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0

Mushroom ingestion and severe hepatotoxicity -- toxin and mechanism?

alpha-amantin (Amanita phalloides/death cap mushrooms)
inhibits RNA Pol II

1

What vitamin cofactor is involved in delta-aminolevulinic acid formation? What process is this?

Vitamin B6 (pyroxidine, converted to the pyridoxal phosphate cofactor)

Heme synthesis
1st step is B6 co-factor assisted conversion of:
[glycine and succinyl-CoA] to [delta-aminolevulinic acid]

2

What causes duodenal atresia? What causes intestinal atresia distal to the duodenum (jejunal, ileal, and colonic atresia)? What is the classic finding?

Duodenal atresia due to failure to recanalize (associated with trisomy 21).

Jejunal, ileal, colonic atresia due to vascular accidents in utero (they are NOT cause by abnormal fetal development and thus not congenital malformations).
- Diminished intestinal perfusion leads to ischemia of a segment of bowel, with subsequent narrowing or obliteration of the lumen (ileum most often affected).
- If a major vessel is occluded (such as the SMA), the area of intestinal wall necrosis is large. A blind-ending proximal jejunum is formed with dissolution of a long length of small bowel and absence of associated dorsal mesentary. Terminal ileum distal to atresia assumes a spiral configuration around an ileocolic vessel to form the "apple-peel deformity".

3

What is apple-peel atresia due to? What else is seen?

small bowel distal to atresia (due to vascular accident/occlusion/ischemia) assumes a spiral configuration around an ileocolic vessel

occurs in atresia distal to the duodenum (jejunal, ileal, colonic atresia)

also see blind-ended proximal jejunum with dissolution of long length of small bowel and absence of associated dorsal mesentery.

4

What part of the duodenum is associated with the ampulla of Vater (site where pancreatic and common bile ducts merge)? What part of the duodenum is associated with the uncinate process of the pancreas and SMA?

2nd part of duodenum (descending part): ampulla of Vater

3rd part of duodenum (transverse/horizontal): uncinate process and SMA/SMV

5

What does the ventral pancreatic bud form? What does the dorsal pancreatic bud form?

Ventral:
uncinate process, inferior portion of head, and main pancreatic duct of the pancreas

Dorsal: most of head (superior), body, tail, and accessory pancreatic duct

6

What is pancreas divisum?

ventral and dorsal pancreatic buds fail to fuse at 8 weeks
pancreatic ductal systems remain separate, with the accessory duct draining the majority of the pancreas (usually clinically silent, but may predispose to recurrent pancreatitis)

Normally the proximal part of the accessory pancreatic duct degenerates (or can persist as a lesser duct) and the distal portion fuses with the ventral/main duct to become the main pancreatic duct.

7

Name the structures that are retroperitoneal.

SAD PUCKER

Suprarenal / adrenal glands
Aorta and IVC
Duodenum (2nd to 4th parts)
Pancreas (except for tail)
Ureters
Colon (descending and ascending)
Kidneys
Esophagus
Rectum (partially)

8

Male infant fails to pass meconium - dimple instead of anal opening found? Association?

Imperforate anus - spectrum of disorders associated with abnormal development of anorectal structures (most often associated with fistulas, could present with meconium discharged from urethra or vagina)

Pts most often have other congenital malformations, most commonly urogenital tract anomalies.

9

Mutation in Lynch syndrome? Inheritance? Portion of colon affected? Other associations?

mutation of DNA nucleotide mismatch repair genes
autosomal dominant

affects the proximal colon / right-sided

Lynch syndrome pts also have an increased risk for ovarian and endometrial carcinoma (in addition to colorectal carcinoma)

10

What is SMA syndrome?

transverse (3rd) part of the duodenum become entrapped between the SMA and aorta, causing symptoms of intestinal obstruction

occurs when angle between aorta and SMA critically decreases, secondary to diminished mesenteric fat (e.g., loss in body weight), pronounced lordosis, or surgical correction of scoliosis

11

What is posterior to the pancreas? Is it peritoneal or retroperitoneal?

left kidney, aorta, and IVC posterior

tail is peritoneal
rest is retroperitoneal

12

What portion of the GI tract is affected by Hirschprung's? Genetic associations?

rectum is ALWAYS involved (neural crest cells migrate caudally)
sigmoid colon involved in 75% of cases

associated with mutations in the RET gene
associated with Down syndrome

13

What is the omphalomesenteric duct? Conditions associated with abnormalities and common features?

Vitelline duct that connects the midgut lumen with the yolk sac in early embryo -- involutes by the 7th week, but failure to involute could lead to:

- persistent duct
- Meckel diverticulum (true diverticulum)
- vitelline sinus
- vitelline duct cyst

common features of the above are connections to the ileum and umbilicus by a fibrous band

14

How is the lac operon suppressed in the presence of glucose? How is it activated in the presence of lactose?

glucose decreases cAMP levels; without cAMP, CAP cannot bind positive regulatory site upstream of promotor
(high cAMP levels are needed to bind CAP -- cAMP-CAP binds a region upstream of promotor to positively regulate lac operon transcription)

Lactose binds the repressor protein, which can no longer bind the operator and block transcription of lac operon genes

15

2-day-old with bilious vomiting; cecum fixed to right upper abdominal quadrant?

intestinal malrotation - due to abnormal rotation and fixation of the midgut during fetal life

- midgut normally herniates through umbilical ring at 6wks to allow rapid growth of gut and liver despite slower growth of abdominal cavity
- midgut returns to abdominal cavity at 10wks while completing a turn allowing for proper placement and fixation of intestine in abdominal cavity

Cecum found in right upper quadrant fixed with fibrous bands to the 2nd part of the duodenum; entire midgut fixed to the SMA.

Findings:
- intestinal obstruction - adhesive bands compress duodenum
- midgut volvulus - intestinal ischemia due to twisting of the intestine around the SMA

16

What tissues are found in Meckel diverticulum? What is ectopy?

two tissues:
- gastric (most common; acid secretion can cause ulceration and bleeding -- painless melena)
- pancreatic

Ectopy - microscopically and functionally normal cells/tissues found in an abnormal location due to embryonic maldevelopment

17

What do high levels of delta-aminolevulinic acid indicate? What co-factor is needed?

delta-aminolevulinic acid = intermediate in heme synthesis

VitaminB6 (pyroxidine) needed to convert succinyl-CoA and glycine into delta-aminolevulinic acid

Elevated levels of delta-ALA seen in:
- lead poisoning
- acute intermittent porphyria

18

What supplies the foregut and what structures are included? Midgut? Hindgut?

Foregut supplied by the celiac:
- pharynx to proximal duodenum
- liver, gallbladder, pancreas, spleen (mesoderm)

Midgut supplied by SMA:
- distal duodenum to proximal 2/3 of transverse colon

Hindgut supplied by IMA:
- distal 1/3 of transverse colon to upper portion of rectum

19

3-month-old with recurrent vomiting found to have pancreatic tissue encircling duodenum? Due to?

annular pancreas
due to abnormal migration of the ventral pancreatic bud

abnormally encircles 2nd part of duodenum to cause duodenal narrowing and upper obstruction symptoms

20

What kind of bias does "matching" control for? What are other means of controlling for this type of bias?

Controls for confounding bias - when factor is related to both exposure and outcome but not on the causal pathway (this factor distorts or confuses effect of exposure on outcome)

Matching variables should ALWAYS be the potential confounders of the study!! Cases and controls are then selected based on the matching variable, such that both groups have a similar distribution in accordance with the potential confounders.

Other means of controlling confounding bias:
- crossover studies (subjects act as own controls)
- multiple/repeated studies

21

Back-up of what vessels are responsible for esophageal varices? Hemorrhoids? Caput medusae? Give the anastamoses to systemic circulation as well.

Chronic portal HTN leads to dilation of small, pre-existing vascular channels between the portal and systemic circulations (back-up from portal hypertension dilates anastamoses to systemic circulation).

Esophageal varices:
portal vein pressure backs up LEFT GASTRIC (portal circulation) into esophageal veins (systemic circulation; dump into azogos vein into SVC)

Hemorrhoids:
portal vein pressure backs up SUPERIOR RECTAL VEIN (portal) into middle and inferior rectal veins (systemic)

Caput medusae:
portal vein pressure backs up PARAUMBILICAL VEINS (portal) into the superficial and inferior epigastric veins (systemic)

22

Galactokinase deficiency? Classic galactosemia?

Galactokinase deficiency:
- can't convert galactose to galactose-1P
- galactose in urine, infantile cataracts
- relatively mild

Galactosemia:
- galactose-1-P uridyltransferase deficiency
- accumulation of toxic substances like galactitol (accumulates in lens of eye)
- failure to thrive, jaundice, infantile cataracts, intellectual disability

23

MAPK pathway starts with growth factor binding and autophosphorylation of residues - what leads to activation of kinase cascade?

adaptor protein binds to P-ed receptor, leading to Ras activation (GTP/active form) that activates Raf kinase leading to MAPKK and then MAPK phosphorylation/activation

24

Meckel diverticulum vs. Zenker divertiuculum: which is true, which is false? What layers are involved?

Meckel: true diverticulum
- mucosa, submucosa, and muscular layers all in pouch

Zenker: false diverticulum
- mucosa and submucosa only

25

What is the duodenal bulb? Ulceration of the posterior wall is most likely to affect what artery?

Region of the duodenum closest to the stomach

Ulceration of posterior wall may erode the gastroduodenal artery. (Common biliary duct and portal vein also lie posterior.)

26

What is the cardiac stomach?

Upper portion of the stomach that adjoins the opening to the esophagus

Covered on one side by lesser omentum, but not the greater omentum.

27

What two ligaments compose the lesser omentum? What structures are contained between the two layers of the lesser omentum?

Lesser omentum is a double layer of peritoneum that extends from the liver to the lesser curvature of the stomach and beginning of the duodenum; divided into two fragments:
- hepatogastric ligament (connects to lesser curvature)
- hepatoduodenal ligament (connects to duodenum)

Hepatogastric -- contains left and right gastric arteries and gastric veins
Hepatoduodenal -- contains portal triad (hepatic artery, portal vein, common bile duct)

28

What does 99mmTcpertechnetate accumulation on a radionuclide scan indicate? Accumulation in right lower abdominal quadrant in 2yo girl with tarry stools suggests?

indicates presence of gastric mucosa

suggestive of ectopic gastric epithelium -- Meckel diverticulum

29

What organ is supplied by an artery of the foregut although it is NOTa foregut derivative? What tissue is it derived from?

Pancreas formed from mesoderm (mesodermal dorsal mesentery), but supplied by splenic artery, a branch of the celiac trunk (primary blood supply of the foregut)