Partial 5 - Gastrointestinal Pathophysiology, PUD, ZE syndrome, Pancreatitis Flashcards
PUD is
Mucosal defect in the GI tract (gastric or duodenal) exposed to acid and pepsin secretion
Duodenal and Gastric ulcers are common at which ages
Duodenal 25-75 years
Gastric 55-65 years
Which type of ulcer has frequently pain that wakes them up at night
Duodenal ulcer patients (2/3)
In gastric ulcers is only 1/3
Differential diagnosis for epigastric pain
PIGGNUB: Pancreatitis Irritable bowel disease Gastroenteritis GERD Non-ulcer dyspesia/gastritis Ulcer disease Biliary colic or cholecystitis
Most common signs and symptoms of PUD
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
Other signs and symptoms of PUD
Dyspepsia (impaired digestion) including belching and bloating
Hematemesis (vomiting with blood) or melena (dark stools) with GI bleeding
Risk factors of PUD
H. pylori NSAIDs Coffee Ethanol Tobacco Severe physiologic stress (bruns, CNS trauma, surgery, severe medial illness) Steroids
Ulcers associated with H. pylori are often in the
Duodenum, often deep and there is less severe bleeding
Ulcers associated with NSAIDs are often in the
Stomach, superficial, more severe bleeding and sometimes asymptomatic
Diseases associated with increased risk of PUD
Hypersecretory states (ZE or MEN-I)
Cirrhosis
COPD
Renal failure
Most common cause of PUD
H. pylori
Complications of PUD
- 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
Gastrinomas (ZE syndrome) are derived from
Multipotential stem cells of endodermal origin
Gastrinomas arise mainly in
Small intestine (70% in duodenum) Pancreas
Duodenal vs pancreatic gastrinomas
Duodenal gastrinomas are small, multiple and they have less malignant potential than pancreatic gastrinomas
Signs and symptoms of ZE
- 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.
Diagnosis of ZE
- Fasting serum gastrin concentration
- Secretin stimulation test
- Gastric acid secretion studies
Treatment of ZE
- Proton-pump inhibitors
- Parietal cell vagotomy
- Octreotide (inhibits gastrin secretion by G-cells)
Most common sites of metastasis in ZE
Liver is the most common. Second most common is bone occuring in 7% of cases
Pancreatitis occur due to
Premature activation of pancreatic exocrine enzymes (trypsin, phospholipase A, and elastase)
Trypsin converts
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
Release of kallikrein and chymotrypsin results in
Increased capillary membrane permeability, leading to leakage of fluid into the interstitium and development of edema and relative hypovolemia
Which enzyme is the most harmful in terms of direct cell damage?
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.
Phospholipase A function in the presence of bile
Destroys phospholipids of cell membranes causing severe pancreatic and adipose tissue necrosis.
Lipase function
Lipase flows into damaged tissue and is absorbed into systemic circulation, resulting in fat necrosis of the pancreas and surrounding tissues
Causes of Acute pancreatitis
-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
Clinical Manifestation of Pancreatitis
- 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.
Abdominal Examination in Pancreatitis
- 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.
Diagnostic Evaluation in Pancreatitis
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).
Ranson’s criteria
(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.
Ranson’s criteria mortality rate
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
Complications of Acute Pancreatitis
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.
Treatment of Pancreatitis
- 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
Chronic Pancreatitis
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.
Chronic Pancreatitis is almost always associated with
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)
Most common cause of chronic pancreatitis in children
Cystic fibrosis
Three hypothesis of how alcohol can lead to chronic pancreatitis
- Ductal obstruction hypothesis
- Toxic metabolic hypothesis
- Necrosis fibrosis hypothesis
Mutations in genes encoding for chronic pancreatitis
- CFTR (cystic fibrosis trans-membrane conductance regulator)
- PRSS1 (cationic trypsinogen gene)
- SPINK1 (serine protease inhibitor Kazal type 1)
Mutations of CFTR gene leads to
Secretions of the pancreas becoming thick and thus leading to pancreatitis.
PRSS1 is the gene encoding for
Trypsin
SPINK1 encodes for a protein called
Trypsin inhibitor
Clinical manifestation of Chronic pancreatitis
- 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)
Complications of Chronic Pancreatitis
(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.
