4. Proteolytic destruction of pancreatic parenchyma
  5. Destruction of blood vessels leading to intestinal hemorrhage
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37
Q

What is the morphology in mild acute pancreatitis?

A

Acinar cell necrosis, intense acute inflammation and foci of necrotic adipocytes

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38
Q

What does the fat necrosis result from in mild acute pancreatitis?

A

Enzymatic destruction of fat cells, released faty acids combine with calcium to form insoluble salts that precipitate in situ

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39
Q

What is the pathogenesis of severe acute pancreatitis?

A

Becrisus of pancreatic tissue affects acinar, ductal tissues and islets of Langerhans

That causes vascular damage

Which causes hemorrhage into the parenchyma of the pancreas

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40
Q

What are the gross-features of severe acute pancreatitis?

A

The pancreas exhibits red black hemorrhagic areas interspersed with foci of yellow-white chalky fat necrosis

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41
Q

What are the most common signs and symptoms of acute pancreatitis?

A

Severe epigastric pain RADIATING to the back
Nausea, vomiting, diarrhea and loss of appetite
Fever and chills
Hemodynamic instability

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42
Q

What are the signs and symptoms in severe cases of acute pancreatitis?

A

Tenderness, guarding and rebound

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43
Q

What are the signs of acute pancreatitis which are less common?

A

Grey-Turner’s sign (hemorrhagic discolouration of the flanks)
Cullen’s sign (Hemorrhagic discolouration of the umbilicus)

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44
Q

What is the CT apperance of Grade A acute pancreatitis ?

A

Normal CT

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45
Q

What is the CT apperance of Grade B acute pancreatitis ?

A

Focal or diffuse enlargement of the pancreas

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46
Q

What is the CT apperance of Grade C acute pancreatitis?

A

Pancreatic gland abnormalities and peripancreatic inflammation

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47
Q

What is the CT apperance of Grade D acute pancreatitis ?

A

Fluid collection in a single location

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48
Q

What is the CT apperance of Grade E acute pancreatitis ?

A

Two or more fluid collections and/or gas bubbles in or adjacent to pancreas

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49
Q

What is the necrosis score?

A

No necrosis = 0
0 to 30% = 2
30 to 50% = 4
Over 50% = 6

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50
Q

What are the complication of acute pancreatitis?

A

Fluid collections associated with intestitial edematous pancreatitis

Fluid collections associated with necrotsising pancreatitis

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51
Q

What is pancreatic fluid collection?

A

In the first 4 weeks; non - encupasulated pancreatic fluid collections

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52
Q

What are pseudocysts?

A

Develop after 4 weeks; encapsulated peripancreatic or remote fluid collections

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53
Q

What is acute necrotic collection?

A

In the first 4 weeks; non-encapsulated heterogenous non-liquefied material

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54
Q

What is walled-off necrosis?

A

Develop after 4 weeks; encapsulated heterogenous non-liquefied material

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55
Q

What is chronic pancreatitis?

A

Long standing inflmmation of the pancreas

56
Q

What is chronic pancreatitis characterised by?

A

Irreversible dectruction of the exocrine pancraes
Loss of islets
Loss of pancreatic function

57
Q

What is the prevelance of chronic pancreatitis?

A

Up to 5% of the US population

58
Q

What are the causes of chronic pancreatitis?

A

Most of the causes of acute pancreatitis can lead to chronic if not resolved

59
Q

What often characterises chronic pancreatitis?

A

Intermittent acute attacks and followed by periods of quiesece that suggests it may evolve from repeated bouts of acute pancreatitis

60
Q

What are examples of the causes of chronic pancreatitis?

A

Heavy alcohol consumption
Chronic duct obstruction
Trauma
Hyperparathyroidism
Hypertriglyceridemia
Autoimmune pancreatitis
Tropical pancreatitis
Hereditary pancreatitis
Idiopathic

61
Q

What are the type of autoimmune pancreatitis?

A

Type 1: IgG4 related
Type 2: also called idiopathic duct-centric pancreatitis

62
Q

What happens with type 1 AIP?

A

IgG4 attack pancreas, bile duct, liver, kidney and lymph nodes

63
Q

What happens with type 2 AIP?

A

Associated with inflammatory bowel disease

64
Q

What is hereditary pancreatitis?

A

Mutations in the pancreatic trypsinogen gene (PRRS1) or SPINK1 gene encoding a trypsin inhibitor

65
Q

What are the several hypotheses about the pathogenesis of chronic pancreatitis?

A
  1. Ductal Obstruction by Concentrations
  2. Toxic Metabolic
  3. Oxidative Stress
  4. Inappropriate activation of pancreatic enzymes due to mutations affecting genes
66
Q

What is the ductal obstruction by concentrations hypothesis?

A

Presence of inciting agents
Increase the protein concentration of pancreatic sceretion
These proteins can form ductal plugs

67
Q

What is the toxic metabolic hypothesis?

A

Toxins, including alcohol and its metabolites, can exert a direct toxic effect on acinar cells.

68
Q

What can the direct toxic effect of alcohol and its metabolites on acinar cells lead to?

A

Lipid accumulation
Acinar cell loss
Eventually parenchyma loss

69
Q

What is the oxidative stress hypothesis?

A

Stress may generate free radicals in acinar cells –> leading to membrane damage

70
Q

What does the membrane damage of the oxidative stress lead to?

A

Subsequent expression of chemokine (IL-8), which recruits mononuclear inflammatory cells

71
Q

What does oxidative stress also promote?

A

The fusion of lysosomes and zymogen granules –> Leads to acinar cell necrosis, inflammation and fibrosis

72
Q

What causes the inappropriate activation of pancreatic enzymes due to mutations affecting genes?

A

Mutations in pancreatic trypsinogen gene or the SPINK1 gene encoding a trypsin inhibitor

73
Q

Which profibrogenic cytokines are secreted in chronic pancreatitis and how?

A

Transforming growth factor B
Connective tissue growth factor
Platelet-derived growth factors

Secreted by infiltrating immune cells such as macrophages

74
Q

What do the profibrogenic cytokines in chronic pancreatitis cause?

A

They induce the activation and proliferation of pericinar myofibroblasts, which deposit collagen and give rise to fibrosis

75
Q

What is the macroscopic morphology of chronic pancreatitis?

A

Calcifying pancreatitis

76
Q

What is the most common type of chronic pancreatitis?

A

Calcifying pancreatitis

77
Q

What is calcifying pancreatitis associated with?

A

Chronic alcoholism

78
Q

What is the microscopic morphology of chronic pancreatitis?

A

Parenchymal fibrosis
Reduced number and size of acini with relative sparing of the islets
Acinar loss
Variable dilation of the pancreatic duct with concretions
Chronic inflammatory infiltrate around lobules and ducts

79
Q

What are the clinical features of the chronic pancreatitis?

A

Repeated bouts of jaundice, vague indigestion, persistent or recurrent abdominal and back pain

Mild pain and modest elevations of serum amylase

Visualization of calcifications within the pancreas by CT or ultrasound

80
Q

What are the complications of chronic pancreatitis? (7)

A

Pseudocyst
Pancreatic ascites
Pancreatic fistula
Weight loss/malabsorption
Pancreatic carcinoma
Common bile duct obstruction
Splenic/portal vein thrombosis

81
Q

What are the two categories of pancreatic neoplasms?

A

Neoplasms of exocrine pancreas
Neoplasms of endocrine pancreas

82
Q

What are the examples of neoplasms of exocrine pancreas?

A

Ductal adenocarcinoma
Cystic neoplasm

83
Q

What are the different kinds of cystic neoplams?

A

Mucinous
Serous
Intraductal Papillary Mucinous Neoplasms

84
Q

What is the incidence of neoplasms of the endocrine pancreas?

A

Rare

85
Q

What are examples of neoplasms of the endocrine pancreas?

A

Neuroendocrine tumors
Islet cell tumors

86
Q

What is the most common cystic neoplasm type?

A

Mucinous Cystic Neoplasm

87
Q

Who is most commonly affected by mucinous cystic neoplasms?

A

Young women, men are rarely affected

88
Q

Where are mucinous cystic neoplsasms found?

A

Typically found in the body and the tail of the pancreas.

89
Q

What is the microscopy of the mucinous cystic neoplasms?

A

Multiocular
Cystic are lined by a columnar mucinous epithelium with an associated densely cellular storm
Cystic spaces filled with thick, tenacious mucus

90
Q

What is the cross section of mucinous cystic neoplams?

A

Eggshell calcification, larger tumor size, mural nodule on cross sectional imaging

91
Q

What is the standard treatment for mucinous cystic neoplasms?

A

Pancreatic resection

92
Q

What is a serous cystic neoplasm??

A

A predilection for the body and tail of the pancreas

93
Q

What is the female-to-male ratio for serous cystic neoplasm?

A

3:1

94
Q

What are the main signs of serous cystic neoplasm?

A

Seventh decade with vague abdominal pain and less frequently with weigh loss and obstructive jaundice

95
Q

Which gene is serous cystic neoplasm associated with?

A

Inactivation of VHL tumor suppressor gene

96
Q

What is the range of size of serous cystic neoplasms?

A

1 to 25cm:
Large > 4 or rapidly growing
Small < 4

97
Q

What is the treatment for large serous cystic neoplasms?

A

Resection

98
Q

What is the treatment for small serous cystic neoplasms?

A

Asymptomatic thus can only be observed

99
Q

What do serous cystic neoplasms look like microscopiocally?

A

Multiloculated, glycogen rich small cysts

100
Q

What is the cross-section of serous cystic neoplasms like ?

A

Composed of glycogen-rich cuboidal cells surrounding small cysts containing clear, straw-colored fluid

101
Q

What are intraductal papillary mucinous neoplasms? (IPMN)

A

Dilated pancreatic duct lined by neoplastic mucinous epithelium and filled with mucous

102
Q

What are the differences between the intraductal papillary mucinous neoplasms and the mucinous cystic ones?

A

IPMN are:
More frequently in men than in women
Involve the head of the pancreas

103
Q

What is the morphology of IPMN?

A

The main pancreatic duct, or one of its branch ducts, lacks the cellular stroma seen in mucinous

104
Q

What is the risk of malignancy invasion with IPMN?

A

10 to 20%

105
Q

What is the pathogenesis of IPMN?

A

Mutations f GNAS on chromosome 20q13
Activation of G proteins –> intracellular cascade that promotes cell proliferation

106
Q

What is the function of the GNAS gene?

A

Encodes for the alpha subunit of a stimulatory G-protein, Gs

107
Q

What is the incidence of pancreatic ductal adenocarcinoma?

A

9th most common cancer diagnosed
3rd in cancer deaths
Men> women
African Americans have a slightly higher risk
Low incidence in Middle East and India

108
Q

What is the mean age of diagnosis for PDAC?

A

72 years of age

109
Q

What are the risk factors for PDAC?

A

Smoking
Chronic pancreatitis
Diabetes melitus
Inherited genetic defect (BRAC2)
Infections (HBV, H.pylori)

110
Q

What is the sequential pathway that has been noted in the development of PDAC?

A

From pancreatic intraepithelial neoplasia (PanIN) to invasive cancer

111
Q

How are PanIN characterized?

A

Mucinous epithelium replacing the normal lining of the ducts

112
Q

What are the grades PanINs are categorized in?

A

Increasing cytoarchitectural and genetic abnormalities

113
Q

What are some early events in the pathogenesis of PDAC?

A

Telomere shortening and mutational activation of the KRAS oncogene

114
Q

What happens later in the sequence of neoplastic progression in PDAC?

A

There is mutation inactivation or deletion of the tumor suppressor gene

115
Q

What are examples of genes that are deleted in the progression of PDAC?

A

p16/CDKN2A
p53
MAD4/DPC-4

116
Q

What is the cytoarchitecture of PainIN-1A?

A

Presence of columnar, mucin-producing ductal epithelium

117
Q

What is the genetic abnormality of PanIN-1A?

A

Telomere shortening
Mutation of KRAS

118
Q

What is the cytoarchitecture of PanIN-1B?

A

The development of papillary architecture

119
Q

What is the cytoarchitecture of PanIN-2?

A

Evidence of nuclear atypia

120
Q

What are the genetic abnormalities of PanIN-2?

A

Inactivation of p16

121
Q

What is PanIN-3 considered as?

A

Carcinoma in situ

122
Q

What is the cytoarchitecture of PanIN-3?

A

Marked cytologic atypia, complete loss of polarity

123
Q

What are the genetic abnormalities of PanIN-3?

A

Inactivation of p53, SMAD4 and BRAC2

124
Q

Where do pancreatic cancers arise in and what is their percentage?

A

Head of gland (60%)
The body (15%)
The tail (5%)
Entire organ (20%)

125
Q

What is the gross section of pancreatic cancers?

A

Hard, grey-white, stellate & poorly defined masses

126
Q

What is the histology of pancreatic cancers?

A

Highly invasive
Desmoplasia
Poorly formed glands in a densely fibrotic stroma

127
Q

What is the meaning of desmosplasia?

A

It involves fibroblasts, lymphocytes and extracellular matrix

128
Q

What are the frequent signs of pancreatic carcinoma ?

A

Abdominal pain
Anorexia, weight loss & malaise (manifestations of advanced disease)
Jaundice (lesions of the pancreatic head only)

129
Q

What are some infrequent signs and symptoms of pancreatic carcinoma?

A

Glucose intolerance
Palpable gallbladder with painless jaundice
Migratory thrombophlebitis
GI hemorrhage
Splenomegaly

130
Q

What is Palpable gallbladder with painless jaundice known as?

A

Courvoisier’s sign

131
Q

What is Migratory thrombophlebitis known as?

A

Trousseau’s sign

132
Q

What are the serum levels like in pancreatic carcinoma?

A

Serum levels of carcinoembryonic and CA19-9 antigens are elevtaed

133
Q

Are the carcinoembryonic and CA19-9 markers specific?

A

Non specific nor sensitive

134
Q

What is the prognosis of pancreatic carcinoma?

A

Locally invasive
Distant metastasis

135
Q

Where can pancreatic carcinoma spread to?

A

regional lymph nodes

136
Q

What do pancreatic carcinomas directly invade?

A

Retroperitoneal structures

Gastrointestinal System (28 decks)

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