GIT EMBRYOLOGY

352

 Umbilical hernia vs. omphalocele vs. gastroschisis

o Umbilical hernia  due to incomplete closure of the umbilical ring
o Omphalocele & gastroschisis  failure of the herniated abdominal
content to be reduced.
o Umbilical hernia is usually reducible, asymptomatic. Usually
protruded during crying or straining

353

1
 Intestinal stenosis / atresia :
 Same clinical finding as mid-gut volvulus (mist be excluded first), but the
more distal the lesion, the more to be distended rather than emesis.
 Due to vascular occlusion in utero → ischemia of the bowel, associated with
gastroschisis
 Lead to absence of a large portion of the small intestine associated with
dorsal mesentery , the distal portion of the intestine assume a spiral
configuration around the ilio-colic vessels (apple peel / Christian tree
appearance”

2
 CHPS → due to hypertrophy of the pyloric muscularis mucosae, narrowing is
exacerbated by local inflammation & edema

 Spleen is mesodermal organ (dorsal mesentery) but supplied by foregut blood

vessels

 Annular pancreas:
 Normal development: ventral pancreatic bud developed at 5th week of
gestation, at 7th week it rotate behind the 2nd part duodenum to fuse with
the dorsal bud at the 8th week.
 Abnormal migration of the ventral bud → annular pancreas, due to
adherence of the bud to the duodenum or dorsal bud before rotation
 Clinical picture : asymptomatic, pancreatitis (due to pancreatic duct
obstruction), duodenal obstruction

3
 Clinical picture of pancreatic divisium? Most of patients, it is clinically silent,
may predispose to recurrent pancreatitis, there are two main duct
systems that drain different portion of the pancreas

 Omphalo-mesenteric Duct (Vitelline duct):

o Normally obliterated by 7th week
o Persistent vitelline duct = Vitelline fistula
o Incomplete closure = vitelline sinus
 What is the enterocyst? It is the vitelline duct cyst

 Clinical picture of patent urachus:

- Straw colored urine discharge from the umbilicus, exacerbated by crying,
straining, prone position associated with local skin irritation

4
 GIT ANATOMY
354

355
 If the liver continue to bleed after Pringle’s maneuver → IVC or hepatic veins
are the sources of bleeding

5
356

 Anatomical relation of different parts of duodenum:

- 1st part → pass horizontally over L1, intra-peritoneal
- 2nd part → pass inferiorly from L1 – L3, related to head of pancreas,
CBD, ampulla of Vater
- 3rd part → horizontally over L3, related to aorta, IVC, SMA, uncinate
process
- 4th part → pass superiorly to the left of L2 – L3, Ligament of Treitz

 Normal histological appearance of esophagus:

6
 Surgical landmark for the appendix: the tinea coli begin as continuous layer of
longitudinal muscle that surround the rectum just below the serosa, at the
recto-sigmoid junction it condensed to be 3 distinct longitudinal bands
souuround the colon that converge at the root of appendix. (has the same
function as the outer layer of muscularis externa)

357
 Horizontal transection of the rectus abdominus carry the risk of?
Superior & inferior epigastric arteries supply the rectus abdominus, inferior
artery pass posterior to the rectus abdominus at the level of the arcuate line →
injury lead to significant hematoma due to loss of the the supporting posterior
rectus sheath.

7
8
 Common iliac artery branches (before passing inguinal ligament) :
 Inferior epigastric artery (pass medially, superiorly)
 Deep circumflex iliac artery (pass laterally)

 Renal vessels:
o Right renal : shorter, vein runs in front of artery, right gonadal vein
drain directly into IVC
o Left renal : longer, vein run between aorta & SMA causing its
compression “Nutcracker effect” → ↑↑ pressure in left renal vein (left
testicular vein drain in the renal vein) → Varicocele ; this why
varciocele occur more on the left
 What is the origin of the left gonadal artery?
- Abdominal aorta not left renal artery ☺

 superior mesenteric artery syndrome :

 normally angle ~ 45o, in the syndrome the angle is < 20o
 the 3rd part duodenum & left renal vein get entrapped
 causes: any condition ↓↓ mesenteric fat (e.g. weight loss, burn, catabolism,
9
 bed rest), ↑↑ lordosis, after surgical correction of scoliosis (lengthen the
spine→ ↓↓ mobility of superior mesenteric artery)

 IVC is formed by union in common iliac veins at level of L4-5; it enters the
thorax at level of T8 (VOA – 8/10/12)

 Where are the watershed areas of GUT: splenic flexure (between superior
mesenteric artery & IMA) & recto-sigmoid junction (sigmoid artery &
sup. Rectal artery)

 Ligament of treitze

358
 Which branches supplied by splenic artery will be most affected by splenic
artery occlusion. Short gastric arteries as they have very poor anastomosis,

10
 unlike left gastro-epiploic artery which is has strong anastomosis.

 Causes of liver infarction due to hepatic artery embolization? Should be

considered in transplanted liver as collateral circulation is severed during the
operation.

 Clinical picture of splenic laceration: circulatory collapse, Kehr sign

(peritoneal irritation → reffered left shoulder pain, hiccups)

359
 Gastric varices:
o Portal hypertension cause ↑↑ pressure in the left gastric vein → both
gastric & esophageal varices.
o Superior mesenteric vein → cause varices in the lower stomach
o Splenic vein thrombosis (due to chronic pancreatitis, tumors, pancreatic
cancer) → ↑↑ pressure in short gastric veins → fundal varices only with
normal esophagus, rest of the stomach.

 Splenic Vein Thrombosis – affects short gastric veins draining antrum of the
stomach, producing gastric (fundal) varices only

11
360
 Lymphatic drainage of the rectum : either internal iliac or inferior
mesenteric
→ Either in bowel wall (epicolic), around arterial arcades (paracolic), around
mesenteric vessels (intermediate)
→ 1 site of nodal metastasis are the sentinel lymph nodes first 1-4 nodes
st

drain specific colon segment.

 Upper 1/3 rectum: superior rectal nodes → inferior mesenteric lymph
nodes
 Middle & lower 1/3 rectum: either upward into inferior mesenteric
lymph nodes or middle rectal → internal iliac LNs.
 Below dentate line: mainly to inguinal lymph nodes, may reach inferior
mesenteric & internal iliac lymph nodes
 Left colic lymph nodes → drain hepatic flexure and upper descending
colon.

12
 Anastomosis between IMS & SMA :
 SMA & IMA are the main blood supply of the small & large intestine.
 Many anastomosis connect them.
a) Marginal artery of Drummond (principal)
b) Arc of Riolan (mesenteric meandering artery)
 So IMA is not always reconnected during aneurysmal repair
 N.B. IIA & EIA make anastomosis with other arteries to supply the
rectum, abdominal wall

 Internal hemmorhoids are autonomically innervated from the inferior

hypogastric plexus → sensitive to stretch not pain

13
361

362
 Alkaline phosphatase  present in liver, bone, placenta, intestine, kidney,
leukocytes, and neoplasm. Threefold elevation in ALP = liver disease.
Moderate elevated ALP  GGT

 Superficial inguinal lymph nodes drain all skin below the umbilicus except
testis (para-aortic) & posterior calves, glans penis (deep inguinal LNs)

 Femoral triangle:
 Femoral artery → mid-inguinal point (midway between pubic tubercle,
ASIS)
 Femoral vein cannulation → ~ 1 cm below the inguinal ligament, ~ 1 cm
medial to femoral artery pulsation

14
363

364

 Groin hernia :
a) Direct & indirect hernia occur above the inguinal ligament, while the
femoral hernia occur below it
b) emoral hernia is more common in ♀ & tend to occur on the right side.
Direct hernia Indirect hernia
Protrusion through triangle Failure of obliteration of
of Hasselbach. process vaginalis
Less prone to incarcerate More common, more on Rt.
side
Less prone to descend to Better felt by tip of finger
scrotum
Best felt with pulp of finger

15
 Causes of direct inguinal hernia:
 As the floor of HAsselbach’s triangle is formed of tranversalis fascia …
breaking down of this fascia either by chronic wall injury or CT abnormality
→ protrusion & direct inguinal hernia

 Testicular descent :
- occur slowly from week 8 – full term, palpable testes at inguinal canal
mostly descend spontaneously at age of 6 months
- The deep inguinal ring is an opening in the fascia transversalis lateral to the
inferior epigastric vessels and superior to the mid-inguinal point (midway
between the ASIS and the pubic tubercle).
- The superficial inguinal ring is an opening in the external oblique muscle
aponeurosis and lies above and medial to the pubic tubercle.
- The conjoint tendon is the common tendon of the transverses abdominis
and internal oblique muscles. It forms part of the posterior wall of the
inguinal canal.

16
 GIT PHYSIOLOGY
365
 Cholecystokinin → responsible for secretion of enzymes from acinar cells
While secretin responsible for secretion of fluid rich in HCO3 & poor in Cl to
neutralize the acidity from stomach (with no effect on enzymes production)

 Somatostatin is originally produced from hypothalamus to ↓↓ GH production.

Somato-statin-oma can cause either ↓↓ or ↑↑ glucose, ↓↓ cholecystokinin → gall
stone

 Physiology of Deglutition (swallowing):

366
 Gastric acid secretion :
 Histamine → H2 receptors ∷ ↑↑ cAMP
 Ach → M3 ∷ ↑↑ IP3
 Gastrin → CCB receptors ∷ ↑↑ IP3
→ ↑↑ Histamine though ECL cells
 Neutralization of the gastric acidity:
1) Brunner glands in the duodenum: most numerous at the pylorus, may be
found in ampulla of Vater, the ducts of these glands extend through the
muscularis mucosa and termiate in the crypt of Lieberkuhn
2) Pancreatic ductules: produce watery secretions containing ↑↑ concentration
of bicarbonate ions, emptied in the duodenum
 gastric acid secretion:
 there are 3 phases of gastric acid secretion.
1) Cephalic phase: stimulated by smell & taste of food, mediated by vagal
stimulation
2) Gastric phase: stimulated by chemical irritation of the stomach,
mediated by gastrin & histamine (from ECL cells)
3) Intestinal phase: very minor role in gastric acid secretion. Ileum & colon
produce peptide YY → inhibit ECL cells → ↓↓ gastric acid production.

367
 Trypsinogen is activated in the duodenum by its brush border enzyme
enteropeptidase → deficiency cause protein & fat malabsorption→
diarrhea, Failure to thrive, edema
17
 Pancreatic fluid is isotonic, contain same amount of Na, K as ECF. Due to
action of secretin → ↑↑ HCO3 & ↑↑ pancreatic juice flow SO in High flow
→ ↑↑ HCO3, Low flow → ↑↑ Cl (‫ )الطبيعي‬ chloride & HCO3 are exchanged
at the apical surface of pancreas, so ↑↑ HCO3 lead to ↓↓ Cl and vice versa

18
368
 notice some characters of vitamin B12 absorption

369

19
20
 GIT PATHOLOGY
370
 Suppurative parotitis : note that post-surgical or post-intubation due to lack
of salivation an dry mouse, may be complicated by infection

 Manometer patterns in esophageal diseases:

o Achalasia : ↓↓ amplitude of peristalsis in mid esophagus, ↑↑ tone &

incomplete relaxation at LES
o Scleroderma : ↓ in LES & peristalisis
o Cricopharyngeus dysfunction → chocking, food sticking sensation on
swallowing

21
371

 Mallory Weis syndrome :

 Other causes : + repeated abdominal strain, trauma, hiatal hernia (50%)
 Very common cause of hematemesis 10%, never life threatening

 pathogenesis of diffuse esophageal spasm → impaired inhibitory neuro-

transmission within the esophageal myenteric plexus

 Crico-pharyngeal motor dysfunction → cause Zenker diverticulum → early

dysphagia, obstruction, +/- pulmonary aspiration

 What are the traction diverticulae and its causes:

 Created by inflammation & scarring of the gut wall → pulling &
outpouching of all gut layers. Ex. I midesophagus due to pull by
inflammatory mediatinal lymphadenitis.

 New onset odynophagia in setting of GERD → progression of the

GERD into erosive esophagitis or ulcer formation (need Upper
endoscopy), Barrett’s esophagus is asymptomatic

22
 Cause of reflux in scleroderma  esophageal dysmotility (not uncoordinated
motility) due to atrophy & fibrous replacement of the muscle → LES become
atonic & dilated

 Histology of GERD (detailed):

 Patients may have silent disease with extra-esophagus manifestations
 Basal zone hyperplasia
 Scattered eosinophil & neutrophils
 Basal zone hyperplasia

Barrett esophagus

23
372
 Risk factors of esophageal cancer:

 Esophageal carcinoma : prognosis is usually poor due to late diagnosis

 Histological appearance of SCC :

o Nests of squamous cells with abundant eosinophilic cytoplasm &

distinct borders

24
 o Areas of keratinization “keratin pearls” (arrows)
o Inter-cellular bridges (picture)

 Leiomyoma : most common benign tumor; fascicles of spindle cells with

fibrosis

 Reflux esophagitis: elongation of basal papillae, basal cell hypertrophy, intra

epithelial eosinophils

 Barrett’s esophagus : intestinal metaplasia → coloumnar epithelium with

goblet cells >>> goblet cells

25
373

Stress-Related Mucosal Disease –

acute gastric mucosal defects caused by severe physiologic stress (e.g. shock,
extensive burns, sepsis, severe trauma, intracranial injury),
impaired mucosal protection due to local ischemia from systemic hypotension and
splanchnic vasoconstriction produces multiple, small (<1 cm), circular lesions in
stomach ranging from superficial erosions to full-thickness ulcers, which may
perforate or bleed,
types:
1.) Curling’s Ulcers: arise in proximal duodenum in association with severe trauma
or burns,
2.) Cushing’s Ulcers: arise in esophagus, stomach, or duodenum in patients with
intracranial injury, particularly prone to perforation, caused by direct vagus nerve
stimulation due to elevated intracranial pressure, resulting in increased ACh
release and hypersecretion of gastric acid (“Burned by the Curling iron, always
Cushion the brain”)

26
 Pathogenesis of pernicious anemia :

 Why H.pylori cause duodenal ulceration:

 H. pylori → urease positive: convert urea to alkaline ammonia → injury to
the gastric epithelium → local inflammation → depletion of antral D-cells
(somatostatin) → ↑↑ gastrin → ↑↑ acidity
 H. pylori → cytotoxin that ↓↓↓ production of the bicarbonate
 Why H.pylori cause gastric ulcer & cancer:
 H.pylori → urease positive: convert urea to alkaline ammonia → injury to
the gastric epithelium → local inflammation → ↓↓ parietal cells (body)
27
  Direct mucosal damage caused by bacterial products → metaplasia &
damage

 Duodenal ulcer: although the ulcer in duodenum, H. pylori is preferentially

affect the antrum (with ↓↓ somatostatin level) with very low conc. Of the
bacteria in duodenum
 In contrast gastric ulcer is not due to ↑↑ acidity (rather due to direct mucosal
damage and inflammation) … colonization is present in the gastric body
 NSAIDs and GI bleeding:
 2 mechanism : 1) ↓↓ PG E2 2) ↓↓ platelet aggregation
 Risk of GI bleeding ↑↑ even with low dose aspirin by 2 – 3 folds
 Histological appearance of chronic H. pylori gastritis
Contain lymphocytes, lymphoid follicles, plasma cells

 Stress related mucosal injury → multiple, small circular lesion ranging from
erosion to full thickness ulcers. Due to local ischemia

 Gastric Bypass and Gastric Bands

28
 Gastric adenomcarcinoma :
 Intestinal type: resemble colon carcinoma, consists of columnar &
cuboidal epithelium grow as polipoidal mass inside the lumen of the
stomach
 Signet ring type: doesn’t form any glands; with cells contain abundant
mucin droplets (signet ring cells), tend to infiltrate the stomach wall due to
loss of E-cadherin → Linitis plastica.
 Most important factor that control survival is degree of wall infiltration &
regional lymph nodes

374
 Zollinger Elison syndrome :
o Ulcers beyond duodenal bulb suggest ZES
o Normally, secretin inhibit the gastrin release & ↑ pancreatic release → ↑↑
gastri after secretin = ZES (gastrinoma)
 Clinical picture of ZES:
 Peptic ulcer refractory to therapy, diarrhea≫≫ as gastric acid damage
intestinal epithelium and inactivate pancreatic enzymes
 Investigations must directed toward exclusion of MEN 1 as Most ZES are
sporadic, 20 – 30% of them are associated with MEN1 syndrome

375
 Malabsortion :
 Although it is classicaly cause steatorrhea, it may cause anorexia, weight
loss,fatigue …etc.
 Because fat have the most complex pathway fro absorption, it is the
earliest & ost severly affected in generalized malabsorption →

29
 testing for fat malabsorption is the most sensitive strategy for screening.
 Qualitative assay of stool by sudan III stain is important

 Celiac disease:
 L/M: villous atrophy, crypt hyperplasia, intra-epithelial lymphocytic
infiltration
 Age of onset 6 – 24 month.
 Malabsorption occur due to atrophy of villi → ↓↓ area for absorption
especially in duodenum & proximal jujenum

30
 Small intestinal bacterial overgrowth (SIBO):
 Enteric bacteria cause :
1) ↑↑ production of vitamin K, folate
2) Inhibit proliferation of pathogenic bacteria
3) Digest unabsorbed sugars
 SIBO → ↑↑ vitamin K & folate level, although it cause malabsorption of fat
soluble vitamins (DEKA)

 Lactose intolerance :
o Prevelant in Asia & Africa population
o Other causes :
1) Primary lactase defieicny : Normal histological appearance
a. Hereditary : rare AR disease
b. Acquired due to lactose non persistence (↓↓ lactase
producton by md childhood) common in Asians 90%,
Africans and Hispanic
2) Acquired inflammation → bacterial overgrowth, infectious
enteritis, Crohn’s disease

 Whipple disease:
 Caused by gram positive actinomycete → proliferate only within
macrophages with no inflammatory response
 Show PAS +ve granules, diastase resistant granules (consist of lysosomes
& partially digested bacteria)

376

31
 Enteric oxaluria (Crohn’s disease)
 Normally, intestinal oxalate bind to calcium to form insoluble Ca+ oxalate
that excreted in feces.
 In CD  diseased terminal ileum → ↓↓ bile acid absorption → ↓↓ fat
absorption → fat in the intestine bind to the free calcium to be
excreted in the stool, leave the oxalate frre without calcium → absorped
→ oxlalate stones

 Toxic megacolon :
 UC ≫ CD, C. difficile, other inflammatory colitis
 Transmural inflammation → release cytokines & inflammatory mediators
→ colonic SM paralysis  rapid distension, thinning wall, perforation
 Diagnosis need X-ray  colon dilatation, multiple air-fluid level, free air
 Barium enema and colonoscopy are contraindicated

32
 Gross picture of Crohn’s disease:
 Although rectum is usually spared, perianal diseases are very common
 Bowel wall thickening (due to transmural inflammation)
 Cobble stone appearance (serpeginous depressed ulcerations with normal
healthy mucosea in between)
 Creeping fat (mesenteric fat become wrapped around the colon)

 Short bowel syndrome: massive small bowel resection & Crohn disease → ↓↓
in absorptive surface area → postprandial voluminous diarrhea

 what is Paneth cell metaplasia:

 Paneth cells present normally in the instetine in the crypts of LiberKuhn
with large eosinophilic cytoplasm
 Metaplasia occur in CD (and other IBD) , may be pre-neoplastic
33
 Dumping syndrome: after gastric bypass surgery, emptying of hyperosmolar
chime into small intestine → rapid shift of fluid from serum to intestine →
postprandial GIT, vasomotor symptoms

377
 Pathogenesis of acute appendicitis:
 Luminal obstruction is the first inciting event (either by fecolith, lymphoid
hyperplasia…. Etc.) → retained mucus & distension of the appendix →
halting the venous circulation & resultant hypoxia to the wall → bacterial
invasion 
 Appendicitis:
 Visceral pain → luminal distension, stretching of smooth muscle; refered
by T10
 Somatic pain → due to irritation of parietal peritoneum

378

34
 Pathogenesis of Hirsch-sprung disease :
o Migration of neural crest cells begins at 8th week (proximal colon), migrate
along vagal nerve fibers completed by 12th week (rectum)
o Cl/P : bowel is filled, rectum is empty, tone f anal sphincter is increased
o Sigmoid colon affected in 75% of cases, but rectum and anus always
involved

35
 Meckel’s diverticulum:
 Clinical picture of Meckel’s diverticulum → gastric mucosa (being the
commonest) → hematochazia & melena, pancreatic mucosa (2nd most
common)
 When vitalline ducts obliterate? Week 7

 Heterotopy / ectopy / choristoma → normal functioning cells present in

abnormal location e.g. Meckel’s diverticulum (commonest is gastric mucosa)

 Describe the pertechnetate scan for diagnosis Meckel diverticulum:

 The Tc-ertechnetate has high affinity for parietal cells of the gastric mucosa
 ↑↑ uptake of the dye in the peri-umblical region or RLQ is characteristic for
Meckel diverticulum

379
 Malrotation and midgut volvulus :

36
  The gut herniate through the umbilicus at week 6, re-enter the abdominal
cavity after 270o counter-clockwise rotation. At week 8 – 10 week. The gut
is normally fixed to the wall by wide based mesentery
 In mal-rotation, the caecum is present at RUQ instead of RLQ with
persistant of Ladd’s band (pass from the caecum and right colon to
retroperitoneum encircle 2nd part duodenum)

380

 Necrotizing entero-colitis (NEC) :

 X-ray curvilinear lucent line that are parallel to the lumen indicate
pneumatosis intestinalis
 Upon introduction of oral feeding → food enter the colon → bacteria
proliferate due to absence of intestinal bacteria →ischemic necrosis
 30% mortality

 Clinical picture of typhoid fever:

 Feco-oral transmission → penetrate the gut mucosa via phagocytosis by M-
cells → intracellular survival → bacteremia
 Dissemination to lymphoid organs → HSM, ulceration of Peyer’s patches →
GIT bleeding, may lead to perforation

 Clinical picture & diagnosis of chronic mesenteric ischemia:

 “Very” painful epigastrium within 1 hour of the food intake, not respond to
antacids
 Doppler & CTA show severe stenosis in the celiac & mesenteric arteries

37
 Complications follow the gastro-jujenostomy operation: iron deficiency
anemia will occur as iron is absorbed mainly in duodenum & proximal
jujenum, also malabsorption of Vitamin D, B12, Calcium

381
 Colonic polyps:

 Polyps > 4 cm is more likely to malignantly transformed.

Tubulo-villous polyp
Serrated polyp

 Hyperplastic polyps: well differentiated crypts and glands that look

normally in appearance. Usually asymptomatic.

 Hamartomatous polyp : normal structures in the colon, normally

doesn’t exisit eg. Smooth muscle fibers.
May cause bleeding, intussusception

38
 Signet ring carcinoma : signet ring means clear cytoplasm with
peripherally located nucleus

 Carcinoid tumor : insular and trabecular masses of monotonous small

rounded cells with peripheral palisading,finy granular cytoplasm,
small nuclei , salt & pepper chromatin

 Villous adenoma: long like villi extending from the surface, often large
& sessile.
Can cause watery mucus diarrhea, electrolyte imbalance.

39
  Tubular polyps: small, pedunculated. Consists of dysplastic colon cells in
tubular architecture.

 Tubulo-villous adenoma:
Pic. 1 (villous) pic. 2 (tubular component)

382
 Colon carcinoma :
o Right colon : IDA, nonspecific symptoms
o Left colon : IO, change in bowel habits (alternating constipation &
diarrhea is characteristic for IBS)
o Recto-sigmoid : hematochazia
o Rectum : tenesmus, small caliber stool
40
 Mention the difference between cancer associated CRC & sporadic CRC in
terms of age of onset, origin, location, multifocality histoly & mutations

383

41
 Mutation of APC gene of 5q → ↑↑ β-catenin → uncontrolled cell proliferation.
 Adenoma carcinoma sequence (other gene abnormalities):
 Inhibition of caspases → cysteine proteases that essential in apoptosis
 Increased activity of COX-2 enzyme → found in many forms of colon
cancer & inherited polyposis syndromes
This may be due to need for PGs → epithelial proliferation
Regular aspirin intake is associated with ↓↓ risk of colon cancer

42
 Pathogenesis of ascites in cirrhosis :
 Mechanical compromise of the portal venous blood, ↑↑ vasoactive peptides
→ vasodilatation of splanchnic vessels & vasoconstriction of the systemic
vessels  ↑↑ portal vein hydrostatic pressure
 vasoconstriction of systemic vessels → RAAS → Na & H2O retention →
more ascites

 Hyperesternism of liver cirrhosis :

o spider angiomata :

43
  Due to estrogen effect on arteriolar dilatation.
 Correlate with the severity of liver diseases
 SHBG → produced from liver + uterus / testis

384
 Pathogenesis of Reye’s syndrome :
 Hepatic dysfunction: with vomiting, hepatomegaly and all lab finding of
hepatitis but no jaundice, it show microvesicular steatosis (small fat
vacuoles in the cytoplasm)
 Encephalopathy: due to the hepatic dysfunction & hyperammonemia

 Liver failure: an important determinant of prognosis of patient is liver

functional reserve, which can be detected by serum albumin &
prothrombin time levels

385
 Mechanism of hepatic encephalopathy: ↑↑↑ ammonia in the blood → altered
amino acid transport across BBB, ↓ neuro-transmitter metabolism  ↑↑
GABA, ↓↓ glutamate

 Any liver disease, notice the relation & ratio between AST, ALT… it
may be the clue

 Hepatitis A virus:
o Outbreaks usually from contaminated water, food, steamed shellfish (USA)
o Clinical picture : children  mostly silent or anicteric, adults  severe
icteric , aversion to smoking
o Vaccine → given to high risk peoples, unvaccinated contact
 Hepatitis D virus :
o It resemble the Dane particle of HBV
o HDAg – replication defective as it must be coated by the external coat
HBsAg to penetrate hepatocyte either super/Co-infection
 Clinical picture of acute hepatitis B virus:
 Incubation period ~ 3months
 May develop serum sickness like syndrome + RUQ pain
 Extensively ↑↑ AST & ALT, mostly non-icteric hepatitis
44
  +/- ↑↑ PT = poor prognosis

 Histo-pathology of acute viral hepatitis (all of them give the same picture)
 Panlobular lymphocytic infiltrates
 Ballooning hepatocytes
 Hepatocytic necrosis & apoptosis→ form rounded acidophilic bodies
called Councilman bodies or apoptotic bodies
 Kupffer cells → phagocyte hepatocellular debris → hypertrophy & laden
with lipofuscin pigment

 Pathological features of acute hepatitis:

 Spotty necrosis
 Hepatocyte necrosis: ballooning of the cells with cystic degeneration &
cytoplasmic emptying, +/- inter-connecting by the adjacent dead
hepatocytes by ”bridging necrosis” due to ATP depletion, disruption of
filament network
 Hepatocyte apoptosis: cell shrinkage & nucear fragmentation with
45
 eosinophilic cytoplasm (Councillman bodies), due to mitochondrial
oxidative damage
 Mononuclear inflammation : due to viral infection & death of cells
 Dark coloured urine (due to ↑↑ conjugated bilirubin) & acholic stool (↓↓
bilirubin pigments)

 Causes of hepatic abscess :

- Underdeveloped countries: usually caused by parasitic infestations
(e.g. E. histolytica, ecchinococci)
- Developed countries: ususally bacteria in 80% of cases through
 Biliary tract infection, direct invasion → Gram negative enteric bacteria
(E.coli, Klebseilla) or enterococci
 Trauma / penetrating injury → mixed aerobic and anaerobic bacteria
 Hepatic artery (systemic invasion) → usually Staph. auerus
 Portal lyemia → abdominal infectious processes e.g. appendicitis, food
borne illness → Entameba

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 Effect of rifaximin & uses :
 Action: ↓↓ bacterial RNA synthesis by binding with DNA dependant RNA
polymerase
 Non absorbable antibiotic that affect GUT flora
 Used with lactulose (↓↓ PH → ↑↑ conversion of ammonia to ammonium)
 Used in traveler’s diarrhea

386

 Why aflatoxin cause HCC (molecular mechanism):

 The most toxic aflatoxin is type B1 → P53 mutation (mostly G:C → T:A
47
 transversion at codon 249) → this risk is much higher if associated with
HBV

 L/M of hepatic hemangioma:  Hepatic adenoma :

- Most common benign liver mass
- Large well circumscribed masses
of BV, lined by single epithelial
layer

 Portal vein thrombosis  cause portal hypertension with normal liver

biopsy, as it is peri-sinusoidal process. Normal histology of the liver, no
ascites.
o Unlike Budd chiari syndrome → congestion and fibrosis (# hepatic
vein)

 Sinusoidal dilatation, peri-venular hemorrhage with acute venous outflow

obstruction within the liver (Budd Chiari syndrome )

387
 Biliary atresia:
o The baby born normal, extra-hepatic biliary tree undergo destruction
either immune mediated or viral mediated.
o Clinical picture reveal firm hepatomegaly (due to inflammation), absent or
abnormal GB
o Clinical picture & lab is consistent with obstructive jaundice
o Biopsy  IHBRs proliferation, portal tract edema & fibrosis
o Once diagnosed → Kazai operation if not death in 2 years due to biliary
cirrhosis

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388

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 What is the cause of DUbin Johson syndrome : AR disorder due to mutation in
bilary transport protein called multi-drug resistance protein 2
 Dubin Johnson syndrome :
 Due to mutation in canalicuar membrane transport protein
 The liver appears black → impaired excretion of epinephrine
metabolite that accumulates in the hepatocyte within
lysosomes.

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 Copper metabolism ******:
o Copper is absorbed in stomach & duodenum → bind loosely with albumin to
reach liver
o In liver; copper + α2 globulin  ceruloplasmin → secreted to the plasma
o Ceruloplasmin & un-absorbed copper → secreted into bile & excreted by
feces (primary route for copper excretion)
o Renal loses of copper represent 5 – 15% of daily excretion.

 Hallmark of the CNS findings in Wilson disease: progressive neurological

disorder with cystic degeneration affecting the putamen
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 Kayser Fleischer ring can be seen in disease other than Wilson disease?? May
be seen in chronic cholestatic iseases as PBC

 Role of HFE gene in iron transport & hemosiderosis:

 HFE protein form a complex with transferrin receptor (which uptake the
iron-transferrin complex & sense the free iron pool in the liver)
 When free iron pool reach the desired level & sensed by transferrin –HFE
→ liver produce hepcidin which inhibit DMT1 (divalent metal tansporter)
on the intestinal surface → ↓↓ iron absorption.
 In hemochromatosis, defective HFE gene → defective sensing the
hepatic iron pool → ↓↓ hepcidin, ↑↑ DMT1 → ↑↑ iron absorption  ↑↑
ferritin (storage protein), ↑↑ transferrin saturation (iron transporter I the
plasma)

 Hemochromatosis :
o First clinical picture appear when total iron > 20 g

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 o Clinical picture include atypical arthritis (psudogout), hypogonadism
o ♀ protected from early onset due to blood loss in menses, pregnancy
o Hisotloogical picture differentiate iron from lipofuscin by perussian blue
stain.
 Hemosiderin contain ferrous → turn blue on stain
 Lipofuscin don’t contain ferrous → don’t turn blue
 Both appear brown deposits

 Some extra characters of hemochromatosis :

- It cause impotence and arthropathy
- Lab : > 50% saturation of transferrin.

 Primary biliary cirrhosis:

 Dense portal tract infiltrate of lymphocytes, macrophages →
granulomatous destruction of intra-hepatic interlobular bile ducts
(florid duct lesion)
 Appear insidiously in middle aged ♀ by fever & pruritus that worse at
night
HSM, cholestasis → fatty mal-absorption & ↓↓ cholesterol excretion →
hypercholesterolemia
 Primary biliary cirrhosis:
 Jaundice is not a must, cholestatis may appear initially with ↑↑ cholesterol
& ALP
 Diagnosis is confirmed by anti-mitochondrial IgM
 Associations: (+) autoimmune thyroid diseases, hypothyroidism,
Raynaud’s $

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 Histological features of GVHD in liver :
 Similar to PBC: lymphocytic inflammation, destruction of IHBR, necrosis
of periportal tissues, granulomas & bile staining
 GVHD → commonly affect skin, liver, GIT

390

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 Cholesterol excretion is done by 2 different mechanisms :
1) Conversion into bile acids: cholesterol is changes to bile acids → bile salts
2) Free insoluble cholesterol:
 ↑↑ free cholesterol & ↓↓ bile salts  precipitation of formation of
cholesterol stones

 Describe the pathogenesis of acute calcular cholecystitis:

 Begin by longstanding gallbladder outflow obstruction → hydrolysis of
lecithin → ↑↑ Lysolecithin → disruption of the protective mucosal layer
 Bile salts act as detergent to the exposed luminal epithelium → chemical
irritation & prostaglandin release
 These changes → hypo-motility of the GB → accumulation of the content &
↑↑ internal pressure → ischemia & bacterial invasion of the wall.

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 Characteristics & composition of pigment gall stones:
- Usually significant number, small speculated and friable
- High amount of calcium carbonate & phosphate → often radio-opaque on
x-ray

 Pathogenesis of pigment gall stones:

- Causes involve ↑↑ unconjugated bilirubin in bile → calcium bilirubinate
deposition
- Associated with biliary tract infection due to ↑↑ β glucuronidases from
injured hepatocytes (brown stone), chronic hemolysis, ↑↑ enteroheaptic
cycling of bilirubin due to ileal disease

 Obstructive and non-obstructive cholestasis biopsy show

deposition of bile pigments within hepatic parenchyma, with
green-brown plugs in the dilated bile canaliculi

 TPN cause gall stones as ↓↓ enteral stimulation → ↓↓ CCK release → biliary

stasis & cholesterol deposition

 Diagnosis of acute cholecystitis :

 The U/S is the preferred initial diagnostic test if added with signs of
infection, inconclusive U/S → HIDA scan become the most specific one for
diagnosis of acute cholecystitis.
 HIDA scan :
Radiotracer is injected IV → taken by the liver and excreted by the bile
Image a, b → failure of the visualization of the gall bladder
Image c → visualization of the gall bladder.

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 Biliary sludge:
 Gall bladder hypomoility → ↑↑ dehydration of the bile → precipitation &
accumulation of materials → sludge (GB mud)
 Cholecystokinin cause only partial & slow emptying of the GB
 Biliary sludge is a known precursor of cholesterol stones, cause biliary colic,
cholecystitis also.

 Gallstone ileus :
o Cause intermittent bowel obstruction, till it reach ileo-cecal valve →
cause complete SBO
o Pneumobilia is also exisit

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391
 Hereditary pancreatitis :
 Trypsin is secreted in inactive form, premature activation of trypsinogen =
acute panceatitis.
 Multiple mechanisms to avoid the premature inactivation
1) Production of serine peptidase inhibitor Kazal type 1 (SPINK 1)
act as trypsin inhibitor. Mutation of this protein cause rare hereditary
panceatitis
2) Trypsin can act as its own inhibitor → by cleaving active trypsin.

 Risk factors for pancreatic cancer: (+) smoking (the most important
environmental factor) , MEN syndrome , Peutz-Jeuher syndrome, Lynch
syndrome

 Acute pancreatitis:
 Premature (intra-cellular) activation of trypsin is due to acinar damage
either directly or due to impaired blood flow
 80% of cases are due to stones, alcohol. 20% are other causes (+)
sulfasalazine, coxackie virus, M. pneumonie, structural abnormalities in the
pancreas
 Hypertriglyceridemia :
- ↑↑ TGs → ↑↑ FFA (normally bind to albumin)
- If TGs > 1000 → beyond binding capacity of albumin → FFA directly
injured the pancreatic acinar cells

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 Pancreatic pseudo-cyst:
o Unlike true cysts lined by epithelia cells, pseudo-cysts lined by granulation
tissue and fibrosis
o Mature psudocyst → after 4 – 6 weeks become fibrotic wall
o Mostly at lesser curvature

 Vitamin A cause differentiation of specialized epithelium , its deficiency cause

squamous metaplasia of the mucus secreting cells (as in pancreatic duct)

 Carcino-embryonic antigen (CEA):

 Glycoprotein involved in cell adhesion, normally produced by embryonic
pancreas, liver, intestine, present in minute amounts in healthy
adults
 Elevated in : (+) benign diseases e.g. IBD, COPD, cirrhosis, pancreatitis,
smokers
 Initial ↑↑ in CEA in colon cancer associated with poor prognosis

 Alcohol induce pancreas to secrete protein rich fluid that precipitate inside the
pancreatic ductules and plug the duct → calcify
Chronic alcoholic cause macrocytosis even in absence of anemia

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59
 GIT PHARMACOLOGY
392
 Adverse effects seen after discontinuation of PPI :
Long use of PPI → ↓↓ H secretion → ↑↑ gastrin roduction → ↑↑ parietal cell
hypertrophy. Sudden withdrawal of PPI lead to rebound gastric aci
hypersecretion & recurring of symptoms so PPI must be
tapered slowly
 Indications for use celecoxib: any patient need aspirin but have PUD or
bleeding tendency as celecoxib have potent anti-inflammatroy properties but
without these effects

393
 Misoprostol → used for NSAIDs induced peptic ulcer

394

 Treatment of chemotherapy induced vomiting:

1) Ondansteron : ↓↓ vagus mediated N & V, block central serotonin
receptros in area postrema
2) Dopamine (D2) antagonists
3) NK-1 receptors antagonsis

 Physiological causes & treatment of nausea & vomiting:

 Use of anti-emetic depends on the source of emitogenic
stimulus.
 Gastro-intestinal irritation: N & V due to gastric irritation (e.g.
infection) lead to ↑↑↑ serotonin production → ↑↑ 5-HT3 receptors  best
treated with ondansteron

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 Vestibular nausea: due to irritation if the cochlea & vestibule (e.g.
motion sickness, vertigo) → activation of H1 & M1 receptors in the inner
ear  best treated with muscarinic antagonists, anti-histaminincs
 Centeral nausea: due to irritation of D2 receptors in CTZ (in area
postrema) e.g. in migraine  best treated by anti-dopaminergic
drugs, ondansteron → if not effective, add NK 1 receptor antagonists
(prevent substance P) these drugs are used mainly in cancer induced
chemotherapy
 NeuroKinin 1 antagonist →Aprepitant, Fosaprepitant

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