Pancreas Pathophys Flashcards
1
Q
chronic pancreatitis
A
- Chronic inflammatory changes that lead to:
- Parenchymal fibrosis
- Ductal dilation: dilation of the pancreatic ductal system
- Exocrine insufficiency
- Malabsorption
- Steatorrhea
- Clinically these patients may have malabsorption and steatorrhea because of exocrine insufficiency
- *You need to lose 95% of your pancreatic parenchyma in order to have steatorrhea and exocrine insufficiency, and clinically manifest this way.
- Endocrine insufficiency
- These patients can have endocrine insufficiency as well. They can develop diabetes.
- Pain
- Intermittent or long-lasting
One of the key characteristics that is frustrating for patients is pain which can be intermittent, or constant or remitting. It’s a very heterogenous presentation
2
Q
treatment of gallstones
A
cholecystectomy
- For patients with gallstone disease as the etiology for pancreatitis (which is the #1 cause in the world and #2 in the USA), the definitive treatment is cholecystectomy (removal of the gallbladder)
- It is the definitive treatment but it is generally not the acute treatment for pancreatitis. When someone comes in with pancreatitis this is not the first thing you do, though it is the definitive treatment.
3
Q
pancreatic cancer on the body and tail
A
- If you have cancer in the body or tail:
- It is a much less specific symptom complex. You have pain, weight loss, and it is diagnosed later so the tumors tend to be larger.
- There are a number of biochemical markers that are useful but not 100% specific or sensitive. The classic one is CA19-9, which can be elevated in pancreatic cancer. (But, not all cancers have elevated markers.)
4
Q
A
pancreatic necrosis
- Somewhere over here (*) there is a transition
- This is an IV contrast study: the aorta is bright, meaning that this is an IV enhanced contrast study
- So, the head of the pancreas lights up well and the tail doesn’t. The tail part is necrotic. So that actually predicts mortality as well
- (So just be familiar with what the standard interstitial pancreatitis and the less common necrotic pancreatitis looks like)
5
Q
chronic pancreatitis mechanism
A
- Mechanism
- Obstruction of pancreatic duct (pressure)
- The mechanism for this is really not clear. If you have obstruction of the pancreatic duct from strictures or fibrosis or stones (you can actually get stones in the pancreatic duct), maybe there is a pressure phenomenon that mediates the pain.
- Increased parenchymal pressure
- pH/ischemia
- Local ischemia and acidosis may be at play. This is very interesting but controversial
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6
Q
the misdirection of proenzymes
A
•There is a general category which includes the misdirection of proenzymes (zymogens). Instead of directing them to secretion, they are misdirected to lysosomes within the cell where they are prematurely activated to the active enzyme within the cell and lead to an autolytic destruction of the pancreas.
7
Q
A
pancreatic pseudocyst
8
Q
blood supply of the head and uncinate process of the pancreas?
A
celiac + SMA branches:
- The head and uncinate are supplied superiorly by branches of the celiac, which give rise to the GDA (gastroduodenal artery) and superior pancreatic branches
- The head and uncinate are supplied inferiorly from branches of the SMA to the inferior pancreatic vessels
9
Q
most common type of pancreatic cancer?
A
exocrine
adenocarcinoma
10
Q
gastrinoma
A
- The second most common type is the gastrinoma
- Gastrinoma is part of a syndrome called Zollinger-Ellison syndrome (ZES)
- These patients present with high levels of gastrin secretion and have peptic ulcers.
- Ulcers are very common and in gastrinoma, patients can have multiple ulcers (sometimes in unusual locations and very large).
- Surgery is recommended after localization is done with cross-sectional CT imaging
11
Q
medication induced pancreatitis
A
There are direct toxic metabolic defects to the acinar cells directly from a variety of different medications. Classic ones you see on exams will be HIV medications (HAART: highly active anti-retroviral therapy), thiazides for BP patients, and a number of other meds causing this.
12
Q
how does acute pancreatitis present?
A
- What is pancreatitis?
- Pancreatitis is inflammation of the pancreas
- How does it present?
- Typically it presents with abdominal pain that may radiate to the back as well
- Nausea, vomiting, and fever are very classic components of this disease entity
13
Q
SIRS
A
I really want you to focus and think about pancreatitis as a systemic disease, and part of the systemic inflammatory response syndrome (SIRS)
- SIRS can be characterized by:
- Tachycardia (HR >90)
- Tachypnea (RR >20)
- Hypothermia or Hyperthermia (rectal temp <36C or >38C)
- And leukopenic or have leukocytosis (WBC <4k or >12k)
- Really think of it as a systemic disease!
14
Q
insulinoma
A
- The most common type is the insulinoma
- Patients come in with a fasting hypoglycemia
- You treat them with glucose and they feel better
- They also have high insulin levels that can be detected on serology
- These patients can have insulinomas anywhere inside the pancreas, which can be benign or malignant
We usually recommend resection if possible
15
Q
location of the pancreas
A
- The pancreas is posterior to the stomach, abutting the IVC and the aorta
- Again you can see the tail of the pancreas in the hilum of the spleen
- Going from right to left, the pancreas comes across the IVC and the aorta
- As you go out towards the tail of the pancreas, it abuts the splenic hilum
16
Q
treatment of choledocholithiasis (CBD stones)
A
ERCP
17
Q
treatment of acute pancreatitis
A
Treatment of pancreatitis
- If you take away nothing else from this talk, what I want to emphasize is that the treatment is supportive. Most of the time things will get better if you support the patient well.
- Supportive
- NPO: Initially try to rest the GI tract and pancreas.
- The patient becomes NPO (nil per os, meaning to withhold oral food and fluids)
- IVF/electrolyte replacement
- Aggressive fluid resuscitation and replacement of electrolytes as appropriate
- Analgesia
- These patients are in a lot of pain, so you want to control their pain.
- People don’t get addicted meds if you’re giving them pain meds for acute pancreatitis
- You want to aggressively treat their pain and give them electrolytes and fluids as appropriate
- Nutritional support
- In the acute setting and long-term setting, you want to give nutritional support.
18
Q
ERCP
A
- ERCP (endoscopic retrograde cholangiopancreatography): relieves obstruction of bile duct from stones
- This procedure can also lead to pancreatitis sometimes
19
Q
dorsal bud
A
•The dorsal pancreas eventually gives rise to the body and tail of the pancreas, and a small amount of the head.
20
Q
A
Interstitial pancreatitis
- What does interstitial pancreatitis look like radiographically?
- This is a CT scan.
- G = gallbladder
- P = pancreas
- In this picture, the CT scan looks a little bit hazy.
- This is hazy because there is a lot of interstitial edema and stranding around the pancreas
- This is what pancreatitis looks like generally.
- There is a slightly more plump pancreas, with a hazy interstitial inflammation.
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21
Q
annular pancreas
A
Annular pancreas
- Much less common, 1 in 7000 people have a condition called annular pancreas
- “Annulus” means ring
- There is a failed complete rotation and fusion of the two dorsal and ventral buds
- If they don’t fuse properly, they can actually constrict the duodenum
- On the right, this is a figure of a barium study showing that there is a constriction at the duodenum (*)
- Above that proximally, there is dilation of the duodenum
- So, annular pancreas can lead to:
- Duodenal obstruction presenting with nausea and vomiting
- Pancreatitis
- And a lot of other situations
- This disease occurs in 1 in 7,000 people, more commonly in Down syndrome patients
22
Q
venous drainage of body and tail of pancreas?
A
- The body and tail in an analogous way are drained by branches of the splenic vein
- The splenic vein runs from the spleen and joins with the SMV to form the portal vein
- (Essentially this is all you need to know about the venous drainage. There are a lot of vessels around, but if you know these few facts, you already know all you need to know about the arterial supply and venous drainage of the pancreas.)
23
Q
main pancreatic duct
A
- The main pancreatic duct drains through the ampulla of Vater into the duodenum
- The main duct is also called the duct of Wirsung
24
Q
intraductal papillary mucinous neoplasm
A
One variant of mucinous cystadenoma is IPMN (intraductal papillary mucinous neoplasm)
- It is usually within the pancreatic duct (hence, intraductal)
- It can either be in the main duct or in a branch
- It is mucinous, so it secretes the same mucin as in mucinous cystadenoma
- IPMN tends to be more common in men, whereas most cystic lesions then to be more female predominant
- IPMN is interesting because it involves the ductal structures
- If you put an endoscope down, you can see the ampulla Vater (1) and the duodenum (2)
- In this picture, the ampulla of Vater is very wide and it has a “fish-eye” deformity.
- This is the classic finding for IPMN and you can also see a mucinous gelatinous fluid secreting from the Ampulla of Vater into the duodenum
- If you look on CT (B) and MRI (C), you can see a dilated pancreatic duct
25
Q
the endocrine pancreas
A
Endocrine pancreas
- The pancreas is also made of endocrine cells, which are a number of different cells that are within the Islet of Langerhans
- These are polygonal cells that develop sometime around week 9 of embryonic development
- They are separated by a thin capillary network from the bulk of the pancreatic parenchyma
- Recall: the majority of the parenchyma is exocrine
- You can see the Islet of Langerhans in the H&E stain and TEM very nicely
26
Q
minor accessory duct
A
•The minor or accessory duct, which has 10% of the flow, is called the duct of Santorini
29
Q
mucinous cystadenoma
A
- Generally a benign process
- Has a higher pre-malignant potential, and can be anywhere from completely benign to borderline to malignant (which is then called a cystadenocarcinoma)
- These are larger cystic structures, so mucinous cystadenoma is sometimes called macrocystic cystadenoma
- It is filled with mucin, a thick fluid, that is secreted by the lining cells of the cysts.
- This generally shows up in patients in their 50-60s but can be variable
- These have a higher pre-malignant potential. So when they are found we generally recommend surgery if the patient is an appropriate candidate.
30
Q
pancreatic ductal system?
A
We’re going to look at a little bit of embryology
- What’s this yellow structure here (1)? Yes, that’s the pancreas (lol)
- What’s the green structure (2)? Gallbladder
- 3 = Common bile duct
- 4 = Cystic duct
31
Q
vascular supply of the body and the tail of the pancreas?
A
The entire body and tail of the pancreas gets its arterial supply from branches of the splenic artery
33
Q
embryology of the pancreas
A
- In week 4 of embryonic development, there are 2 buds that develop as outpouchings from the endodermal lining. They are called the dorsal bud and the ventral bud, or the dorsal pancreas and ventral pancreas.
- These are essentially outpouchings of the endodermal lining of the early nascent GI tract.
- The dorsal pancreas eventually gives rise to the body and tail of the pancreas, and a small amount of the head.
- Most of the head and the uncinate process come from the ventral pancreas
- The two buds then rotate around what becomes the luminal GI tract, the duodenum.
The buds then fuse sometime in week 7, forming the ductal system
34
Q
Whipple procedure
A
- If pancreatic CA is in HOP and the patient is an appropriate surgical candidate (i.e. not sick from comorbid conditions or metastatic disease that it doesn’t make sense to think about surgery), the definitive surgery is called the Whipple procedure (pancreaticoduodenectomy).
- They resect the distal stomach, the HOP, the gallbladder, biliary tree, and part of the duodenum
- It is a pretty big surgery.
- After this is resected, there are 3 anastomoses made between the biliary tree and the jejunum (called the choledochojejunostomy), between the remnant pancreas (pancreaticojejunostomy), and between the gastric remnant to the jejunum (gastrojejunostomy) (figure 2)
- So, there are 3 anastomoses for the HOP. This is called the Whipple procedure.
36
Q
pancreatic exocrine function
A
- The main functional unit of the exocrine pancreas is the acinus
- The acinus contains proenzymes (inactive enzyme precursors)
- The proenzymes are stored in an inactive state and in response to a variety of signals, these can be released. Their contents flow down the ductal system (into the duct of Wirsung) and into the duodenum where they can cleave proteins, lipids, and so on.
- These are maintained in an inactive state to prevent auto-activation and pancreatitis
37
Q
serous cystadenoma
A
- Almost exclusively a benign process that can affect people in their 50-60s (or sometimes earlier)
- You have these tiny little microcystic structures, which is why serous cystadenoma is sometimes called a microcystic adenoma
- They are lined by cuboidal epithelium
- They secrete a glycogen rich but thin fluid
- These are almost always benign and are generally found incidentally on imaging
- They can cause symptoms though. We often leave them alone, but if they are large or causing symptoms from compression or causing pain, then if the patient is an appropriate surgical candidate, we recommend surgery.
41
Q
pancreas divisum
A
Sometimes these two ducts don’t fuse properly = pancreas divisum
- This happens in 1 out of every 10 people. 10% of people have a condition called pancreas divisum (pancrease divided)
- The two ducts don’t fuse properly
- What happens is that too much of the pancreatic fluid goes through the minor duct (duct of Santorini) and it can predispose to recurrent attacks of acute pancreatitis
- But, its clinically silent in the majority of people who have it – so you may never know you have it
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44
Q
pancreatic pseudocyst
A
- Pseudocyst is a false cyst. It is not epithelial lined. It is NOT a cyst.
- It is essentially a bag of necrotic pancreatic parenchyma, pancreatic enzymes, tissue, and blood
- Note that there is a lot of blood in the H&E stain.
- CT scan
- 1 = liver
- 2 = gallbladder
- 3 = pancreas
- 4 = pseudocyst
- This is much larger than the pancreas and is a pseudocyst
- Why could this be important? There are a number of reasons. What’s right in front of the pancreas? The stomach (5). The pseudocyst is compressing the stomach. Even if the pseudocyst is completely benign and resolved, the patient can’t eat, can’t drink, and probably has nausea and vomiting. Something needs to be done. This is something that can develop in the acute and long term phase.
- Question (can’t hear). Answer: The reason it is a pseudocyst is that it is not epithelial lined. It is essentially dead tissue that gets inflammatory cells around it and over 4-8 weeks becomes walled off. Because it’s not an epithelial lining, it’s not technically a cyst. That is why this is a pseudocyst, a sequelae of pancreatitis.
45
Q
autoimmune pancreatitis
A
steroids work!!
- When they looked at it under the microscope, there were just lymphocytes everywhere.
- So, we are increasingly seeing this as autoimmune pancreatitis, and if you remember what I said about pancreatitis being a systemic disorder, this is the same idea here. This can involve the pancreas, but it can also be associated with other organs and autoimmune disorders like PSC, rheumatoid arthritis, and Sjogren’s syndrome. Some of these patients have salivary gland disease, xeropthalmia, xerostoma, and other manifestations of autoimmune disease.
- If you treat them like an autoimmune disease with steroids, then the patients are cured (for a certain amount of time, since it is a relapsing remitting condition)
- So, we’re very careful with these patients before sending them for resection even though statistically it is more commonly going to be a malignancy. BUT, this still should be at the back of your mind!
48
Q
glucagonoma
A
- Less commonly is glucagonoma
- It can be benign or malignant
- It classically presents with necrotizing migratory erythematous rash
49
Q
anatomic regions of the pancreas
A
Regions of the pancreas (listed from right to left):
- Head of the pancreas
- Uncinate process: small outpouching of the pancreas
- Neck
- Body
- Tail
53
Q
heterotopic pancreas
A
Ectopic or heterotopic pancreas
- Generally a benign condition
- There is heterotopic or abnormal placement of pancreatic tissue à (failure of complete migration of pancreatic tissue during development)
- The pancreatic tissue can appear in various places within the luminal GI tract (i.e. stomach and in this picture, the duodenum)
- It can be clinically silent or be an incidental finding on endoscopy
- It can lead to pancreatitis
- So you can have a patient with pancreatitis of pancreatic tissue in the stomach or the duodenum
•
54
Q
ventral bud
A
•Most of the head and the uncinate process come from the ventral pancreas
