Partial 5 - Gastrointestinal Pathophysiology, PUD, ZE syndrome, Pancreatitis

Question 1

PUD is

Answer 1

Mucosal defect in the GI tract (gastric or duodenal) exposed to acid and pepsin secretion

Question 2

Duodenal and Gastric ulcers are common at which ages

Answer 2

Duodenal 25-75 years

Gastric 55-65 years

Question 3

Which type of ulcer has frequently pain that wakes them up at night

Answer 3

Duodenal ulcer patients (2/3)

In gastric ulcers is only 1/3

Question 4

Differential diagnosis for epigastric pain

Answer 4

PIGGNUB:
Pancreatitis
Irritable bowel disease
Gastroenteritis
GERD 
Non-ulcer dyspesia/gastritis
Ulcer disease
Biliary colic or cholecystitis

Question 5

Most common signs and symptoms of PUD

Answer 5

Epigastric pain and is described as gnawing or burning pain which may radiate to the back and pain occurs 1-3 hours after meals or at night. Pain is relieved by food, antacids in duodenal ulcers, or vomiting in gastric ulcers

Question 6

Other signs and symptoms of PUD

Answer 6

Dyspepsia (impaired digestion) including belching and bloating
Hematemesis (vomiting with blood) or melena (dark stools) with GI bleeding

Question 7

Risk factors of PUD

Answer 7

H. pylori
NSAIDs
Coffee
Ethanol
Tobacco 
Severe physiologic stress (bruns, CNS trauma, surgery, severe medial illness)
Steroids

Question 8

Ulcers associated with H. pylori are often in the

Answer 8

Duodenum, often deep and there is less severe bleeding

Question 9

Ulcers associated with NSAIDs are often in the

Answer 9

Stomach, superficial, more severe bleeding and sometimes asymptomatic

Question 10

Diseases associated with increased risk of PUD

Answer 10

Hypersecretory states (ZE or MEN-I)
Cirrhosis
COPD
Renal failure

Question 11

Most common cause of PUD

Answer 11

H. pylori

Question 12

Complications of PUD

Answer 12

• Bleeding which may lead to hemorrhagic shock.
• Perforation which leads to peritonitis.
• Pyloric obstruction due to edema, spasm, or contraction of scar tissue and interference with the free passage of gastric contents through the pylorus
• Iron deficiency with microcytic anemia, which is characterized by fatigue and dyspnea
• Malignant transformation

Question 13

Gastrinomas (ZE syndrome) are derived from

Answer 13

Multipotential stem cells of endodermal origin

Question 14

Gastrinomas arise mainly in

Answer 14

Small intestine (70% in duodenum)
Pancreas

Question 15

Duodenal vs pancreatic gastrinomas

Answer 15

Duodenal gastrinomas are small, multiple and they have less malignant potential than pancreatic gastrinomas

Question 16

Signs and symptoms of ZE

Answer 16

• Peptic ulcers are present in 90% of patients with ZE
• Diarrhea (due to acid hypersecretion and volume overload)
• Steatorrhea (pancreatic bicarbonate secretion is inactivated by low pH + pancreatic enzymes are inactivated)
• Heartburn (44%)
• Weight loss (17%)
• GI bleeding (25%)
• Patients may also present with coughing.

Question 17

Diagnosis of ZE

Answer 17

• Fasting serum gastrin concentration
• Secretin stimulation test
• Gastric acid secretion studies

Question 18

Treatment of ZE

Answer 18

• Proton-pump inhibitors
• Parietal cell vagotomy
• Octreotide (inhibits gastrin secretion by G-cells)

Question 19

Most common sites of metastasis in ZE

Answer 19

Liver is the most common. Second most common is bone occuring in 7% of cases

Question 20

Pancreatitis occur due to

Answer 20

Premature activation of pancreatic exocrine enzymes (trypsin, phospholipase A, and elastase)

Question 21

Trypsin converts

Answer 21

Prekallikrein to its activated form, this sparking the kinin system, and, by activating factor XII (Hagemann factor), also sets in motion the clotting and complement systems

Question 22

Release of kallikrein and chymotrypsin results in

Answer 22

Increased capillary membrane permeability, leading to leakage of fluid into the interstitium and development of edema and relative hypovolemia

Question 23

Which enzyme is the most harmful in terms of direct cell damage?

Answer 23

Elastase is the most harmful in terms of direct cell damage and causes dissolution of the elastic fibers of blood vessels and cuts, leading to hemorrhage.

Question 24

Phospholipase A function in the presence of bile

Answer 24

Destroys phospholipids of cell membranes causing severe pancreatic and adipose tissue necrosis.

Question 25

Lipase function

Answer 25

Lipase flows into damaged tissue and is absorbed into systemic circulation, resulting in fat necrosis of the pancreas and surrounding tissues

Question 26

Causes of Acute pancreatitis

Answer 26

-Ethanol abuse Biliary diseases: -Gallstones, Choledocholithiasis, Biliary sludge, Microlithiasis Mechanical/structural injury: -Sphincter of Oddi dysfunction, Pancreatic divisum, Trauma, Postendoscopic retrograde cholangiopancreatography, Pancreatic malignancy, PUD, IBD Metabolic: -Hypertriglyceridemia, Hypercalcemia Infectious: -Viral (Mumps), Bacterial, Parasitic Vascular: -Vasculitis - Genetic predisposition - Idiopathic

Question 27

Clinical Manifestation of Pancreatitis

Answer 27

- It is characterized by upper abdominal pain rapidly increasing in severity and often within 60 minutes - Epigastric pain - Right-sided pain - Diffuse abdominal pain with radiation to back, patient preferring to sit and lean, - Fever - Hypovolemic shock and tachycardia. We also observe pseudocysts, and Jaundice may also occur.

Question 28

Abdominal Examination in Pancreatitis

Answer 28

- Decreased or absent bowel sounds - Abdominal tenderness - Guarding (muscle defences of inflamed organ) - Palpable mass in epigastric area - Biliary colic (pain due to intermittent blockage of bile duct) - Jaundice if there`s obstruction of the bile duct - Cullen`s sign (superficial edema/ bruising in subcutaneous fatty tissue around the umbilicus) - Grey turner`s sign (bruising of flank region, between last rib and top of the hip) - Abdominal tympany (drum-like sound that is heard when tapping the abdomen sharply due to gas in the abdomen.

Question 29

Diagnostic Evaluation in Pancreatitis

Answer 29

Serum amylase and lipase elevated 3-5 times normal, as well as urine amylase and lipase increased for 1-2 weeks. Serum amylase may be normal in patients with pancreatitis related to alcohol abuse or hypertriglyceremia Levels greater than five times the top normal value should be expected in patients with renal failure because amylase is cleared by the kidneys A lipase to amylase ratio of greater than 2 is usually evident with pancreatitis related to alcohol abuse Decreased serum calcium due to formation of calcium soaps. Elevated serum bilirubin, AST, ALT, LD, and alkaline phosphatase. Pancreatitis due to gallstones usually lead to elevation of AST, ALT, and lactate dehydrogenase Abdominal X-rays and CT showing pleural effusions and bowel dilation Hemoconcentration is due to third space fluid loss (Edema, patients with acute pancreatitis may have fluid shifts of 4-12L into retroperitoneal space and peritoneal cavity due to inflammation).

Question 30

Ranson's criteria

Answer 30

``` (1) On admission; (A) age older than 55 (B) WBC more than 16000 (C) Serum glucose more than 200 (D) serum LD more than 350 (E) AST more than 250. ``` (2) During initial 48 hours after admission; (A) 10% decrease in Hct (B) BUN increase more than 5 (C) Serum calcium more than 8 (D) Base deficit more than 4 (E) PaO2 less than 60, and estimated fluid sequestration more than 6 liters.

Question 31

Ranson's criteria mortality rate

Answer 31

1% mortality for patients with fewer than three of Ranson`s criteria 16% mortality for patients with three or four criteria 40% mortality for those with five or six criteria 100% mortality for patients with seven or eight criteria

Question 32

Complications of Acute Pancreatitis

Answer 32

Pulmonary: -Atelectasis, Pleural effusions, ARDS Cardiovascular: -Cardiogenic shock Neurologic: -Pancreatic encephalopathy Metabolic: -Metabolic acidosis, Hypocalcemia, Altered glucose metabolism – hyperglycemia Hematologic: -DIC, GI bleeding Renal: -Prerenal failure.

Question 33

Treatment of Pancreatitis

Answer 33

- IV replacement fluids, proteins and electrolytes - Somatostatin to decrease pancreatic secretion - Anticholinergic drugs can also be used - Demerol is used for pain over morphine - Pneumatic compressions are used

Question 34

Chronic Pancreatitis

Answer 34

is when there is irreversible damage to the pancreas with histologic evidence of inflammation, fibrosis, calcification, and destruction of exocrine and endocrine tissues of the pancreas.

Question 35

Chronic Pancreatitis is almost always associated with

Answer 35

Alcoholism, but can also be associated with: - Trauma - Cystic fibrosis - Autoimmune pancreatitis - Tropical pancreatitis - Long-standing pancreatic obstruction - Hereditary pancreatitis due to mutations in the pancreatic trypsinogen gene or the SPINK1 (serine protease inhibitor Kazal type 1 - Gene encoding trypsinogen inhibitor (PRSS1)

Question 36

Most common cause of chronic pancreatitis in children

Answer 36

Cystic fibrosis

Question 37

Three hypothesis of how alcohol can lead to chronic pancreatitis

Answer 37

- Ductal obstruction hypothesis - Toxic metabolic hypothesis - Necrosis fibrosis hypothesis

Question 38

Mutations in genes encoding for chronic pancreatitis

Answer 38

- CFTR (cystic fibrosis trans-membrane conductance regulator) - PRSS1 (cationic trypsinogen gene) - SPINK1 (serine protease inhibitor Kazal type 1)

Question 39

Mutations of CFTR gene leads to

Answer 39

Secretions of the pancreas becoming thick and thus leading to pancreatitis.

Question 40

PRSS1 is the gene encoding for

Answer 40

Trypsin

Question 41

SPINK1 encodes for a protein called

Answer 41

Trypsin inhibitor

Question 42

Clinical manifestation of Chronic pancreatitis

Answer 42

- Abdominal and back pain - Progressive disability - Steatorrhea due to pancreatic insufficiency and lipase deficiency - Fat malabsorption may be accompanied by a deficiency of fat-soluble vitamins and can thus lead to such conditions as night blindness (vitamin A deficiency) and osteomalacia (vitamin D deficiency) - Pseudocyst are seen and diabetes mellitus occurs (due to destruction of endocrine pancreas)

Question 43

Complications of Chronic Pancreatitis

Answer 43

(1) Cobalamin malabsorption due to excess binding by cobalamin binding proteins other than intrinsic factor which were degraded by pancreatic enzymes (2) DM, but end organ damages of DM and DKA are rare (3) Non DM retinopathy due to vitamin A and Zn deficiencies (4) Pleural, peritoneal and pericardial effusions with high amylase (5) GI bleeding (splenic vein thrombosis) (6) Cholestasis, icterus, cholangitis, and biliary cirrhosis (7) Fistula, which can be internal or external (8) Subcutaneous fat necrosis, with tender red nodules on the shins (9) Pseudocyst and obstruction (10) Pancreatic carcinoma (4% life time risk) (11) Narcotic addiction due to pain.