GI Pathology Flashcards
pathologic events
.mucosal breakdown .hemorrhage .obstruction .infection .inflammation .dysmotility .neoplasia
signs/symptoms
.pain .bleeding .emesis .diarrhea .anorexia
Gastroesophageal Reflux Disease (GERD)
a. LES dysfunction
b. Hiatus hernia
c. Peptic esophagitis
d. esophageal complications
> Barrett’s
> Cancer
> Stricture
e. extra-esophageal complications
Esophagitis
Seen in GERD
where acid and pepsin and maybe other enzymes from the stomach are actually acting on unprotected esophageal mucosa and causing enzymatic and chemical reaction that breaks down the lining of the mucosa and we get ulceration or erosion
Lower Esphageal Sphincter Complex (LES dysfunction)
in abnormal closure is abnormality of the relaxation of the lower esophageal sphincter complex, which is made up again up of thickened muscles (that’s the lower esophageal sphincter itself) and these thickening of the diaphragm and some fibers here that are attached. These ligaments here help pull the stomach up and close it.
Hiatal Hernia
there’s been a slippage of these attachment fibers and on the upper part of the stomach that pulls up through the diaphragm.
A hernia is simply a space in the bodies fixation system - whether it’s the abdominal wall or the groin, what have you.
this is a very common cause of reflux because you lose the connection fibers that pull the esophagus close.
Barrett’s Esophagus
Metaplastic tissue formation: the squamous tissue has been replaced by specialized columnar tissue - it’s an intestinalized columnar tissue that has much more goblet cells and is much more typical of what we see in the absorptive cells and secretory cells of the small intestine
Barrett’s esophagus is a precursor to adenocarcinoma
Esophageal Cancer
Two types:
Squamous Cell Carcinoma: from smoking and heavy drinking
Adenocarcinoma: unknown etiology but definitely related to Barrett’s esophagus
Both cancers are equally difficult to manage in terms of long-term survival and both of them produce obstruction – this is the most common presenting symptom. People have trouble swallowing food and then it’s already an invasive lesion and then goes on to metastasize.
Peptic Ulcer Disease
Commonly we can get duodenal ulcers at the jct of the stomach and the small intestine or we can get gastric ulcers.
Peptic Ulcer Disease
Commonly we can get duodenal ulcers at the jct of the stomach and the small intestine or we can get gastric ulcers.
Ulceration in the gastrointestinal lining caused by stress, weight loss, illness, H. pylori infection, NSAIDS (prostaglandin inhibitors)
H. pylori
one of the main players in the physiology of ulcer disease
bacterial infection coming from poor sanitary conditions (passed from hand to mouth)
H. Pylori is now considered so important that it’s a class I or class A carcinogen by the world health organization (WHO). That means it is a proven or thought to be proven producer of cancer
Gastritis Definition
true inflammation of the gastric lining with tracking of WBC/lymphocytes depicting chronic disease.
(acute inflammation is different has lots of granules/neutrophil infiltration)
Gastritis Definition
true inflammation of the gastric lining with tracking of WBC/lymphocytes depicting chronic disease.
(acute inflammation is different has lots of granules/neutrophil infiltration)
another unfortunate form of H.Pylori infection because world wide this is a very common cause of gastric cancer.
Type A v. Type B Gastritis
Type A gastritis: effects proximal part of the stomach (the body); results in loss of the thickness and health of the gastric tissue; common precursor for gastric cancer; loss of ability to make the various hormones that the proximal stomach is responsible for (ex. intrinstic factor for B12 absorption)
Type B: effects The lower part (the antrum); has an atrophy of the antrum, loss of protective mechanisms and that’s where acid related ulcers from H.Pylori occur in the antrum and the duodenum. So type B gastritis is more commonly associated with ulcer disease of the distal stomach and is the more typical ulcers related to H.Pylori Condition.
Gastric Cancer
mostly adenocarcinoma
most common cause we think now in the world is H. Pylori.
2 different common presentations:
- Is in the esophagus where the tumor just penetrate downwards through the different layers.
- second is something called Linitis Plastica, it’s pretty specific to the stomach situation where the cancer starts from the mucosa and buries itself into the submucosa and then spreads along the submucosa. It can almost involve the entire stomach even though it starts at the bottom or the top it just works its way down. So it’ not actually in the inside as it is in between.
Cure rate early is almost 100%
Signet cell is the classic pathologic feature of gastric cancer of adenocarcinoma
Infections in the Small Intestine
typified by diarrhea
It typically doesn’t
produce bleeding or breakdown of the tissue, just a disruption of function.
most common pathogens of the SI diarrhea are either viral or toxin producing bacteria. Parasitic is very common in certain populations in the world (suppressed)
important viruses that we see in the USA are the Adenovirus and the Norwalk agent which is extraordinarily pathogenic, you don’t need many viral particle; also E. Coli and Cholera
Causes villus blunting which decreases absorption
most infectious diarrheas actually are relatively self limited
V. Cholera
adheres to the cell surface and causes the cell to produce a toxin. That causes the villus to secrete. It messed with the potassium, sodium, chloride channel. It opens up a flood gate of fluid from the body’s circulation system – our blood stream supplies lymphatics to the small intestinal submucosa. Those lymphatics communicate with mucosa. If you have a signal that says let water and solute out (as in the signal produced by the cholera toxin) then the blood supply is going to supply the lymphatics, the lymphatics are going to send water through the cell, and you’re going to become dehydrated.
No blunting.
Txt: re hydration
Obstruction Intestinal Problems
a. clinical features
- pressure that is the result of a compression or compaction – as you’re pressing more and more down against the obstructed area, you get an increase in pressure; consequence is PAIN! press hard against the wall of your intestine, the wall of the intestine would get thin and it would get so thin that basically the blood wouldn’t’t be able to get through the blood vessels. So you’re actually pressing on the BV of the wall of the intestine when you increase the pressure; this leads to ISCHEMIA –> GANGRENE –> DEATH
b. causes
- internal hernia
- tumors
- eat something that got stuck
- built up scar tissue
c. sequelae
- treatment for obstruction is not to fix the blockage. It’s to get rid of all the fluids. Put a tube down and suck all the juices out.
Crohn’s Disease
a. pathology
- disorders of the WBC function in our body. We used to think they were a reaction to an infection, “immune disease”. They’re a disorder of the way cytokines act on natural killer cells, T cells, helper cells, B cells, suppressor cells, and the environment
b. extent of disease
- Chrohn’s disease can affect anywhere from the mouth to the anus.
c. clinical features
- cobble stoning
- patchy
- very fibrotic; fibrosing or fibrostenotic, which means fibrosis causes stenosis
- transmural
- can involve the sinus tracts called fistulae
- Classical finding surgically is this creeping fat sign
- Histopathologically, you get these non-caseating granulomas.
- If you do a biopsy or an endoscopy – Crohn’s and Ulcerative Colitis are almost impossible to tell apart even though they are very different
- Both cause stricturing, diarrhea, bleeding, etc. and they are both predisposing factors to cancer
• Extra-intestinal features will go away if you cure the Ulcerative Colotis or Crohn’s disease – it is linked through the immune mediation but we don’t
know exactly how
Celiac
Clinical Features: you absorb or mal-absorb a number of different things especially fat. And if you malabsorb fat, you malabsorb fat associated vitamins: A, D, E, and K. As a result, you can become hyper-coaguable
Also, because you’re malabsorbing vitamin D, you become calcium deficient and osteoporosis is a common sequella of substantial celiac disease and it’s one of the few causes in men for osteoporosis
a common and important cause of anemia in people who aren’t bleeding
Pathology: This is a lymphocytic infiltration. Allergy to gluten. It’s an important cause of nutritional deficiencies and diarrhea in an important sub-segment of the population – 2%. Treatment is avoidance of gluten bc it’s simply an allergy to gluten. It’s like an internal rash!
the lymphocytes cause villi to go from up there to down there in terms of there appearance
Familial Adenomatous Polyposis (FAP) syndrome.
heterozygous but of variable penetrance
have a virtual 100% chance of getting the cancer because they go on to develop hundreds of colon polyps, and start developing colon polyps in their teens
treated by colon resection because otherwise it’s an unpresentable cancer presenation.
hereditary nonpolyposis colon cancer syndrome (HNPCC)
a defined mutation that leads to dozens of colon polyps in patients who have inherited that gene, and extraordinary high risk of colon cancer but not 100% colon cancer rate
Lynch syndrome
a well defined genetic mutation but lynch is not just a colon cancer disease but also uterus, breast, bladder, and ovary. So lynch patients have mutation, and have a higher risk of having bunch of other diseases….and again, something that is defined, testable…and they don’t have polyposis like FAP or HNPCC, but they much more likely to develop colon cancer or bad polyps then the average person
Gallstone Disease
if there is an inadequate
mixture of bile and lecithin, crystallization will be favored and stones can form
RISK FACTORS:
- certain people that don’t contract their gall bladder well – so there is not proper stirring of the bile
- Supersaturated bile – can be genetic
- High estrogen states
> overweight
> female
> pregnant
-Low metabolic states like when you are not eating enough the gall bladder slows down
TYPES OF GALLSTONES:
(1) Cholesterol gallstones –most of the ones we see in the US
(2) Bilirubin/Black gallstones
Bacterial Infections of the Large Intestine
Antibiotic-related (C. difficile)
> Iatrogenic
> C. difficile is so common in healthcare because we come
into contact with patients
Pathologic feature: globs of pseudomembranes – pus globs that adhere to the mucosal surface (macro/microscopic); Pseudomembranous colitis
–> abscesses
Of the colon, the most important infection is traveler’s diarrhea –contract something through food and end up with a bacterial disease that causes inflammation of the colon – colon would look diseases – red, infiltration of neutrophils, edema, widening of lamina propria
With time it heals itself – there is little post-inflammatory
disease, it is usually self-limiting
E. coli, campylobacter, Yersinia, etc.
Parasitic Infections of the Large Intestine
More important worldwide than in the US
Chronic inflammation of the bowel that infiltrates into the colon
wall
This produces a pathologic finding under the microscope (unlike
diseases of the small intestine)
Ulcerative colitis
Pathology;
> Abnormality of the normal T cell function –
abnormal cytokine release, cell function, the way
antigens are processed
> Autoimmune mediated disease
> Idiopathic unexplained dysregulation of the immune
function
Regional variations
> Only affects the colon from the anus to the cecum
>Only affects the inner lining of the mucosa
>Acute disease with crypt abscess
Extra-intestinal manifestations
>Unusual rashes of the skin
> Inflammation of the joints
Prmary sclerosing cholangitis (70% of primary scleroising cholangitis occurs in patients with either ulcerative colitisor Crohn’s disease)
CAN BE CURED BY CUTTING IT OUT – unlike Crohn’s
Neoplasms/Polyps
• Pathophysiology
o Over time, multiple mutational hits from adenoma to cancer
o Adenocarcinoma is the glandular cancer
o Poorly preserved foods with toxins can cause it
o Western diet high in meats and fats and lower in vegetables – this predisposes people as well
• Natural history
o Colon has a thick wall which is a barrier to malignancy
o Chance of dying of colon cancer is less than some other kinds of cancer
o Rate of colon cancer is going down because in almost all people you need a precursor adenoma lesion in order to form colon cancer
• Polyp syndromes
o Familial adenomatous polyposis (FAP)
o NHPCC
o Lynch Syndrome
Colon Cancer
• Epidemiology & Risk factors
o #1 risk factor is cigarette smoking, #2 is obesity
o Other risk factor is genetics – certain genetic features have a dramatic increase in the rates of colon cancer
• Staging
o TNM model
- T-IS: limited to mucosal layer (IS – in situ)
• T1: can go through mucosa into submucosa – can
spread to lymph nodes)
• T2: gone into muscle wall
• T3: through muscle wall, able to go to other organs
• T4: spread to adjacent organs
• Overall staging (combination of TNM stages):
Stage 1: limited disease
Stage 2: large tumor, no lymph nodes
Stage 3: lymph node disease
Stage 4: metastatic
Screening decreases the INCIDENCE of colon cancer because it catches people before their polyps have become colon cancer; Good at preventing colon cancer because you can get rid of polyps before they progress; no other disease (maybe besides skin cancer) where SCREENING PREVENTS DEATH
Start colon cancer screening around age 50
Diverticolosis vs. Diverticulitis
Diverticolosis is a common disease where pockets form off the colon
Diverticulitis is an infection and inflammation of one
of those pockets that occur from pressure, causing
an outpouching along a natural weakness in the
colon wall
Don’t know what causes a person with diverticulosis to get an infection of what of these pockets leading to diverticulitis
Appendicitis
A form of bowel obstruction
Appendix is a hollow tube – probably has a role in helping with immune
surveillance
As it sits there with time, in 10-15% of the population, some kind of a stool ball gets stuck and hardens, blocking off the appendix, so if there is an
obstruction, the appendix gets more and more filled and the fluid cannot get out
This causes the dilation of the lumen, leading to pressure (pain), which causes thinning of the wall, which causes ischemia, which over time
causes gangrene and then perforation
Appendolith or fecolith is the main cause of appendicitis
Almost all people with appendicitis need to have surgery to remove it – the stone likely will never dislodge itself
Cholecystitis
classic disorder of Gallstone Disease: gallstones are getting stuck and producing obstruction. (thinning of the wall, ischemia of the wall, and then perforation) causing PAIN!!
So Chronic Cholecystitis would be a thickening of the mucosa with evidence of chronic inflammatory cells (that is-lymphocytic infiltration), even some scar tissue, which is a result of repeated episodes of inflammation
Acute Cholecystitis where you have a neutrophil infiltration and an acute inflammation
Obstructive Jaundice
Common bile duct stones – stone moves and goes to
obstruct the main tube system – this causes an obstruction to the passage of bile, so the bilirubin cant even get out of the blood into the liver, and you get a backup of bilirubin in the skin and the eyes and there is no way to excrete this –this is jaundice
Obstructive jaundice is an obstruction at the bottom of the bile duct
Biliary pancreatitis
If there is a stone that goes and obstructs pancreas flow,
this can cause activation of the cascade that we call
pancreatitis
Enzymes that are normally present in the pancreas but not normally activated are abnormally activated due to the gall stone
Cholangitis
Chol = bile duct; angitis = infection
CAUSES SEPSIS**
As the stone gets down to the bottom, it can allow for the ingress of bacteria from the duodenum
Passage of non-sterile contents into the bile duct – would not normally be a problem since there would be fluid passage to wash it out, but if there is a blockage due to a stone the bacteria get stuck and can pass up into the smaller sections of the bile ducts and canaliculi
These small sections of the bile duct are in thin layers of cells – bacteria can get into the blood stream and causes sepsis.
Gallbladder Carcinoma
• Adenocarcinoma of the innermost lining layer of the gallbladder (3 layers: inner mucosa, submucosa containing lymphatics and blood supply, and an
outer muscle layer)
- Not a very common cancer but when it does develop it is almost universally fatal since it has a thin wall and does not have any kind of protective layer around it and just floats in the peritoneal.
- Risk factors are:1) having gallstones (constant irritation)
2) cigarette smoking
Cholangiocarcinoma
- Bile duct cancer that can happen anywhere along the ductal system of the liver and extrahepatic system (main bile duct)
- When it is within the confines of the liver it is called a cholangiocarcinoma
• Klatskin Tumor: complicated cancer near the confluence (Y shaped area) of the bile duct system
o Very difficult tumor to treat because it is difficult to
operate here and can affect the lower segment
and the upper two segments of the bile duct
Primary Sclerosing
Cholangitis
- Inflammatory disease of the bile duct system
- Idiopathic – don’t have an exact etiology for it, although we know it is associated with certain other inflammatory conditions
• PATHOLOGIC FEATURE: onion skin pattern
o Relatively normal bile duct mucosal lining, but just
outside of that you have an onion skin pattern of
radiating wings of fibrous tissue– little cells with
fibroblasts
o These produce stricturing
o Immune/idiopathic inflammatory condition with
stricturing
- Infection of the bile duct causing this appearance would not be primary –the primary cause of this would be the infection
- If you had an operation and there was scarring around the bile duct – this would also be secondary
- Primary is where you have no causes that can be identified and you still have areas of stricturing
- You can get areas of “beading” that you might see on an x-ray
Acute Pancreatitis
• Etiologies – initial injury triggers inflammation (50/50 alcohol/gallstones)
o Alcohol (most common cause in those who drinks)
o Gallstones (most common cause in those who don’t
drink)
o Toxins (Scorpion bites, some medications)
o Autoimmunity
• Histologically: influx of acute inflammatory cells, necrosis of health tissue, influx of edema/fluid causing swelling
• Pathophysiology
o Influx of various cytokines trigger a systemic and local response to injury – influx of white blood cells, alteration of blood flow and lymphatics cause increase in fluid and a swelling of the pancreas
• Clinical sequelae
o Fever, generally feeling ill – all related to the
inflammatory response
• Inflammatory response
o Necrosis
o Hemorrhage
o Fluid collections
Chronic Pancreatitis
• Caused by mini-episodes of acute pancreatitis, but it does not have the process of severe inflammation with fluid and swelling and sepsis-like symptoms
o Many mini-episodes with a little inflammation with pain that get better and then more and more episodes; the getting better part is what causes chronic pancreatitis
o Repeated disruption and destruction of cells and loss of normal tissue; laying down of more collagen
• Histologically, you would see a lot fewer acini, atrophic ducts with no juice flowing, a lot of inflammatory cells like lymphocytes, and
laying down of collagen/scar tissue
• Clinical features: stone formation
• Etiologies
o Alcohol (most common cause)
o Congenital abnormalities
o Cystic fibrosis and other gene defects
- Gene defects affect ability of trypsin to stay in
its “safety” mode so it activates much more
easily, leading to bouts of inflammation
throughout life
o Autoimmunity
o NOT gall stones – gall stones are only
associated with acute pancreatitis
• Clinical sequelae
o Different than acute (in acute you either live or
die)
o Here you have lost both exocrine and endocrine
function so you become diabetic and you lose the
ability digest food so you don’t absorb nutrients
you need
o People lose weight and have nutritional deficiency
o Chronic pain
Pancreatic Cancer
• Epidemiology:
o 4th leading cause of cancer deaths in the US
o Frequency has continued to increase
• Risk factors:
(1) Cigarette smoking
(2) Genetics – family history of pancreatic cancer = 3x
incidence, more than 1 person in the family = 7x
incidence
(3) Obesity
(4) Adenocarcinoma that is pushed along by the
effects of having excess fat in the body, either
because it stores hormones or because it triggers
inflammation
• Clinical presentation
o Body or tail = weight loss or abdominal pain
o Head = the tumor forms over the bile duct, so it
gets obstructed causing jaundice (this is another
form of obstructive jaundice) without pain
o Presentation in the head is usually earlier than in
the body or tail
• Prognosis/Treatment
o There are drugs that work but the cure rate is less
than 10%
Achalasia
- Esophageal motor disorder
- Loss of esophageal peristalsis and failure of the lower esophageal sphincter to relax in response to swallowing
• Dysphagia to solids and liquids, regurgitation
and retrosternal pain
Gardner Syndrome
- Intestinal polyps
- Extraintestinal lesions:
- Osteomas
- Epidemoid cysts
- Odontomas
- Impacted teeth/supernumerary
- Fibromas
- Lipomas
Tuberous Sclerosis (TS)
Inherited GI polyposis syndrome; part of FAP
Enamel pitting (97%)
Oral fibromas (69%) in the gingiva
Facial angiofibromas
Comorbidities – epilepsy - renal disease and pulmonary disease
Peutz-Jeghers Syndrome
Inherited GI polyposis syndrome; part of FAP
Mucocutaneous melanin pigmentations and a unique type of GI polyp (can be found in stomach and orally)
Cowden Syndrome
Inherited GI polyposis syndrome; part of FAP
- Multiple hamartoma syndrome
- Facial trichilemmomas
- Keratoses
- Palpilomatous papules (gingival and buccal mucosa) Cobblestone appearancce
- Mucosal lesions- lipomas, neuromas/hemangiomas
- Fissured tongue
- Macrocephaly
- Mental retardation
- Epilepsy
- Vitiligo
- Xanthomas
