Exam 1 Flashcards
(279 cards)
1
Q
Type of epithelium in GI tract
A
- Proximal and distal ends = stratified squamous non-keratinized
- Remainder = simple columnar
2
Q
Histologic layers of GI tube
A
- Mucosa (epithelium, lamina propria and muscularis mucosae). LP contains glands. MM is 2 smooth muscle layers.
- Submucosa: vascular, lymphatics, nerve plexuses in some regions. In esophagus and duodenum, there are glands here.
- Muscularis externa: inner circular, outer longitudinal.
- Serosa (mesothelium is outer most limiting layer of this and it is simple squamous epithelium). Esophagus has adventitia, which is just outer layer of CT, not epithelium.
3
Q
Location of nerve plexuses within the GI tract? Function?
A
- Meissner’s (aka submucosal): consists of PSNS and SNS post-G fibers – activity of muscularis mucosae (SM), secretory activity of glands, blood flow
- Auerbach’s (aka myenteric): between inner and outer longitudinal muscle layers. Consists of PSNS and SNS post-G fibers – regulates activity of muscularis externa (SM).
4
Q
What is Z-line of esophagus?
A
- Cross over from stratified squamous non-k epithelium to simple columnar epithelium. This the GE (gastro-esophageal) junction. LES is just above this line.
5
Q
What is Barrett’s esophagus? What is necessary for histologic diagnosis? What is the risk of having this?
A
- Metaplasia: stratified squamous epithelium of esophagus becomes simple columnar epithelium with goblet cells (KEY for diagnosis). Use Alcian blue stain to stain acidic mucous from goblet cells.
- Occurs in response to constant assault by stomach acid during reflux for example.
- Risk of adenocarcinoma
6
Q
What two cancers can develop in the esophagus? What parts?
A
- Distal 1/3rd for adenocarcinoma
- Middle 1/3rd for squamous cell carcinoma – may be due to constriction site??
7
Q
What type of esophageal cancer would most likely cause hoarseness?
A
- Squamous cell carcinoma more likely in middle 1/3rd. Proximity to left recurrent laryngeal nerve (off vagus).
8
Q
4 esophageal constrictions. Clinical relevance?
A
- UES (at cricopharyngeus muscle)
- Aortic arch
- L primary (main) bronchus
- Diaphragm (T10)
- Mnemonic: I ate ten eggs at noon
- IVC (through caval): T8
- Esophagus (through esophageal hiatus): T10
- Aorta (through aortic hiatus): T12
- Note: 2 and 3 combined clinically, considered one point of constriction
- Clinical relevance: endoscopy and pill esophagitis at these regions
9
Q
What is Zenker’s diverticulum? How can it form? Symptoms?
A
- Cricopharyngeus (UES level) and thyropharyngeus muscles constitute the inferior pharyngeal constrictor muscle with thyropharyngeus being superior portion and crycopharyngeus being inferior portion.
- Transition (Killian’s triangle) area between fiber orientation bw these two muscles = point of weakness where a Zenker’s (aka pharyngoesophageal) diverticulum can form (usually left-sided).
- Symptoms: halitosis (food gets stuck there)
10
Q
Areas that can form diverticula in esophagus? What is most common?
A
- Pharyngoesophageal (Zenker’s) = most common
- Mid-esophageal
- Epiphrenic
11
Q
What vessel would you ligate when performing a thyroidectomy in order to maintain arterial supply to the esophagus?
A
- One of subclavian branches = thyrocervical trunk. Branch off this = inferior thyroid artery. Branch off this = esophageal branch which supplies the cervical region of esophagus.
- Ligate distal to the branch
12
Q
What happens in the esophagus during portal HTN?
A
- Esophageal varices formation. Risk of rupture.
13
Q
What is achalasia? Sign to look for on imaging?
A
- Loss of inhibitory neurons (and secretions of NO and VIP) in the myenteric plexus. Normally these fire with bolus of food is present = relaxation. Result of loss = contraction.
- Imaging: Crow’s beak
14
Q
Describe lymphatic arrangement in esophagus and clinical relevance of this.
A
- Lymph flows readily in submucosal lymphatic channels which is arranged longitudinally. This facilitates spread of cancer distally or proximally to nidus.
- Superior to tracheal bifurcation: lymph flow is usually upwards and therefore cancer spreads toward neck (IJ, paratracheal nodes, subcarina, paraesophageal nodes)
- Inferior to bifurcation: lymph flow downward, cancer spreads towards celiac and cardiac nodes
15
Q
What lymphatic structures must a surgeon pay attention to during esophageal surgery? Why?
A
- Thoracic duct is posterior tot eh esophagus. This is the main lymphatic emptying duct for the body (entire left-side and upper left neck and left limb). Destruction = chylothorax = lymphatic fluid in pleural space
16
Q
Why could the antrum of the stomach be removed in cases of refractory peptic ulcer disease?
A
- The antrum contains a large population of G cells (brown staining), which secrete gastrin. Parietal cells under gastrin influence secrete HCl.
17
Q
Where do most ulcers form in the stomach?
A
- Lesser curvature proximate to the angular notch.
18
Q
What is ZE syndrome? Where are these typically found? How are they diagnosed?
A
- Tumor of gastrin-producing cells.
- Gastrinomas (stain brown d/t G cells w/ prominent rugae d/t increased parietal mass) are typically found in the gastrinoma triangle: confluence of common hepatic and cystic ducts, junction of third and second parts of duodenum and junction bw neck and body of pancreas.
19
Q
Describe blood supply to stomach. Clinical relevance of this? Which arteries need to be severed after fundoplication? Should surgery necessitate, can the left gastric artery be ligated?
A
- ) left gastric artery (off celiac trunk): proximal portion of lesser curvature
- ) short gastric arteries from splenic a (off celiac trunk): to stomach closest (fundus) to spleen
- ) left gastro-omental (gastroepiploic) artery (off splenic): left side of greater curvature
- ) right gastro-omental (gastroepiploic) artery (off gastroduodenal): right side of greater curvature
- ) gastroduodenal (from common hepatic artery)
- ) right gastric artery (off hepatic artery proper): right lesser curvature
* don’t need to know exact locations for this exam, this is just review
- Clinical relevance: stomach blood supply preserved even after ligation of several.
- Fundoplication: sever the short gastric arteries
- Ligation of left gastric artery: variation = left hepatic artery comes off left gastric artery instead of from hepatic artery proper. Must determine if this variation exists in the patient.
20
Q
Can a denervation surgery be performed to treat refractory peptic ulcer disease? If so, what are the considerations?
A
- Selective vagotomy to nerves from the anterior branches off the left/anterior vagus trunk to remove innervation to parietal cells. Must not sever the anterior nerve of Latarjet supplying the pylorus and pyloric sphincter.
- Also the criminal nerve of Grassi (branch off the right/posterior vagus trunk) must be severed as they also innervate parietal cells
21
Q
A patient with gastric cancer also presents with obstruction of pancreatic ducts. Why?
A
- Anatomic relationship to pancreas and mass effect
- More common = cancer metastasis through lymphatic channels that run along the right gastro-omental vessels to pyloric lymph nodes embedded in the head of the pancreas
22
Q
Three structural modifications that serve to increase surface area in SI
A
- Plicae circulares: folds of submucosa and mucosa
- Intestinal villi: process off muscosa
- Microvilli
23
Q
Describe 4 signature changes to surface area histology in celiac sprue (gluten enteropathy)
A
- Enterocytes disarrayed
- Villi atrophy
- Crypt hyperplasia
- Inflammation of LP
24
Q
What happens to plicae circularis during a case of enteritis?
A
- Thickened
25
Parts of the duodenum
- 4 parts
- Superior (bulb/ampulla) – intraperitoneal
- Descending: entry of common bile / pancreatic duct unification forming hepatopancreatic ampulla (of Vater)
- Horizontal/inferior: bw aorta and SMA
- Ascending
26
Where do most duodenal ulcers occur? Why is this location of concern?
- Ampulla/bulb – this is the 1st part (superior, proximal 2/5th).
- This is intraperitoneal, therefore ulcerous erosion can take place into gastroduodenal artery and pancreas. Liver and GB can be affected too.
27
What is a radiologic sign of an anterior duodenal ulcer in the superior part?
- Air accumulation below diaphragm
28
Landmark used to diagnose incomplete rotation or malrotation of the small intestine?
- Ligament of Treitz, which attaches the duodenojejunal flexure to the diaphragm.
- It serves as landmark between upper and lower GI bleeds
29
What is the landmark used to divide between upper and lower GI bleeds?
- Ligament of Treitz, which attaches the duodenojejunal flexure to the diaphragm.
30
At what level does the SMA come off?
- ~ L1
31
Wrt organization of celiac trunk and SMA, what is the clinical relevance when it comes to an embolic occlusion entering into the vessels?
- It is more likely to enter the SMA as it makes an acute angle with the aorta. The celiac trunk makes a 90 degree angle off aorta.
32
What is SMA syndrome?
- Compression of duodenum by the SMA may result in weight loss due to the loss of fat at angle bw SMA and aorta, lumbar lordosis and lower origin of SMA
33
What is intussusception? What is the most frequent segment? Which group does it occur more in?
- Bowel segment telescopes into adjacent segment. Blood flow to telescoped region is compromised and may lead to necrosis.
- 95% of these occur in children. In adult, 90% of time due to pathologic process with cancer being leading cause.
- Most frequent segment = ileocolic
34
What is the position of the appendix?
- McBurney’s point: 1/3rd distance from ASIS to the umbilicus
35
Describe possible mechanisms of appendicitis
1. Luminal obstruction by fecalith or lymphoid hyperplasia = intraluminal pressure increase = ischemia of wall and invasion of bacteria
2. Bacterial or viral infection = ulceration from infection/inflammation
36
What are diverticula? Two types?
- Outpouchings of the bowel wall. Occur at weak points within wall.
- True: involve all layers
- False/pseudo: only mucosa and submucosa
37
Where are diverticula more likely to occur in bowel? Most common site?
- Between tenia coli where only circular muscle exists and at sites further weakened by blood vessels penetration (typically on the mesentery side)
- Most common site = sigmoid colon. Rectum is spared.
38
Where is the most common site for a duodenal diverticulum?
- 2nd part of the duodenum where pancreatic, bile ducts enter (weakest area).
39
What is IBD? Describe two types. Which can lead to fistulae formation?
- IBD: inflammatory bowel disease. GI tube is in constant antigenic challenge mode. When out of control, inflammation rules leading to UC or Crohn’s.
- UC usually only involves submucosa and mucosa of large intestine (sometimes terminal ileum)
- Crohn’s involves any segment (mouth to anus) w/extraintestinal complications possible. Fissures can occur, penetrating through wall and into other lumenous structures such as other bowel, urinary bladder or cutaneous.
40
Where is colon cancer more likely to lead to an obstruction?
- Right-sided colon is larger than left, therefore obstruction more likely on left side where diameter smaller.
- Also, material more solid in left colon and not able to move past obstruction well, whereas in right colon, more fluid in nature (not yet dehydrated).
41
If patient had colon cancer resulting in bleeding, which side would you expect the cancer if you saw bright red blood? Occult blood?
- Left side for bright red blood
| - Right side for occult blood
42
Which segment of the large intestine is the most vulnerable to ischemia and why?
- Splenic flexure. This is where middle colic artery of SMA and left colic of IMA anastomose and an area called the critical point of Griffiths. The terminal branches of these anastomoses are thin and the marginal artery is of small caliber.
43
What is the arc of Riolan and what is its clinical relevance?
- Present in ~ 10% of the population, it is connection between SMA and IMA typically the middle colic and the left colic.
- If surgery necessitates ligation of IMA make sure to ligate proximal entry of this vessel.
44
During a cholecystectomy, a particular anatomical landmark(s) must be identified. What is/are the landmark(s)?
- Triangle of Calot (aka hepatocystic triangle) bordered by:
a. Cystic artery (sometimes moved to the liver margin)
b. Cystic duct
c. Common hepatic duct
45
What does the ectoderm give rise to in the GI system?
- Stomodeum (primitive mouth)
- Proctodeum (anal pit)
* gives rise to the epithelium associated with these areas
46
What does the endoderm give rise to in the GI system?
- Most of the epithelium lining the GI tube except for most proximal and distal. Also the digestive glands
47
What does the mesoderm give rise to in the GI system?
- Mesoderm (splanchnic mesenchyme) gives rise to muscular walls and CT of GI tube
48
Divisions of the primitive gut and structures associated with each part? What artery supplies each division?
1. Foregut: pharynx to duodenum (distal to opening of bile duct, 2nd part)
- pharynx, respiratory system, esophagus, stomach, duodenum (distal to opening of bile duct), liver, pancreas, biliary apparatus
- artery: celiac trunk
2. Midgut: duodenum distal to right half (2/3rd) of transverse colon
- distal duodenum, jejunum, ileum, cecum, vermiform appendix, ascending colon, right half (2/3rd) of transverse colon
- artery: SMA
3. Hindgut: distal transverse colon to superior part anal canal
- left 1/3rd of transverse colon, descending colon, sigmoid colon, rectum, superior portion of anal canal, epithelium of urinary bladder and most of epithelium of urethra
49
Describe development of the esophagus
- Both derived from foregut
- Single tube divides into laryngotracheal tube and esophagus separated by tracheoesophageal septum
- The septum separates
- Esophagus is short initially and then elongates normally. Recanalization occurs. Caudal brachial arches provides striated muscle in upper esophagus. Splanchnic mesenchyme (mesoderm) provides the smooth muscle in remaining esophagus.
50
Explain how esophageal atresia and stenosis occurs. In what location is esophageal stenosis most frequently found?
- Esophageal atresia results from deviation of tracheoesophageal septum or failure of recanalization (d/t apoptotic events)
- Esophageal stenosis (most frequently in mid to distal) results from:
a. Sequestered respiratory tissue elements found in esophagus (hyaline cartilage, respiratory epithelium)
b. Fibromuscular hypertrophy d/t myenteric plexus damage
c. Mucosal diaphragm (incomplete bridge between mucosa)
51
Explain how tracheoesophageal fistula can occur. What is the most common pattern?
- Incomplete separation of lung bud from foregut
| - Most common pattern = atretic proximal esophagus with distal esophagus forming fistula with trachea
52
What is a short esophagus?
- Esophageal tube is short initially in development and elongates. Failure of elongation results in short esophagus, which pulls part of the stomach into the thoracic cavity resulting in lung hypoplasia (no space for lungs to grow).
53
What is a Lusorian artery?
- Anomaly off of aorta.
- Normally branching of aorta is BCS. With this anomaly, right CC branches off first then CS. Note: no R subclavian. Following CS, the lusorian artery (aberrant R subclavian comes off)
- Result: aberrant artery wraps posterior to esophagus to the right resulting in constriction of esophagus (difficulty swallowing food)
54
Describe development of the stomach wrt directional expansion, greater and lesser curvatures, direction of rotation, which sides face ventrally and dorsally and vagus nerve placement on either surface
- Dorsal growth dilatation rate exceeds ventral growth rate and dorsal surface becomes greater curvature, ventral surface becomes lesser curvature. Original left = ventral, original right = dorsal.
- 90 degree rotation occurs so that left vagus is on anterior surface of stomach and right vagus is on posterior surface. Mnemonic = LARP – left ant, right post
- Also, clockwise movement about AP axis results in duodenum on right and stomach on left of body
55
What is infantile hypertrophic pyloric stenosis? What is hallmark sign of this in infant?
- Marked thickening of pylorus d/t pyloric muscle hypertrophy. US shows up as donut
- Result = passageway restricted and projectile vomiting (hallmark sign) occurs. Tx with myotomy.
56
Describe development of duodenum.
- Develops from caudal part of foregut and cranial part of midgut with junction being just distal to the common bile duct
- C-shaped loop forms as foregut and midgut grow resulting in duodenum. As stomach rotates, duodenal loop rotates to the right. Open C faces left, closed C faces right.
57
Blood supply to the duodenum
- Foregut portion: celiac trunk
| - Midgut portion: SMA
58
Causes of duodenal stenosis and atresia. What are the 3 types of atresia?
- Stenosis causes: incomplete recanalization, annular pancreas (collar around 2nd part of duodenum)
- Atresia causes: recanalization doesn’t occur. 3 types = mucosal diaphragm, fibrous cord, absence of connection between proximal and distal parts.
- In either case, Sonic hedgehog signaling implicated
59
What is the double bubble sign?
- Result of duodenal stenosis. Proximal part is dilated and smaller bubble. Distal stomach is larger bubble.
60
Differentiate duodenal atresia/stenosis causes from that of jejunal or ileal atresia/stenosis causes.
- Most frequent cause of jejunal or ileal atresia/stenosis is a vascular accident as opposed to failure of / incomplete recanalization.
61
What is the presentation of vomitus in duodenal atresia vs stenosis?
- Stenosis, vomitus usually contains bile
| - Atresia, vomitus almost always contains bile
62
Describe development of livery and biliary apparatus wrt structures formed from cranial portion and caudal portion of hepatic bud
- This system forms from caudal part of foregut. Liver bud forms 2 parts as it grows:
a. Large cranial part forms liver
b. Small caudal part forms gallbladder and cystic duct
63
What is Alagille syndrome?
- Most common cause of familial intrahepatic cholestasis
| - Mutations in notch pathway leads to decreased number of bile ducts in portal spaces
64
Describe development of midgut. What do the cranial and caudal limbs of the foregut form?
- 3 stages: herniation, reduction, fixation
a. Herniation:
- Cranial and caudal limbs of midgut are positioned around SMA on an AP axis
- Cranial limb herniates into umbilical cord and rapidly elongates. Caudal limb elongates more slowly. These undergo 90 degree counterclockwise rotation.
b. Reduction:
- Reduction of herniation occurs with another 90 degree counterclockwise rotation (to 180 total thusfar). Caudal limb now superior.
c. Fixation:
- Another 90 degree counterclockwise rotation occurs.
- Cranial limb returns first with reduction to left side (right side is occupied by liver). This limb forms the small intestines. Caudal limb forms the large intestine and is positioned right starting with the appendix and cecum. This forms the large intestine.
65
What is an omphalocele? How did this occur?
- Omphalocele is failure of reduction during midgut development. Result = bowel present outside the abdomen through the umbilicus.
66
What is an umbilical hernia? How did this occur?
- Reduction of midgut occurred during development, but a defect in closure of anterior abdominal wall is present allowing for re-herniation.
67
Describe rotational defects of the midgut. What is the result in terms of organ placement?
1. Non-rotation (misnomer): first 90 degrees of rotation occurred during midgut development. Left side now contains caudal limb (large intestine) and right side contains cranial limb (small intestine). Usually asymptomatic.
2. Reversed rotation: midgut loop rotates 270 clockwise instead of counterclockwise. Result = SMA compresses the transverse colon resulting in possible stenosis. Here the duodenum is anterior to the SMA and TC is posterior to SMA.
3. Mixed rotation / volvulus: see another flashcard
68
What is a volvulus and mixed rotation? What signs are seen radiographically?
- Mixed rotation = cranial limb moves 90 degrees counterclockwise as it should, but caudal limb stays in position inferiorly. Next 180 degrees occurs with cranial limb, again caudal limb remains in position.
- Result: Cecum lies inferior to pylorus. Peritoneal bands forms pivot points around which small and large intestine can twist forming volvulus. This can lead to duodenal obstruction and also blockage of arterial supply resulting in necrosis of involved segments.
- Radiograph: corkscrew and whirl-pool signs (see L3 slide 20)
69
What is Meckel’s diverticulum?
- Aka ileal diverticulum. Common malformation of digestive tract.
- This is a true outpouching of all layers of the ileal wall.
- Sometimes it contains gastric mucosa with parietal cells and can form ulcer. Other times it can be attached to anterior abdominal wall via fistula or just a fibrous cord.
70
What is annular pancreas?
- Ventral bud of pancreas should be a single lobe. If bilobed, they can wrap around 2nd part of duodenum causing duodenal stenosis (double-bubble sign seen).
71
What is pancreas divisum?
- Abnormality in formation of pancreatic ducts. Main outflow from pancreas is through narrower minor sphincter into duodenum instead of through papilla of Vater (major). Result = increase in ductal pressure = chronic pancreatitis.
72
Describe derivation of anal canal. Describe the blood supply, lymph drainage and innervation to the anal canal.
a. Proximal upper 2/3rd from hindgut: epithelium here from endoderm
- Blood: superior rectal artery and vein
- Lymph: inferior mesenteric LNs
- Innervation: ANS, non-painful if lesion/cancer here
b. Distal 1/3rd from proctodeum: epithelium here from ectoderm
- Blood: inferior rectal artery and vein
- Lymph: superficial inguinal LNs
- Innervation: somatic via inferior rectal nerve, painful if lesion/cancer here
73
Define pectinate line and white line of Hilton
- pectinate line = division between proximal and distal anal canal derive from hindgut and proctodeum respectively – line = junction of epithelium change
- white line = aka intersphincteric line separating internal and external sphincter, epithelium above = keratinized and below is non-keratinized. This is stratified squamous.
74
What is Hirschprung’s disease?
- aka congenital megacolon
- Failure of ENS plexuses (primarily myenteric) to develop in the rectum d/t failure of crest cell migration. Result = narrowing of rectum (+/- sigmoid involvement) with dilation proximal.
75
Sucrose composition
- Glucose and fructose
76
Lactose composition
- galactose and glucose
77
Maltose composition
- 2 x glucose
78
What bonds does alpha-amylase hydrolyze?
- Alpha-1,4-glycosidic bonds in start and glycogen
79
Phases of CHO digestion
1. Oral phase: action of alpha-amylase
2. Intestinal phase: isomaltase and alpha glucosidase complete breakdown into mono, di and trisaccharides. Disaccharidases breakdown disaccharides into glucose, galactose and fructose.
80
Can humans degrade beta-1,4-glycosidic linkages?
- Not, only alpha-1,4 (in amylose, amylopectin and glycogen). Cannot digest cellulose with its beta-1,4
81
Isomaltase function
- Alpha-limit dextrin with alpha-1,6-linkages requires isomaltase to degrade it into glucoses/maltose
- Also generates glucose and fructose from sucrose
82
Describe glucose uptake from intestinal lumen all the way to the cells
- Glucose is taken up into enterocytes via SGLT-1 (co-transporter with Na), a secondary active transporter (ATP-dependent indirectly)
- Glucose exits on basolateral aspect via facilitated diffusion through GLUT-2 down concentration gradient into the circulation
- Glucose is moved from circulation into cells down concentration gradient via facilitated diffusion (various GLUT transporters)
83
Describe fructose uptake from intestinal lumen all the way to the cells
- Fructose is taken up into enterocytes via GLUT5 via facilitated diffusion.
- Fructose exits on basolateral aspect via facilitated diffusion through the GLUT-2 transports.
84
How does lactose intolerance cause diarrhea? How is lactose intolerance diagnosed?
- Lactose broken down by bacteria. Carbon metabolites draw water into the intestine.
- Diagnosis: hydrogen breath test – H2 made by bacteria, diffuses into circulation and removed by lungs
85
Pepsin. Where is it secreted? Function?
- Stomach
| - Breaks down large proteins into small fragments
86
Function of CCK
- stimulate intestinal mucosal cell to secrete enteropeptidase (cleaves trypsinogen to trypsin)
- stimulates pancreatic secretion of trypsinogen
87
Digestive enzymes released from the pancreas that degrade proteins
- Chymotrypsinogen, trypsinogen, procarboxypeptidases, proelastase
88
Enzymes produced by intestinal epithelium that degrade proteins
- aminopeptidase, dipeptidase and endopeptidase
89
What enzymes prevents premature activation of trypsinogen in the pancreas? What does deficiency of this lead to?
- Trypsin inhibitor. Result of deficiency = autodigestion of pancreas leading to pancreatitis
90
Function of trypsin
- Cleaves other pancreatic zymogens to active state. Also acts on trypsinogen to make more of itself.
91
How does CF affect the pancreas? Clinical relevance.
- Deficiency in CFTR leads to thickening of pancreatic mucus = impaired secretion of pancreatic enzymes.
1. 10% of CF patients develop pancreatitis secondary to blockage of pancreatic duct
2. Weight loss d/t malabsorption
92
What is cystinuria?
- Ineffecient reuptake of cystin (Cys-Cys) in the kidney. Cystin crystals form in GU tract d/t low water solubility
93
What is Hartnup disease?
- Defective uptake in neutral amino acids from intestine and kidney filtrate. Results in shortage of tryptophan for NAD-synthesis causing Pellagra-like symptoms.
94
Function of pancreatic lipase
- Separates 2 FAs from TAG
95
Apoprotein associated with chylomicron from enterocyte
- ApoB48
96
How common is lactose intolerance?
- Up to 90% of the population
97
Occurrence of celiac disease
- 1/250 Caucasians
98
Compare immune responses via mucosal antibody vs that of serum antibody
- Mucosal antibody response is months to a year. Serum antibody response persists for decades.
99
What is primary, secondary and tertiary lymphoid tissue?
- Primary: tissue where generation of mature, but antigen naïve T and B cells occur. Bone marrow and thymus.
- Secondary: tissue where naïve lymphocytes reside while waiting to be activated. Lymph nodes, tonsils, Peyer’s patches, spleen.
- Tertiary: where the elimination of antigen occurs. Technically anywhere where infection can occur – skin, GI, lungs, vagina etc
100
What is GALT?
- Gut associated lymphoid tissue – Peyer’s patches (in lamina propria), appendix, lymphoid aggregates in large intestine/lamina propria throughout GI
101
In what layer of the GI tube are Peyer’s patches found?
- Mucosa, specifically in the lamina propria
102
What antibody is produced in mucosal sites?
- IgA
103
What are M cells? Why else are these important?
- These are cells with specialized folded membranes found at the ‘dome’ of Peyer’s patches. These endocytose/phagocytose antigens from the gut lumen and transfer them to APCs in lymphoid tissue underlying them.
- Portal of entry for Salmonella, Yersinia, Listeria, Shigella
104
What cell types are found at immune mucosal sites?
- M cells: at dome of PP – endocytose/phago antigens from gut lumen
- IELs (intraepithelial lymphocytes): alpha-beta CD8+ - cell-mediated immunity
- Lamina propria: mainly CD4 T cells, B lymphocytes, plasma cells, macrophages, DCs, eos, mast
- Mast: elicit food-induced allergic reactions (normal response in plasma = IgE-mediated parasitic defense)
105
Describe an immune response in the GI tract.
- M cells transport antiens
- APCs stimulate TH cells
- TH cells stimulate antigen-specific B cells, GCs form
- Pre-plasma cells leave PP through efferent lymphatic channels, enter bloodstream through thoracic duct and home back to lamina propria (addressins)
- Pre-plasma cells become plasma cells, secret IgA
- IgA binds to poly-Ig receptors of epithelial cell. They are transported across cell and delivered to mucosal surface. Here they bind microbes, prevent access to epithelium and promote clearance.
106
Function of poly-Ig receptors on epithelial cell in gut. What is secretory component? Function?
- Binds IgA on basolateral side and transports it to mucosal/apical side.
- Secretory component = piece of poly-Ig receptor that protects IgA from being degraded in lumen of gut (extends half-life)
107
Classes of IgA
- Mucosal (dimeric) and serum IgA (monomeric)
- subclasses = IgA1 and A2
o IgA1 is cleaved by bacterial IgA1 protease. IgA2 is not susceptible to this. IgA1 can fix complement via alternate cascade, while IgA2 cannot.
108
Function of IgA
- opsonizes small pathogens for phagocytosis
- causes eos degranulation via FcAlphaR for anti-parasite immunity
- Ultimately prevents binding of microbes to epithelia and facilitates expulsion
109
Function of gamma-delta T cells
- Normal/typical T cells are alpha-beta
- These gamma-delta are significant in GI tract
- Role: ?Serve as antigen-nonspecific initial line of host defense?, respond to non-peptide molecules of some microbes, don’t recognize MHC-associated peptides, but can recognize non-peptides on class I-like CD1, may respond to small number of microbial antigens until conventional adaptive immune response can take place, antigens responded to: HSP, nts, phospholipids
110
What is oral tolerance? Why do we care?
- Tolerance: immune system says don’t respond to certain antigens (eg. self).
- Oral tolerance: don’t respond to foods/commensal bacteria that we want as nutrition/defense. This aids to prevent hypersensitivity to ingested food proteins.
- High dose of oral antigen leads to clonal deletion of lymphocytes specific to antigen. Low dose leads to clonal anergy and reg T cells suppress immune responses including systemically. This may have utility for tx of autoimmune diseases (MS, RA, T1 DM, uveitis)
111
What is selective IgA deficiency?
- Most common immunodeficiency in humans. Absence of IgA. Most individuals go through entire life not knowing they have this issue.
- Associated with higher risk for autoimmune dz.
112
Food hypersensitivities tend to be mediated by what antibodies?
- IgE
113
Describe immunopathology seen in gluten-sensitivity enteropathy
- B and T cell infiltrates can be seen in affected sites / lesions of intestine
- Alpha-beta CD4 and 8 cells are increased
- IELs bearing gamma delta are up by 10-15 x
- Anti-gliadin IgA may play a role, but main damage appears to be T cell-mediated
114
Compare and contrast the immunologic basis of inflammatory bowel disease (between UC and CD)
- UC: begins as diffuse lymphocyte-rich infiltrate leads to granulocyte (neutrophils) inflammatory cells during abscess formation
- CD: begins as lymphocytic infiltration leads to classic macrophage-containing granulomatous lesions
115
Clostridium botulinum.
a. Organism info and pathogenesis
b. Symptoms/signs of GIT infections
c. Epidemiology
d. Tx
a. G pos rods, spore-forming (ends of cells) – resistant to boiling
- A-B exotoxin. A enters nerve cell, B attaches to receptors on motor nerve ending = block release of ACh. Actual bacteria doesn’t do much in adults.
b. Botulism:
- 12-36 hours after ingestion. Sx = dizziness, dry mouth, blurred or double vision (eye weakness), abdominal pain, NVD or C (disruption of ANS) present in as few as 30% of cases, progressive paralysis (resp failure = most common cause of death). No fever!
- Floppy baby syndrome (intestinal botulism): infants less than 6 months where commensal organisms not yet fully inhabited. Mild form characterized by constipation followed by generalized paralysis.
c. Foodborne, improperly canned foods, soil
d. Tx = IV antitoxin (horse derived) – watch for serum sickness. Enema, gastric washing, surgical removal of dirt/dead tissue. May require artificial respiration.
116
Clostridium difficile.
a. Organism info and pathogenesis
b. Symptoms/signs of GIT infections
c. Epidemiology
d. Tx
a. G pos rod, spore-forming
- Clindamycin first abx to cause. 2nd and 3rd generation cephalosporins are most common causes now. Chemo also cause.
b. Pseudomembranous colitis:
- C.diff with white-yellow plaques on colonic mucosa, non-bloody neutrophilic stool in half cases, fever and abdominal cramping, toxic megacolon can occur. Toxin present in stool. Culture not telling as present in a small number of population who are asymptomatic.
c. Most common cause of nosocomial diarrhea, fecal-oral transmission
d. Tx = withdraw abx, oral metronidazole (preferred) or vanc
117
Shigella dysenteriae.
a. Organism info and pathogenesis
b. Symptoms/signs of GIT infections
c. Epidemiology
d. Tx
a. Gram neg rods, non-lactose fermenting (colorless on MacConkey), distinguished from Salmonella by (no gas from glucose ferm, no production of H2s, non-motile).
- Highly virulent (only 100 needed), invades mucosa (distal ileum and colon) = bloody diarrhea, rarely invasive into bloodstream.
b. Dystentery (enterocolitis)
- 1-4 days incubation, fever, cramps, watery diarrhea initially later bloody mucous
c. Severe disease from S. dysenteriae. S. sonnei milder dz. Travel, poor sanitation.
d. Tx: mild dz = fluid/electrolyte therapy. Severe: fluoroquinolone (cipro) = drug of choice. Peds: TMP-SMX or azithromycin. Black box warning: tendinitis, tendon rupture.
118
How to distinguish between salmonella, e. coli and shigella?
- Salmonella and shigella are non-lactose fermenters (colorless MacConkey)
- E. coli is a lactose fermenter (purple on MacConkey)
- Shigella is non-motile, does not produce h2s, no gas produced from glucose fermentation
- Salmonella is motile, produces h2s and gas from glucose fermentation
119
Salmonella.
a. Organism info, pathogenesis (3 forms)
b. symptoms/signs of GIT infections, other (3 forms)
c. Epidemiology
d. Tx
a. gram neg rods, non-lactose fermenting, h2s producing w/flagellar H and vi capsular component
- enterocolitis (typhimurium): invasion of epithelium and subepithelium = inflammation and diarrhea, limited infection d/t neutrophils
- enteric fever (typhoid fever by typhi): begins in SI with few symptoms, multiply on M cells of Peyer’s patches, spread to phagocytes of liver, GB and spleen = bacteremia. LPS induces fever and other symptoms. Carrier state.
- Septicemia: from enterocolitis, rare
b.
- Enterocolitis: 12-48 hr incubation, NV, abdominal pain, diarrhea (+/- blood)
- Typhoid fever: flu-like, fever +/- constipation, bactermic load high = fever, delirium, tender abdomen and enlarged spleen, rose spots (on abdomen, rare), LFTs abnormal
- Septicemia with metastatic infections: osteomyelitis
c. not discussed, poor sanitation, contaminated food
d. Tx:
- enterocolitis: self-limited usually, fluid/electrolyte. Abx in mild cases can increase chance for carrier state, so don’t give.
- enteric fever, septicemia and only severe enterocolitis: ceftriaxone or cipro. Chronic carriers of typhi, use amp or cipro. Carrier state tx may need to include cholecystectomy
120
E. coli
a. Organism info, pathogenesis of the 4 types
b. symptoms/signs of GIT infections, other (4 forms)
c. Epidemiology
d. Tx
a. Gram neg rod, lactose fermenter (MacConkey purple), H and K antigens – many different strains
- ETEC: adhesins adhere to intestinal mucosa, release of toxins similar to cholera, SI
- EIEC: similar to shigella, invades mucosal cells = destruction, LI
- EPEC: plasmid dependant adhesins = loss of microvilli, actin fibril platform, SI
- EHEC/STEC: toxins similar to shigella, no penetration into epithelium
b.
- Traveler’s diarrhea (d/t ETEC: T for Travelers): NV, abdominal cramps, massive watery diarrhea, dehydration, no blood
- EIEC gastroenteritis: fever, cramps, blood/pus in feces
- EPEC gastro: fever, V, mucous watery diarrhea
- EHEC gastro: bloody diarrhea, HUS (lysis of RBCs and kidney failure)
c. Epidemiology:
- ETEC: sanitary; EPEC: outbreaks in hospital nurseries, bottle fed infants in developing countries (chronic diarrhea in infants) rare in US; EHEC: food outbreaks
d. Tx: fluid replacement, infants (gent, polymyxin), fluoroquinolone for ETEC, ETEC prevented with bismuth preparations
121
Vibrio cholera.
a. Organism info, pathogenesis
b. symptoms/signs of GIT infections
c. Epidemiology
d. Tx
a. Gram neg curved rod, tolerates strong alkaline/salt concentration
- cholera toxin: heat labile, B binds cell, A = activation of AC = cAMP production = fluid out
b. severe rice water diarrhea, vomiting onset, NO PMNS in stool!
c. -
d. Tx = electrolytes and fluid replacement
122
Campylobacter jejuni.
a. Organism info, pathogenesis
b. symptoms/signs of GIT infections
c. Epidemiology
d. Tx
a. Gram neg curved rod, motile, microaerophilic!
- ?
b. fever, vomiting, diarrhea, abdominal cramps, dysentery (bloody diarrhea) in half cases
c. –
d. Tx: most cases don’t require abx, if severe tx with erythromycin or cipro
123
Helicobacter pylori.
a. Organism info, pathogenesis
b. symptoms/signs of GIT infections
c. Epidemiology
d. Tx
a. Gram neg spiral, microaerophilic (like C. jejuni) with multiple sheathed polar flagella
- burrows into mucosa, urease to create alkaline environment
b. Gastritis: urease pos
c. Cluster in families, FO route, well water, flies capable of transmitting, low SES
d. Tx: PPI + clarithromycin + amoxicillin or metronidazole (if pen allergy)
124
What is achalasia? Symptoms? Causes? Complications?
- Failure of relaxation of LES
- Sx: progressive dysphagia, nocturnal regurg, young adults, functional obstruction
- Causes: usually idiopathic, failure of distal inhibitory neurons containing NO & VIP, degenerative changes innervation (decreased myenteric ganglia). Secondary: Chagas dz (T. cruzi destroys ganglia), disorders of DVMN (surgery, polio), diabetic neuropathy, infiltrative disorders (sarcoidosis, cancer etc.)
- Complications: SCC, aspiration, esophagitis, diverticula, obstruction, candida esophagitis
125
What is hiatal hernia? Symptoms? Causes? Complications?
- Part of stomach extends above diaphragm
- Sx: only ~ 10% symptomatic, heartburn, reflex, regurg w/ incompetent LES
- Cause: unknown, separation of diaphragmatic crura with widening
- Complications: sliding hernia (~95%), paraesophageal (~ 5%) – can become strangulated
126
Is Zenker diverticulum true or false?
- UES false
127
What is Mallory-Weiss syndrome? What populations are at risk? Causes
- Longitudinal tears at GE junction d/t failure of reflex relaxation of LES. Hiatal hernia predisposes one to this.
- Risk: pregnancy, alcoholism
128
What is the major cause of upper GI bleeding?
- Peptic ulcer disease
129
Main cause(s) of esophageal varices?
- Alcoholic cirrhosis (develops in 90% of these patients, causes ½ deaths – many times these are asymptomatic)
- 2nd most common cause worldwide = schistosomiasis
130
What is esophagitis? Symptoms? Cause (incl most common)?
- Inflammation of esophageal mucosa
- Sx: dysphagia, heartburn, regurg, hematemesis, melena (iron digested in upper GI)
- Causes: REFLUX, Barrett’s, infections/chemical esophagitis, eosinophilic
131
Causes of reflux esophagitis
- Anything that decreases efficacy of anti-reflux mechanisms of LES: CNS depressants, pregnancy, obesity, irritants (etoh, smoking, hot fluids, chemo, infection (herpes), radiation, GVHD, autoimmune etc.), scleroderma, hypothyroidism, delayed gastric emptying
- Also sliding hiatal hernia, delayed clearance of gastric content (increased gastric volume)
- Increases in intra-abdominal pressure
132
Describe morphology of reflux esophagitis
- Eosinophils (early marker)!, neutrophils, lymphocytes
- Basal zone hyperplasia
- Elongation of lamina propria papillae
- Superficial necrosis, ulceration
133
What condition(s) predispose one to Barrett’s esophagus?
- Reflux esophagitis. 10% of symptomatic esophagitis patients develop this
134
What is Barrett’s esophagus? Criteria for diagnosis? Complication of this?
- distal squamous mucosa = metaplastic columnar epithelium w/goblet cells (key)
- Complication: 30-40 x risk increase for adenocarcinoma (most in Barrett’s)
135
Etiology of esophageal strictures
- Peptic, caustic, inflammatory, ischemic, post-op, radiation, congenital, infectious, traumatic, scleroderma
136
What can happen to the esophagus as a result of scleroderma?
- Stenosis leading to strictures.
| - Overwhelming fibrosis is seen in these patients
137
Most common benign tumor of esophagus
- Overall these are rare – Leiomyoma (smooth muscle tumor)
138
What malignant tumors can occur in esophagus?
- Epithelial origin cancers: squamous cell carcinomas (most common) and adenocarcinomas (glandular)
- Note: usually discovered late, therefore survival not good. Also location leads to spread / extension.
139
What is the most common cancer of esophagus worldwide?
- Squamous cell carcinoma (about ½ of esophageal cancers in US and 90% worldwide). Highest in Iran, northern China, SA, southern Brazil accounts as hight as 20% of all cancer deaths.
140
Risk factors for squamous cell carcinoma of esophagus
- Dietary (nitroso compounds) and environmental factors strongly implicated
- chronic esophagitis, etoh, heavy smoking, achalasia, carcinogens in food (= chronic inflammation = high cell turnover = dysplasia = CA), dietary deficiencies, HPV
- Males > females (4:10), AA 4 x Caucasians
141
Squamous cell carcinoma of esophagus metastasizes where first?
- Mediastinal
142
Clinical features of squamous cell carcinoma of esophagus
- Progressive gradual dysphagia – lumen occluded 30-50% before recognized
- Steady substernal or back pain
- EXTREME WEIGHT LOSS and debilitation
- Hoarseness, cough, hemorrhage and sepsis
- This is similar to adenocarcinoma
143
Morphologic types of esophageal SCC
- Protruded (~60%): polypoid, fungating
- Flat: diffuse, infiltrative
- Excavated: necrotic, ulcerates deeply into surrounding structures
144
In what location do most squamous cell carcinomas of esophagus occur?
- Middle 1/3rd
145
Where do most adenocarcinomas arise in esophagus?
- Distal 1/3rd
146
Risk factors for adenocarcinoma
- Barrett’s, tobacco, obesity
| - M >> F, Caucasians > B. Different to SCC: AA > Caucasians
147
Describe molecular findings of adenocarcinoma of esophagus
- Mutation of overexpression of p53 often implicated
148
Describe micrograph findings of adenocarcinoma of esophagus
- Mucin-producing, signet-rings
149
Symptoms of adenocarcinoma of esophagus
- Similar to SCC (progressive dysphagia, substernal / back pain that is steady, extreme weight loss/debilitation, hoarseness, cough, sepsis, hemorrhage)
- Long-term symptoms of heartburn, regurg, epigastric pain d/t reflux
150
BMP components
- Na, K, Cl, HCO3, BUN, creatinine, glucose, Ca
151
CMP components
- BMP + AST, ALT, T bili, Alk phos, T protein, albumin
152
LFTs
- ALT, AST, alk phos, PT, INR, albumin and bili
153
Are LFTs measures of liver function only?
- No. AST also can come from muscle. Alk phos can come from bone
154
AST. Source?
- Liver, skeletal muscle. Released when cells are damaged
| - Also brain, RBCs and heart
155
ALT. Source?
- Liver primarily. Also kidney, skeletal and cardiac muscle.
156
AST:ALT ratio
- 2:1
| - mnemonic: scotch and tonic
157
Do elevations in AST and ALT always indicate alcoholic liver dz?
- No. Consider evaluating for rhabdomyolysis
158
What lab values are up in cholestatic injury pattern?
- alk phos
| - bili (total, direct)
159
When is direct bili rubin increased? Indirect?
- Direct: biliary drainage in adequate
| - Indirect: liver failing to process as quickly as red cells are lysing
160
Alk phos. Source? When is it elevated?
- Source: liver, bone, placenta. Also kidney and intestines
| - Elevated in stretch/inflammation of biliary tree. Also in bone dz including: met prostatic cancer, paget dz. Also CHF.
161
How to determine if alk phos is from liver?
- gamma glutamyl transferase (not included on CMP)
162
Lab values used to determine liver synthetic function?
- Bili, albumin, INR
163
What should be suspected if patient has a total protein minus albumin of > 3.5?
- Autoimmune dz or cancer
164
What markers are likely elevated if patient with cirrhosis presents in a coma?
- Ammonia (source from bacteria). Usually converted to urea in liver. In severe liver dz or portal HTN, concentration of ammonia rises = hepatic encephalopathy
- This is significant predictor of mortality
165
What is primary biliary cirrhosis? What markers are elevated in this dz?
- Destruction of intra hepatic bile ducts typically in MIDDLE AGED FEMALES. Also associated with Sjogrens and Raynauds
- Alk phos (disproportionate increase) + antimitochondrial antibody
166
What is primary sclerosing cholangitis? What markers are elevated in this dz?
- Destruction of intra and extra hepatic bile ducts. More common in MALES. Associated with UC!
- Disproportionate increase in alk phos, imaging shows beads on a string bile ducts, biopsy = onion skinning of bile ducts
167
What is autoimmune hepatitis? What markers are elevated in this dz?
- Liver inflammation (HEPATOCELLULAR DAMAGE) that is autoimmune. Most often in young FEMALES.
- ANA, anti-smooth muscle antibody. Also anti liver-kidney-muscle ab, elevated total IgG levels
168
You suspect iron overload, check what lab?
- iron studies including ferritin
169
You suspect copper overload, check what lab?
- ceruloplasmin
170
You suspect celiac disease, check what labs?
- tissue transglutaminase, antigliadin, IgA levels
171
You suspect hepatocellular cancer, check what labs?
- alpha fetoprotein
172
Defined acute vs chronic. How are they differentiated in terms of morphology
- Acute: mucosal inflammatory process, does not extend past the muscularis mucosae
o Cells: neutrophils
- Chronic: long term mucosal inflammatory changes leading to mucosal atrophy and intestinal metaplasia (goblet cells now seen). Can progress to dysplasia
o Progression: early = red mucosa with infiltration to more severe = atrophy, thin flat mucosa, metaplasia to late = atrophy, dysplasia, CIS
o Cells: lymphocytes/plasma cells
173
Pathogenesis of acute gastritis
- Multifactorial.
- Disruption of mucous layer
- Stimulation of acid secretion
- Decrease of bicarb buffer
- Decrease in mucosal blood flow
- Direct damage to barrier itself
- Neutrophilic inflammation
174
Causes of acute gastritis
- NSAID use (ASA), etoh, smoking
- Chemo, gastric radiation
- Uremia (kidney dz)
- Systemic infections
- Severe stress, trauma (mechanical too), burns
- Ischemia and shock
- Suicide attempts
- Reflux of bilious material
175
Clinical presentation of acute gastritis
- Hematemesis, melena, fatal blood loss occasionally
176
Clinical presentation of chronic gastritis
- Most asymptomatic. Otherwise same as acute: hematemesis, melena, fatal blood loss
177
Causes of chronic gastritis
- Chronic H. pylori infection
- Pernicious anemia
- Etoh, smoking
- Bile reflux, mechanical, radiation
- Crohn’s disease
178
What is the most common GI infection in the world?
- H. pylori
179
What are risks of having H. pylori infection?
- Increase risk for PUD, 5x increased risk for CA, 2-4$ develop gastric lymphoma
180
Does pernicious anemia have an increased risk for carcinoma? Lymphoma? How does this compare to H.pylori infection?
- Increased risk for carcinoma, not for PUD and lymphoma. Also increased risk for endocrine tumors.
- H. pylori = increased risk for PUD, carcinoma and lymphoma
181
Pathogenesis of H. pylori infection
- gram neg s-shaped rod, flagellated
- swims through mucus
- urease buffers gastric acid allow it to liver at proper pH
- binds to epithelial cells via adhesins on its surface
- some strains produce CagA and VacA
o CagA = IL8 induction to attrack neutrophils
o VacA = destruction of epithelium through vacuolization
182
Diseases associated with H.pylori?
- MALT lymphoma, gastric ulcer, duodenula ulcer, gastric cancer, gastric atrophy, acute/chronic gastritis
183
Is achlorhydia seen in H. pylori induced chronic gastritis?
- No. This is seen in autoimmune-induced (such as pernicious anemia) where parietal cells have been destroyed and are unable to produce acid.
184
What are peptic ulcers? How does this compare with gastritis? Most common locations?
- Breach in mucosa anywhere in GI tract extending through muscularis mucosa into submucosa or deeper.
- Most common = stomach, duodenum. 98% located in 1st portion of duodenum or stomach (4:1)
185
Which patients is PUD most commonly seen in?
- alcoholic cirrhosis, COPD, chronic renal failure, hyperparathyroidism (high CA = increased gastrin production)
186
Clinical presentation of PUD
- Gnawing epigastric pain (may mimic cardiac pain) relieved by food or alkalis occurring 1-3 hours post-food, worse at night.
- N, V, bloating, belching, weight loss
- Melena, hematemesis
- Perforation (sepsis, death) = complication, often times first indication
187
Which peptic ulcers always require biopsy?
- Those in stomach. Per Carnevale, don’t biopsy ulcer in duodenum as it is never cancerous
188
Pathogenesis of PUD
- Imbalance between mucosal defense and damaging forces (gastric acid, pepsin) combined with injury from environment and immunological agents
- Impaired defense = ischemia, shock, delayed emptying, reflux
189
Do all patients with PUD have hyperacidity
- Not all. Must have gastric acid and pepsin however.
190
Causes of PUD
- H. pylori – present in almost all duodenual ulcers and most gastric ulcers
- Chronic NSAID use
- Smoking, etoh, corticosteroids, stress, COPD, renal failure, hyperparathyroidism
- Gastrinoma (ZES)
191
Describe morphology of benign gastric ulcer vs malignant
- Benign: raised edges, non-irregular or distorted, punched out appearance
- Malignant: high raised edges that are raggedy, distorted shape, not cookie-cutter
192
Describe four demonstrable zones histologically of ulcer
1. Necrosis of ulcer base and margins
2. Zone of non-specific inflammatory infiltrate, usually neutrophilic
3. Active granulation tissue in deeper levels
4. Solid fibrous or collagenous scar (fibrosis)
193
What are major causes of death in those with PUD? What are other complications?
- ¼ of deaths = bleeding
- 2/3rd of deaths = perforation leading to peritonitis, sepsis and death
- Other complications = obstruction, intractable pain
194
Most common acute stress ulcers are located where? Causes?
- Stomach, duodenum and esophagus. Multiple circular lesions. No breaching of muscularis mucosa
- Shock, sepsis, surgery, extensive burns, severe trauma (Curling ulcers), CNS conditions that lead to increased ICP (Cushing ulcers)
195
What are gastric polyps? Types?
- Mass lesions arising and projecting above mucosa
- Types:
a. Hyperplastic or inflammatory (~ 90% of them): non-neoplastic, seen often in chronic gastritis
b. Adenomatous (gastric adenomas): neoplastic, malignant potential
c. Other: fundic gland, hamartomatous, juvenile
196
What is the main malignancy of the stomach?
- Primary gastric carcinoma (90-95%)
| - Others = MALTomas, GISTs, carcinoid, metastatic carcinoma
197
What is the 2nd most common cancer in the world?
- Gastric carcinoma
198
Two types of gastric carcinoma. Describe each. Incidence between males and females
1. Intestinal type: colonic adenocarcinoma. These are gland-forming.
- male more predominant
2. Diffuse type: signet-ring cells (nucleus pushed to side by mucin present in cells). Linitis plastic is example of this. Starts growing within wall causes a thickened wall consisting of malignancy with signet-rings.
- no male predominance
* note: most prevalent in Asia
199
What increases one’s risk for gastric carcinoma?
- Environmental: H. pylori (most important factor in intestinal type – increases risk 5-6 x). Lower SES
- Diet: nitrites, smoked/salted foods, pickled, chili, lack of fresh fruit/veg
- Host factors: chronic gastritis, gastrectomy partial, adenomas, Barrett’s
200
Where are gastric carcinomas more likely to be located in stomach?
- lesser curvature mid to lower portion
201
What is most important prognostic indicator when diagnosing gastric carcinoma?
- Depth of invasion
202
Where do gastric carcinomas metastasize to? What type are they usually?
- Virchow node: supraclavicular node
- Sister Mary Joseph nodule: periubmilical area. Usually intestinal-type.
- Krukenberg tumors: ovaries. Usually diffuse-type.
203
What are GISTs?
- Gastrointestinal stromal tumors. Account of 1-3% of gastric malignancies
- Composed of mesenchymal cells of Cajal. Majority c-KIT positive.
- Respond to TKIs
204
Review pictures from Carnevale’s Pathology of Stomach L9
Review pictures from Carnevale’s Pathology of Stomach L9
205
What is idiopathic IBD? Etiology?
- Chronic relapsing inflammatory disorders of intestinal tract. Refers to Crohn’s (CD) and ulcerative colitis (UC).
- Etiology: idiopathic, probably results from unregulated and exaggerated immune responses to normal gut flora. T-cells are culprits
- CD: probably chronic delayed-type hypersensitivity rxn as sometimes granulomas are seen
- UC: excessive stimulation of TH2 causative, no consistent pattern
206
How to diagnose IBD?
- No single test. Use clinical history, x-rays, lab tests and histology.
- ANCA: anti-nuclear cytoplasmic antibody. 75% positive in UC, 11% in CD.
- Anti-saccharomyces cerevisiae (ASCA): specific and sensitive for CD
207
What is Crohn’s disease?
- Chronic ulceroconstrive inflammatory bowel dz characterized by:
a. Anywhere in GI tract, most common ileum
b. Transmural involvement with mucosal damage
c. Presence of non-caseating granulomas
d. Fissuring with fistulae can occur
208
Clinical presentation/course of CD
- Variable, intermittent bouts o diarrhea, fever, pain, stress precips, weight loss, progressive fluid loss, weakness, anemia
- Strictures, obstruction, fistulas
- Steatorrhea, pernicious anemia
- Extraintestinal manifestations: migratory polyarthritis, sacroiliitis, ankylosing spondylitis, erythema nodosum (red skin plaques), clubbing fingertips, primary sclerosing cholangitis, mild hepatic pericholangitis, uveitis
209
Is there a risk for carcinoma in CD and UC patients?
- Yes, CA risk in CD less than in UC
210
Morphological findings in CD. Include micrograph findings
- Skip lesions, linear apthoid ulcers, cobblestone mucosa, rubber hose thick wall, luminal narrowing (string sign), creeping fat, fissures, fistulae, abscess
- Micrograph: neutrophil infiltrate, metaplasia, mucosa atrophy, architectural distortion, ulceration, transmural inflammation w/lymphoid aggregates, non caseating granulomas (epithelioid macrophages, sometimes giant cell)
211
What is ulcerative cholitis?
- Ulceroinflammatory disease limited to colon and only affecting mucosa and submucosa typically
212
Morphological findings in UC? Histologic findings?
- Rectum involved, colon only (may have backwash colitis) – predominantly left-sided, no skip lesions, lesions continuous, no granulomas, pseudopolyps
- Histology: neutrophil infiltration in LP, crypt abscesses and distortion, atrophy of mucosa, architectural distortion, ulcerations, no granulomas, submucosal fibrosis, pseudopolyp or flat dysplasia. Involvement only in mucosa and submucosa. Thinning of bowel or normal.
213
Clinical presentation/findings of UC
- Remitting, relapsing lower abdominal pain and cramps, relieved by defecation which is bloody and mucoid diarrhea, fever, weight loss, stress = precipitant
- Extraintestinal manifestations can occur: arthritis, liver dz, skin lesions
214
Are polyps seen in Crohn’s disease?
- No, typically in UC
215
Complications of UC
- Toxic megacolon, perforation, CARCINOMA
216
Are fistulae seen in UC?
- Not typically as involvement is only with mucosa and submucosa. Unlike CD, which involves all layers.
217
Where does ischemic colitis most often occur?
- Watershed areas such as splenic flexure (SMA and IMA area of blood supply) and rectosigmoid (IMA and hypograstric area of blood supply)
218
Causes of ischemic bowel dz
- Multifactorial
- Arterial embolism, thrombosis (arterial/venous), low-flow states (CHF, afib, hemorrhage, shock, vasoconstrictive drugs), radiation injury, volvulus, stricture, herniation
219
Types of bowel infarction. Describe clinical and histologic findings in each?
1. Transmural: acute vascular obstruction, medical emergency (100% mortality without treatment)
- Clinical: acute abdomen – bent over in extreme pain + guarding
- Histology: all layers involved, fibrinopurulent exudate, gangrenous bowel
2. Mural and mucosal infarction: acute or chronic hypoperfusion.
- Clinical: non-specific abdominal complaints, bloody diarrhea (sometimes not), obstruction presentation = acute abdomen (if d/t stricture from chronic ischemia)
- Histology: involves entire mucosa and extends into submucosa = luminal hemorrhage, segmental and patchy, no serosal involvement, can lead to ulceration, fibrosis and stricture
220
What is angiodysplasia? Clinical finginds? Histologic findings?
- Non-neoplastic vascular dilation and malformation of submucosal and mucosal blood vessels in cecum and ascending colon. Can be part of systemic disorder.
- Clinical: bloody diarrhea (not melena) – acutely or chronic
- Histologic: mucosa and submucosa contains interconnected vascular network that are dilated.
221
Causes of bloody diarrhea
- Angiodysplasia, diverticulosis and severe hemorrhage
222
Review Slides from L10-12 Pathology of Small and Large Intestines
Review Slides from L10-12 Pathology of Small and Large Intestines
223
What is diverticular disease? Describe histologic morphology of these? Symptoms?
- Refers to focal weakness in colonic wall coupled with increased luminal pressure. Weakest area where small mesenteric vessels penetrate the muscularis propria.
- If multiple outpouchings, this refers to diverticulosis. If inflammation in addition = diverticulitis.
- Morphology: false diverticula, only involve the mucosa and submucosa, not muscularis propria
- Symptoms: only 20% symptomatic. Cramping, lower abdominal pain/discomfort, constipation, sense of not being able to empty rectum.
224
Where are most diverticula found?
- Sigmoid colon (~ 95%)
225
Causes of diverticula
- Low fiber diet, Western diet, exaggerated peristaltic contractions, decreased stool bulk
226
Complications of diverticular disease
- Diverticulitis = most common.
| - perforation, abscess, peritonitis, fistulae, hemorrhage
227
Intestinal obstructions most often occur where?
- Small bowel
228
Symptoms of intestinal obstruction
- Pain, distention, vomiting, constipation, failure to pass gas
229
Causes of intestinal obstruction
- Hernias, adhesions, intussusception, volvulus account for > 80% of cases. 10-15 % of cases d/t tumors or infarction
230
Most typical hernias
- External: inguinal, femoral, umbilical
| - Less common = internal hernias d/t adhesions
231
Complications of hernias
- Incarceration, strangulation
232
Compare and contrast: inguinal hernias (direct vs indirect)
- Defined in comparison to inferior epigastric artery
- Indirect inguinal: lateral to artery, through inguinal canal next to spermatic cord into scrotum. Congenital or acquired.
- Direct inguinal: medial to artery, through Hasselbach’s triangle contained by external oblique m or pushes through superifical inguinal ring, not in spermatic cord. Acquired, never congenital.
233
What are adhesions? Causes? Complications?
- Fibrous bridges bw bowel segments or abdominal wall.
- Causes: peritonitis, surgery, infection, endometriosis, rarely congenital
- Complications: internal herniation, obstruction, infarction
234
What is intussusception?
- Telescoping of bowel segments into one another by wave of peristalsis = trapping of invaginated segment pulled with mesentery (+ vessels)
- Complication: intestinal obstruction, infarction
235
What does intussusception in adult vs infant mean?
- Infant usually is no underlying pathology. More common in SB.
- Adult: signifies increased intraluminal mass or tumor
236
Volvulus. In children, what location is it most frequent in? In adults?
- children: SB
| - adults: SB and LB
237
What does steatorrhea mean?
- Malabsorption of fat
238
Causes of malabsorption. What is most common in US?
- Celiac sprue, tropical sprue, Whipple Disease, Lactase deficiency, Abetalipoproteinemia
- Most common in US: Celiac sprue, chronic pancreatitis, Crohn dz
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Consequences/manifestations of malabsorption
- diarrhea, flatus, abdominal pain, weight loss
- anemia, bleeding
- osteopenia, tetany
- amenorrhea, impotence, infertility, hyperparathyroidism
- purpura, petechiae, edema, dermatitis, hyperkeratosis
- peripheral neuropathies
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What is celiac sprue? Pathogenesis? Histological findings? Diagnosis?
- Gluten-sensitive enteropathy
- Path: gliadin exposure, genetic susceptibility (DQ2, HLA-B8), T-cell mediated inflammation
- Histo: proximal villous atrophy/blunting
- Dx: history, biopsy, response to diet
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What is tropical sprue?
- Malabsorptive dz found in tropics (india, Caribb, Africa, SE asia, central and S America) that affects entire SB as a result of infection. Leads to folate/and or B12 deficiency.
- Tx with abx
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What is Whipple disease? Signs/symptoms? Which group is mostly affected? Hallmark findings histologically?
- It is a bacterial infection - systemic disorder that has a malabsorptive component.
- Systemic: intestinal, CNS and joint involvement.
- SSx: severe malabsorption, diarrhea, steatorrhea, emaciation, fever, polyarthritis
- Histo: macrophages PAS pos with Tropheryma whippelii (gram pos actinobacteria) in areas affected (skin, SB, CNS, joints, brain, lungs, kidney, LNs, spleen, liver)
- Tx: abx
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Where is the most common location for bowel tumors? What type of tumor?
- Colon
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What is the most common tumor of the GI tract?
- Epithelial in origin. Majority (70%) = adenocarcinoma
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What are the most frequent tumors of small bowel?
- Benign: adenomas (these are pre-malignant), mesenchymal tumors (GISTs)
- Malignant = less frequent = adenocarcinomas and carcinoids
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Common site of adenomas in small bowel? Presentation?
- Ampulla of Vater. Presentation = occult blood loss, obstruction or intussusception
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Adenocarcinomas. Where do most occur? What is characteristic morphologic finding? Risk factor?
- Most in duodenum
- Finding: napkin ring
- Risk: CD
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Types of polyps in colon. What is most common?
- Non-neoplastic:
a. hyperplastic polyps: benign in recto-sigmoid, most common
b. hamartomatous polyps (Juvenile, Retention and Peutz-Jeghers): normal tissue arranged abnormally, may be familial
c. inflammatory polyps (aka pseudopolyps) as in IBD (UC)
- Neoplastic:
a. adenomas (adenomatous polyps): most common (benign), precursor to colorectal CA.
o There are four types: tubular, tubulovillous, villous, serrate
b. colorectal carcinoma (incl. adenocarcinoma)
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What are hyperplastic polyps? Locations, cause and morphology? Do these have malignancy potential?
1. Hyperplastic polyps: hyperplasia of glandular tissue
a. rectosigmoid
b. decrease in epithelial cell turnover and delayed shedding (mature cells on surface)
c. well-formed glands/cysts, lined by non-neoplastic mature goblet and absorptive cells, sawtooth pattern secondary to delayed shedding. Gross: small, nipple-like polyps.
- Typically no malignancy potential
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What are hamartomatous polyps? Types? Symptoms? Locations, cause and morphology? Do these have malignancy potential?
2. Hamartomatous polyps: focal normal tissue arranged abnormally. Types: juvenile, retention and Peutz-Jeghers
a. Juvenile and retention: children
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What is Peutz-Jeghers syndrome? Describe morphological considerations? Risk?
- AD syndrome presenting with single/ multiple hamartomatous polyps and mucocutaneous pigment resulting from mutation in STK 11 gene. Genetic predisposition to cancer in colon, pancreas, breast, lung, ovary and uterus. Note: polyps themselves are not malignant.
- Polyps: CT and smooth muscle! Lined by intestinal epithelium. More common in SB, but throughout GI. Large and pedunculated.
- Risk: intussusception.
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What is juvenile polyposis syndrome?
- Disorder with increased risk of developing adenomas and adenocardinomas. Children can have juvenile polyps (hamartomatous type polyp). Increased risk is elsewhere to the juvenile polyp.
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Are adenomatous polyps (adenomas) in the GI tract malignant or benign? Are they cancer precursors? Prevalence?
- Benign. They are neoplasms and have malignancy potential. Precursors to colorectal CA.
- Prevalance: 50% > 50 years old, M=F
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What does malignancy risk of adenomatous polyps depend on?
- SIZE = most important (max diameter is chief determinant)
| - Histologic architecture and severity of dyplasia
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Four types of adenomatous (adenomas) polyps in GI. Which is the most common? Which is least likely to be malignant? Which frequently contain carcinoma?
1. Tubular adenoma: most common, least likely malignant (check stalk for invasive adenocarcinoma)
- tubular glands, pedunculated, looks like strawberry on stick
2. Tubulovillous adenoma
- intermediate shape, structure, risk of carcinoma correlates to villous proportion
3. Villous adenoma: frequently contain carcinoma (no stalk to buffer spread)
- sessile, large broad-base w/villiform extensions
4. Serrate adenoma: usually right colon
- similar to hyperplastic polyps w/ serrations
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Clinical features of adenomatous polyps.
- May be asymptomatic. Often with anemia 2nd to occult bleeding.
- Villous adenoma are more often symptomatic with overt rectal bleeding and mucus secretion
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What are intramucosal carcinomas? Do they metastasize?
- Breach basement membrane to LP or muscularis mucosa. LP invasion has little or no metastatic potential. ? about muscularis mucosa.
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Does high grade dysplasia (CIS) metastasize?
- Little or no metastatic potential
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3 histologic conditions that must be met with excision of invasive carcinoma
- Adenocarcinoma superficial, does not approach margin of excision across base of stalk
- NO vascular or lymphatic invasion
- Not poorly differentiated (poorly differentiated = signet ring as example)
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Can an invasive carcinoma arising from sessile (villous adenoma) be excised for this to be accounted for as sufficient treatment? Per slide: what is the only adequate tx for a pedunculated or sessile adenoma?
- No. Only adequate tx is complete resection.
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Describe adenoma-carcinoma sequence
- Theory that CA develops from adenomatous lesion. Data: those with high prevalence of adenomas have incidence of CA, early invasive adenomaCA often surrounded by adenomatous tissue, CA risk related to # of adenomas, incidence of CA decreases with removal of adenomas
1. Normal colon: first hit – germiline or acquired mutation of suppressor genes (APC, mismatch repair eg. MSH2 genes)
2. Mucosa at risk: second hit – methylation abnormalities / inactivation of normal alleles (APC, beta-catenin, MSH2)
3. Adenomas:
a. protooncogene mutation (K-ras)
b. homozygous loss of additional suppressor genes (p53, LOH)
4. Carcinomas: additional mutations and gross chromosomal alterations
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Risk factors for colorectal carcinoma
- Increasing age, prior colorectal CA or polyps, UC & Crohn’s dz, genetic factors, diet
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Male patient presents with IDA and is 67 yo, what is the diagnosis?
- IDA in older male is GI carcinoma until proven otherwise
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Clinical features of colorectal carcinoma
- Frequently asymptomatic.
- If left-sided: disturbances in bowel function
- If right-sided: anemia (IDA), weakness, fatigue, malaise
- Also weight loss
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What is FAP?
- Group of uncommon AD disorders that cause polyp formation with propensity for malignant transformation
- Classic FAP, attenuated FAP, Gardner syndrome, Turcot syndrome
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Describe 4 types of FAP
1. Classic FAP: mutations of APC gene
- Avg of 1000 adenamotous polyps (mostly colorectal) form. Virtually 100% develop carcinoma usually before age 30
2. Attenuated FAP: certain APC, MUTYH mutations
- Fewer polyps
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What is HNPCC?
- Hereditary non-polyposis colorectal cancer, aka Lynch syndrome
- MSH2 and MLH1 mutations – genes responsible for DNA repair. Also mutations involved in mismatch repair.
- These patients develop colon cancers (often multiple) at early age in right colon. Also increased risk for extraintestinal CA particularly endometrium. Also stomach, ovary, ureters, brain, SB, hepatobiliary tract and skin.
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Which colorectal cancers often cause obstructed?
- Left-sided – leads to pencil-thin stool
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How is prognosis of colorectal adenocarcinomas determined?
- TNM staging: depth of invasion, presence of absence of LN metastasis. This is most important.
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Which stage I-IV is cancer penetrated wall?
- from 3+
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Should we learn dukes staging?
Should we learn dukes staging?
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What is a gastrointestinal carcinoid tumor? Which metastasize frequently? Rarely? What is carcinoid syndrome?
- Neuroendocrine tumor that produce hormones including often 5HT. 5HIAA can be measured in urine.
- Most frequently = gastric and colonic (90%)
- Least = appendix and rectal
- Carcinoid syndrome: mets to liver most often times is when these symptoms are seen. Sx = flushing, diarrhea, bronchoconstrictive etc.
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What is the most common extra-nodal site of primary lymphoma?
- Gut. Most are B cell.
| - Noteably, 40% of lymphomas are extra-nodal
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Types of gastrointestinal lymphomas. Describe.
1. MALT (aka Western type): sporadic, most common in US. Anywhere in GI tract, arises from B cells of MALT. These are biologically different from nodal lymphomas in that they behave as focal tumors and can surgically resected. For relapse, only in GI tract. Most commonly associated with H. pylori.
2. Sprue-associated: seen in long-standing malabsorptive syndrome patients, usually T cell origin
3. Mediterranean: unusual B-cell lymphoma, abnormal IgA heavy chain synthesis. Referred to as immunoproliferative small intestine dz.
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What is the most common cause of primary GI lymphomas?
- Usually sporadic. If not, commonly from chronic gastritis d/t H. pylori. Many other causes, but meh!
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Most common cause of acute appendicitis?
- Obstruction (usually fecalith).
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Histologic appearance of acute appendicitis
- Neutrophilic infiltration of muscularis propria. He called it a sea of neutrophils
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Most common tumor of appendix
- Carcinoid
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Tumors of appendix
1. Carcinoid
2. Mucinous tumors and conditions
a. Mucocele: non-neoplastic, appendix enlarged, obstructed and mucin-filled
b. Mucinous cystadenoma: benign, mucin-producing
c. Mucinous cystadenomacarcinoma: enlarged appendix with mucin-filled dilated spaces, invasive cells penetrate wall – produce pseudomyxoma peritonei (mucus secreting malignant cells fill abdomen)
