Abdominal Wall (1)
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Linea alba → runs from xiphoid process to pubic symphysis
Skin innervation →Lower 5 intercostal nerves (7-11), subcostal nerve, L1 spinal nerve (ilioinguinal + iliohypogastric
nn.)
Transpyloric plane: tip of 9th costal cartilages; pylorus of stomach, L1 vertebra level.
Subcostal plane: tip of 10th costal cartilages, L3 vertebra.
Transtubercular plane: tubercles of iliac crests; L5 vertebra level.
Interspinous plane: anterior superior iliac spines; L5 vertebra level.
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Semilunar line: lateral border of rectus abdominis
muscle.
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Flat abd. muscles continue as aponeuroses
anteromedially.
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External Oblique Muscle → O: 5-12th ribs; I: Linea alba +
pubic tubercle + iliac crest; N: lower 5 intercostal nn.+
subcostal n.
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inguinal ligament-reflected part of inguinal lig. (lig.
reflexum)- lacunar ligament.
pectineal lig.: lateral extension of lacunar lig.
Superficial inguinal ring: opening in the aponeurosis of external oblique m. has: lateral crus-medial crus- intercrural
fibres.
Internal Oblique Muscle → fibers right angle to those of ext. oblique m.
O: post.layerofthoracolumbarfascia+ iliac crest + lateral part of inguinal lig.; I: linea alba+conjoint tendon (common
tendon with the transversus abdominis m.) + pubic crest + pecten pubis; N: lower 5 intercostal nn. + subcostal n. +
small contribution from iliohypogastric & ilioinguinal nn.
Transversus abdominis muscle → O: inf.6 costal cartilages + thoracolumbar fascia + lateral part of inguinal ligament;
I: conjoint tendon + linea alba; N: lower 5 intercostal nn. + subcostal n. + small contribution from iliohypogastric &
ilioinguinal nn.
No trunk movement.
Rectus Abdominis Muscle → O: xiphoid process; I: symphysis pubis; enveloped by rectus sheath; N: lower 6
intercostal nn. + subcostal n.;flexes the trunk
• Pyramidalis Muscle → O: pubic bone and ant. surface of
pubic symphysis; I: linea alba; N: subcostal n.; F: streching
the lower part of linea alba
• Structures within the rectus sheath → rectus abdominis
m., sup. & inf. epigastric arteries, lower 5 intercostal nn.,
subcostal n., pyramidal m.
• (external oblique- turns the trunk to the other side);
internal oblique (turns the trunk to the same side).
Peritoneum and Inguinal Region (2)
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Median umbilical fold (urachus), Medial umbilical fold (umbilical arteries), lateral umbilical fold (inferior epigastric
vessels)
Btw median and medial folds: supravesical fossa, Btw medial and lateral folds: Medial inguinal fossa, Lateral to
lateral folds: lateral inguinal fossa
Ligamentum teres [round ligament] of liver → (obliterated umbilical vein)
Sites without peritoneum → Bare area of liver, Gastrophrenic lig., Transverse mesocolon, Root of mesentery,
Posterior to rectum, ascending and descending colons
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Proper mesentery (root) → From duodenojejunal junction on the left side of the L2 vertebra to the iliocolic junction
and right sacroiliac joint
Root of mesentery crosses → Horizontal part of duedonum, Abdominal aorta, Inferior vena cava, Right ureter, Right
psoas major, Right testicular or ovarian vessels
Between two layers of mesentery → Jejunum, Ileum, Jejunal and ileal branches of superior mesenteric vessels,
Autonomic nerves, Lymph nodes, Fatty tissue
Gastrolienal ligament → Left gastroomental artery, Short gastric arteries
Lienorenal ligament → Splenic artery and vein
Hepatogastric ligament Inside → Left and right gastric arteries
Hepatoduodenal ligament Inside → Proper hepatic artery, Common bile duct, Portal vein
Superior gastropancratic fold → Left gastric artery inside
Inferior gastropancreatic fold → Common hepatic artery inside
The parietal peritoneum lining the anterior abdominal wall is supplied by T6-T12 and L1.
In the region of diaphragm, the central part of the diaphragmatic peritoneum is innervated by phrenic nerves.
In the pelvic region, the parietal peritoneum is mainly supplied by the obturator nerve, which is a branch of the
lumbar plexus.
Lacunar ligament → Extends posteriorly to the pectineal line of pubis from the medial part of inguinal ligament
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Pectineal ligament → Extension of lacunar ligament laterally on the
pectineal line
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Reflected inguinal ligament → Medial fibers of inguinal ligament
extending to the linea alba
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Interfoveolar ligament → Extends to the superior ramus of pubis from
the inferior border of transversus; lateral to conjoint tendon; lateral to triangle
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Inguinal canal → Medially conjoint tendon thickens the posterior wall.
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Deep inguinal ring → Located lateral to interfovealar ligament and
inferior epigastric vessels.
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Inguinal canal structures → Spermatic cord, Ilıoinguinal nerve, Genital
branch of genitofemoral nerve, Round lig. of uterus
General Principles of Gastrointestinal Function (3)
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The digestive system performs four basic digestive processes: Motility, Secretion, Digestion, Absorption.
Mixing (segmentatiton) movements serve a twofold function → (1) by mixing food with the digestive juices, these
movements promote digestion of the food. (2) they facilitate absorption by exposing all parts of the intestinal
contents to the absorbing surfaces of the digestive tract.
In these regions motility involves skeletal muscle → Mouth at the beginning, External anal sphincter at the end
Normally, the digestive secretions are back into the blood after their participation in digestion.
From the innermost layer outward → the mucosa, the submucosa, the muscularis externa,and the serosa.
The lamina propria is a thin middle layer of connective tissue on which houses gut associated lymphoid tissue
(GALT).
Submucosal plexus lies within the submucosa.
Located throughout the layers of the muscularis externa are pacemaker cells known as the interstitial cells of Cajal.
o These pacemakers generate slow wave potentials. Slow wave potentials are not action potentials and do not
directly induce muscle contraction.
The digestive tract wall contains three types of sensory receptors → chemoreceptors, mechanoreceptors,
osmoreceptors
Digestion in the Mouth (4)
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The salivary NaCl (salt) concentration is only one seventh of that in the plasma, which is important in perceiving
salty tastes.
Similarly, discrimination of sweet tastes is enhanced by the absence of glucose in the saliva.
Saliva antibacterial action → lysozyme, binding glycoprotein (IgA), lactoferrin, rinsing away
Saliva is rich in bicarbonate buffers
The simple salivary reflex occurs when chemoreceptors and pressure receptors within the oral cavity respond to the
presence of food.
salivary center → located in the medulla of the brain stem
Conditioned, or acquired, salivary reflex → salivation occurs without oral stimulation.
Both sympathetic and parasympathetic stimulation increase salivary secretion, but the quantity, characteristics, and
mechanisms are different.
Parasympathetic stimulation → a prompt and abundant flow of watery saliva that is rich in enzymes.
Sympathetic stimulation → a much smaller volume of thick saliva that is rich in mucus
Once the bolus has entered the esophagus, the pharyngoesophageal sphincter closes, the respiratory airways are
opened, and breathing resumes → The oropharyngeal stage is completed, and about one second has passed since
the swallow was first initiated.
esophageal stage of the swallow → The swallowing center (via CNX) triggers a primary peristaltic wave that forces
the bolus ahead of it through the esophagus to the stomach.
The lodged bolus distends the esophagus, stimulating mechanoreceptors within its walls. In response to the
stimulus, the intrinsic nerve plexuses at the point of the distension initiates additional peristaltic waves.
o These secondary peristaltic waves do not involve the swallowing center, nor is the person aware of their
occurrence.
GES contraction also increases during inspiration.
After the bolus has entered the stomach, the swallow is complete and this lower esophageal sphincter again
contracts.
Esophageal secretion is entirely protective → mucus, lubricates the passage and protection
Digestion and Absorption of Carbohydrates, Proteins & Lipids (5)
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Dietary Fiber: Cannot be digested by human enzymes of intestinal tract. → lignan
The major dietary carbohydrate of animal origin is lactose
α-Amylase is endoglucosidase → hydrolyzes internal α-1,4 bonds between glucosyl residues at random intervals
The shortened chains called α-dextrins. α-Amylase is inactivated by stomach content (HCl).
Oligosaccharides called limit dextrins. They’re 4-9 glucosyl residues, contain one or more α-1,6 branches.
o α-amylase does not cleave these oligosaccharides all the way down to isomaltose.
α-amylase has no activity toward the α-1,6 bond at branching points and has little activity for α-1,4 bond at nonreducing end of the chain.
Dietary disaccharides (lactose and sucrose) are converted to monosaccharides by glycosidases (attached to
membrane in the brush-border of absorptive cells)
β-Glucoamylase → exoglucosidase, α-1,4, begins at non-reducing end, digests limit dextrin down to isomaltose
Sucrase-maltase site accounts for ~100% of the intestine’s ability to hydrolyze sucrose
Trehalase → Trehalose found in insects, algae, mushrooms, fungi
β-Glycosidase Complex (Lactase Glucosylceramidase) → The lactase catalytic site hydrolyzes the β-bond connecting
glucose and galactose.
o Other catalytic site hydrolyzes β-bond between Glucose and ceramide or Galactose and ceramide in glycolipids.
Duodenum → Production of maltose, maltotriose and limit dextrins by pancreatic α-amylase
Jejenum → Sucrase-isomaltase and β-glucosidase activities are highest.
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Ileum → Glucoamylase activity highest
Glucose is transported by → Na+ dependent transporters, Facilitative glucose transporters
Na+ dependent transporters → Located on the luminal side of absorptive cells, Low intracellular Na+ concentration
maintained by Na+-K+ ATPase.
Facilitative glucose transporters → do not bind Na+, present on serosal side of the cells.
o Glucose moves from high concentration inside the cell to the lower concentration in the blood without energy
expenditure.
Pepsin (at low pH), is not denatured, acts as an endopeptidase
Pepsin cleaves peptide bonds in which the carboxyl group is provided by an aromatic or acidic amino acids.
Intestinal epithelial → exopeptidases, Aminopeptidases (both on the brush border)
Amino acid abs → secondary active Na+ dependent transport systems and facilitated diffusion
Na-dependent carriers of the apical membrane of the intestinal epithelial cells are also present in the renal
epithelium.
The bile salts are amphipathic compounds (containing both hydrophobic and hydrophilic components)
Lingual and gastric lipases hydrolize short/medium chain fatty acids (< 12C)
Hydrolysis to fatty acids and 2-monoacylglycerols in intestinal lumen.
contraction of gallbladder and secretion of pancreatic enzymes by → cholecystokinin (CCK)
Bile salts act as detergents, emulsified fat has an increased surface area
Primary bile acids → Cholic acid, Chenodeoxycholic acid
Major enzyme digesting dietary TAG is pancreatic lipase.
o Secreted with → Colipase (prevents inhibitory effects of bile salts on lipase), HCO3HCO3- secretion is stimulated by Secretin
Fatty acids and 2-monoacylglycerols are packaged into micelles
Short and medium chain fatty acids (C4-C12) do not require bile salts for their absorption.
o Because they do not need to be packaged to increase their solubility, they enter the portal blood (rather than
the lymph) bound to serum albumin.
The bile salts are extensively resorbed when they reach the ileum.
Pathology of Oral Cavity (6)
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Aphthous Ulcers (Canker Sores) → covered with a thin exudate, erythematous rim
HSV infection → vesicles containing clear fluid, "cold sores", "fever blisters"
o focal edema: intraepithelial vesicles, intranuclear acidophilic viral inclusions (Tzanck test), polykaryons, herpetic
gingivostomatitis (child or immunocompromised)
Oral candidiasis (thrush, moniliasis) → immunocompromised, white, curdlike circumscribed plaque,
pseudomembrane can be scraped off (underlying granular erythematous inflammatory base)
Kaposi's sarcoma → in 20% of AIDS patients; intraoral purpuric discolorations or violaceous, raised, nodular masses
Hairy leukoplakia → only in HIV infection, "hairy" or hyperkeratotic thickening, caused by EBV inf.
Leukoplakia → white patch/plaque cannot be scraped off, hyperkeratosis, no other disease
o mild to severe dysplasia, carcinoma in situ; 5-25%: transformation to SCC
Erythroplasia → 90% marked epithelial dysplasia (malignant transformation rate is high!)
o Speckled leukoerythroplakia: intermediate form
SCC → advanced: ulcerated or protruding mass; spread to lymph nodes; moderately well-differentiated,
keratinizing
Sialadenitis → Mumps: paramyxovirus (mainly parotids), Mucocele: most common
Autoimmune sialadenitis → bilateral, seen in Sjögren's syndrome, all of SGs
o induces dry mouth (xerostomia) and dry eyes (keratoconjunctivitis sicca)
Bacterial sialadenitis → secondary to ductal obstruction, from stone formation (sialolithiasis)
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Pleomorphic Adenoma (Mixed Tumor of Salivary Glands) → most common (60%) tumor; mostly in
superficial parotid; painless swelling at angle of jaw; myxoid connective tissue stroma, sometimes islands
of chondroid or bone
Warthin's Tumor → 2nd common benign tumor, parotid gland, lymphoid tissue, germinal centers
Mucoepidermoid Carcinoma → most common malignant primary tumor and radiation induced neoplasm,
squamous, mucus-secreting and intermediate cells
Pathology of Esophagus (7)
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Paraesophageal hernias rarely induce reflux, but can become strangulated or obstructed
Achalasia → muscles of esophagus are inherently normal but derangement in innervation of LES
o risk of developing esophageal squamous cell carcinoma
Secondary achalasia → Chagas' disease, caused by Trypanosoma cruzi
primary achalasia → progressive dilation of the esophagus above LES
false diverticulum → mucosa and submucosa only; true → muscle too
Zenker diverticulum → immediately above UES, due to disordered cricopharyngeal motor dysfunction (in
older patients)
Traction diverticulum → near midpoint of esophagus, because of scarring resulting from mediastinal
lymphadenitis, like Tbc
Varices → cirrhosis
Lacerations (Mallory‐Weiss Syndrome) → mostly in chronic alcoholics after severe retching or vomiting
o Upper GI bleeding
Reflus esophagitis → eosinophils, with or without neutrophils; basal zone hyperplasia; elongation of
lamina propria papillae
Barrett’s esophagus → replacement of the normal distal stratified squamous mucosa by abnormal
metaplastic columnar epithelium containing goblet cells
o tongues extending up from GEJ, or isolated patches in the distal esophagus
o Most esophageal adenocarcinomas arise in the setting of Barrett’s esophagus/GERD
Eosinophilic Esophagitis → Esophageal rings, edema, narrowing, longitudinal furrow and white
dots/patches, mucosal fragility
o Lamina propria fibrosis is common
Lichen Planus → Civatte bodies (apoptotic bodies) similar to the cutaneous version
Pemphigus vulgaris (bullous) → Direct immunofluorescence for lgG and C3
Esophageal tumors → Most common is cancer (SCC [alcohol] and lesser adenocarcinomas [Barrett])
Histology of the Upper Digestive System (8)
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Oral cavity → stratified squamous keratinized and nonkeratinized epithelium
Masticatory mucosa → dorsal surface of the tongue, gingiva and hard palate, primary mucosa to be in
contact with food during mastication, keratinized to different degrees
Lining mucosa → 60% of total mucosa, covers the remaining surfaces of the oral cavity, nonkeratinized
stratified squamous epithelium (soft and pliable)
Specialized mucosa → 15%, covers dorsal tongue, keratinized epithelial papillae, taste buds
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Glands of von Ebner → located in the posterior aspect of the anterior one-third of the tongue and whose
ducts deliver their serous saliva into the epithelially lined groove of circumvallate papillae and the furrows
of the foliate papillae
Filliform Papilla → covered by stratified squamous keratinized epithelium, do not have taste buds
Fungiform Papilla → stratified squamous nonkeratinized epithelium, taste buds
Foliate Papilla → appear as vertical furrows; leaf like structure, taste buds
Circumvallate (Vallate) Papilla → appear as vertical furrows; walled papilla, have functional taste buds,
Von Ebner glands
Enamel → produced by ameloblasts
Dentin → type I collagen, produced by odontoblasts
Cementum → 45% to 50% calcium hydroxyapatite and 50% to 55% organic material, houses
cementocytes, produced by cementoblasts, type I collagen
The enamel develops from ectoderm of the oral cavity, all other tissues come from the associated
mesenchyme.
Esophagus → stratified squamous, usually non-keratinized epithelium
The lamina propria contain esophageal cardiac glands located in only two regions of the esophagus, one
group near the pharynx and the other near its junction with the stomach.
o It also has occasional lymphoid nodules, members of the gut- associated lymphoid system ( GALT ).
o The muscularis mucosae is unusual in that it consists of only a single layer of longitudinally oriented
smooth muscle fibers that become thicker in the vicinity of the stomach.
The esophageal cardiac glands produce a mucous secretion.
The esophagus and the duodenum are the only regions of the GIT with glands in the submucosa.
o They secrete proenzyme pepsinogen and the antibacterial agent lysozyme.
Adventitia covers the esophagus until it pierces the diaphragm, then is replaced by serosa.
Histology of the Lower Digestive System (9)
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Stomach → Gastric pits, three layers of smooth muscle,
o Acid producing cells (oxyntic or parietal cells), enzyme producing cells (chief or peptic cells)
o Enteroendocrine cells (APUD cells) - argentaffin cells
o Diffuse neuroendocrine cells (DNES) → Secrete gastrin, bombesin, VIP etc.
Gastric Mucosa → Superficial zone (Surface mucous cells, faveolae, pits, cripts), Neck zone (Stem cells,
neck mucous cells), Deep zone (Glands)
Chief and parietal cells → Most prominent in fundus region
Small intestine → intestinal glands (crypts of lieberkuhn) in the mucosa, blindly ended lymphatic channels
as lacteal
o Muscular Layer → inner circular layer, outer longitudinal layer, auerbach’s plexus between these
Cells of crypts of lieberkuhn → enterocytes, mucous cells (goblet cells), paneth cells (defensin), endocrine
cells, stem cells
Enterocytes and Goblet Cells take place both on surface epithelium and crypts of Lieberkühn
Paneth cells produce the bacteriocidal agent lyzozyme.
Duodenum → broader villi, less amount of goblet cells, Brunner’s glands in submucosa
Jejunum → villi are more longer and finger-like, goblet cells are increased in number, plica circulares, no
glands in the submucosa
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Ileum → Villi are shortest and narrowest, Clusters of lymphoıd tissue as Peyer’s Patches in mucosa and
submucosa, M cells (microfold cells), no glands in the submucosa
o M cells → Phagocytose antigens and transport them to the basal part of cells to be released into the
lamina propria to be presented to dentritic cells.
Large intestine → Columnar cells, Mucous cells (Goblet cells), Endocrine cells, Stem cells, crypts
Rectum and anal canal → Crypts of Lieberkühn are deeper and fewer, to the deeper region, Crypts of
Lieberkühn are totally erased
o Its mucosa represents longitudinal folds as Anal columns, they meet one another to make
outpocketings called as ANAL VALVES to support the column of feces
Anal mucosal epithelium is SIMPLE CUBOIDAL from rectum to pectinate line (at level of anal valves)
o Becomes STRATIFIED SQUAMOUS NONKERATINIZED from pectinate line to the external anal orifice
o Then STRATIFIED SQUAMOUS KERATINIZED at the anus
Anal glands at lamina propria of rectoanal junction
Anal canal → Submucosa contains two venous plexus (Internal hemorrhoidal plexus and External
hemorrhoidal plexus)
o Muscularis externa becomes thickened and makes internal anal sphincter muscle
o Skeletal muscles of the floor of the pelvis form an external anal sphincter muscle
Digestion in the Stomach (10)
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Body → thin smooth muscle, excorine secretion
Antrum → thick smooth muscle, excorine and edocrine secretion
Receptive relaxation (CNX) → When a meal is swallowed the smooth muscles in the fundus and body
relax before the arrival of food, allowing the stomach’s volume to increase.
o VIP, nitric oxide and serotonin released by enteric neurons mediate this relaxation.
Because the muscle layers are thin in the fundus and body, the peristaltic contractions in this region are
weak.
Gastric factors increase, duodenal factors decrease the rate of gastric emptying
The main gastric factor that influences the strength of contraction is the amount of chyme in the stomach.
The four most important duodenal factors that influence gastric emptying are fat, acid, hypertonicity, and
distension.
o The presence of one or more of these factors in the duodenum activates appropriate duodenal
receptors, triggering either a neural or a hormonal response
o The neural response is mediated through both the intrinsic nerve plexuses (short reflex) and the
autonomic nerves (long reflex). Collectively, these reflexes are called the enterogastric reflex.
Secretin and CCK inhibit antral contractions to reduce gastric emptying.
Fat is the most potent stimulus for inhibition of gastric motility.
The major force for vomiting comes from contraction of the respiratory muscles
Parietal (or oxyntic) cells secrete HCl and intrinsic factor.
Hydrogen ion (H+) and chloride ion (Cl-) are actively transported by separate pumps in the parietal cells’
plasma membrane.
H+ is derived from the breakdown of H2O molecules into H+ and OH within the parietal cells.
This H+ is secreted into the lumen by a H+–K+ ATPase pump in the parietal cell’s luminal membrane.
o The transported K + then passively leaks back into the lumen through luminal K + channels
The parietal cells contain an abundance of the enzyme carbonic anhydrase.
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o Driven by the HCO3- gradient, this carrier moves HCO3- out of the cell into the plasma down its
electrochemical gradient and simultaneously transports Cl- from the plasma into the parietal cell
against its electrochemical gradient.
Enterochromaffin-like (ECL) cells secrete paracrine histamine.
o Histamine acts locally on nearby parietal cells to speed up HCl secretion and potentiates the actions of
ACh and gastrin.
Protein in the stomach, the most potent stimulus, stimulates chemoreceptors that activate the intrinsic
nerve plexuses, which in turn stimulate the secretory cells.
The enterogastric reflex and the enterogastrones suppress the gastric secretory cells while they
simultaneously reduce the excitability of the gastric smooth muscle cells.
Luminal membranes of the gastric mucosal cells are almost impermeable to H, tight junctions.
Carbohydrate digestion continues under the influence of salivary amylase.
Digestion by the gastric juice itself is accomplished in the antrum of the stomach, where the food is
thoroughly mixed with HCl and pepsin, beginning protein digestion.
No food or water is absorbed into the blood through the stomach mucosa. (but ethyl alcohol and aspirin
are absorbed)
Histology of Liver (11)
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Glisson’s capsule
Hepatocytes bear microvilli on the apical surface
o Between two adjacent hepatocytes, bile canaliculi are located
The basolateral domain contains abundant microvilli and faces the space of Disse.
o The basolateral domain participates in the absorption of blood-borne substances and in the secretion
of plasma proteins
The apical domain borders the bile canaliculus, a trench-like depression lined by microvilli and sealed at
the sides by occluding junctions to prevent leakage of bile
Bile drainage → Bile canaliculus - Cholangioles (low cuboidal epithelium) - Canals of Hering - Interlobular
bile duct - Right and left hepatic ducts - Common hepatic duct unites with Cystic duct to form Common
bile duct - Common bile duct+pancreatic duct - Spincter of Oddi
Canal of Hering collects the bile from individual canaliculi and drain into the bile ductule
Each cholangiocyte possesses a long primary cilium, which sense changes in luminal flow of the bile.
Kupffer cells are phagocytic celse
Ito cells are for lipid storage
Pit cells are for natural killer activity
No complete basal lamina at the Space of Disse
This ovoid to diamond-shaped lobule is known as the hepatic acinus ( acinus of Rappaport ).
o The outermost layer, zone 3, extends as far as the central vein and is the most oxygen-poor of the
three zones. The remaining region is equally divided into two zones (1 and 2). Zone 1 is the richest in
oxygen and zone 2 has characteristics in between the other two zones.
Gall bladder → Mucosa is covered by TALL COLUMNAR EPITHELIUM, Numerous microvilli, Epithelial cells
are adapted for salt and water absorption, Numerous mucosal folds, No submucosa, Large number of
leukocytes
o External to muscularis externa, there is a thick layer of dense connective tissue (Tunica adventitia)
o Deep diverticula called ROKITANSKY-ASCHOFF SINUSES extend through the muscularis externa
Histology of the Pancreas and the Glands of the Digestive System (12)
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Pancreas → A thin layer of loose connective tissue form the CAPSULE
o Septa from the capsule form many lobules, a stroma of loose connective tissue surrounds the
parenchymal units
Pancreas exocrine → serous secretion, lobular structure, acini with centroacinar cells, no striated ducts
Centroacinar cells and the epithelial lining of the intercalated duct secrete HCO 3−, Na+, and water.
Cholecystokinin (CCK) stimulates enzyme secretion by the acinar cells. Secretin promotes water and HCO 3−
secretion by the duct cells.
Islets of Langerhans is richly vascularized, more islets in tail portion, each islet is surrounded by reticular
fibers
Capillaries first perfuse the A and D cells peripherilly before the blood reaches the B cells centrally.
Somatostatin is released in response to the increase levels of blood glucose or chylomicrons after a meal.
Insulin, vasoactive intestinal peptide (VIP) and Cholecystokinin (CCK) stimulate EXOCRINE FUNCTION.
Glucagon, pancreatic polypeptide and somatostatin inhibit EXOCRINE SECRETION.
Parotid pure serous, Submandibular gland mixed, Sublingual gland mixed
Salivary glands → Connective tissue septa divides the glands into lobules, myoepithelial cells surround the
acinar cells
Serous cell → Abundant secretory granules rich in ptyalin; single, round, basally located nucleus
Mucous cell → Pyramidal in shape, flattened nucleus
Intercalated ducts (low columnar or cuboidal) - Striated ducts (Tall columnar epithelium) - Interlobular
ducts (pseudostratified epith.) - Main duct of the gland (Ciliated epithelium)
Intercalated ducts → Carbonic anhydrase activity
Striated ducts → Reabsorption of sodium from primary secretion, addition of potassium to the secretion
As the duct approaches the oral epithelium, stratified squamous epithelium may be found
Motor and Secretory Functions of Small Intestine (13)
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Segmentation, the small intestine’s primary method of motility during digestion of a meal, both mixes and
slowly propels the chyme.
The circular smooth muscle’s degree of responsiveness and thus the intensity of segmentation
contractions can be influenced by distension of the intestine, by the hormone gastrin, and by extrinsic
nerve activity.
Segmentation is slight or absent between meals but becomes very vigorous immediately after a meal.
Both duodenum and ileum start to segment simultaneously when the meal first enters the small intestine.
Duodenum starts to segment primarily in response to local distension caused by the presence of chyme.
Segmentation of the empty ileum, in contrast, is brought about by gastrin secreted in response to the
presence of chyme in the stomach, a mechanism known as the gastroileal reflex.
The chyme slowly progresses forward because the frequency of segmentation declines along the length of
the small intestine.
When most of the meal has been absorbed, segmentation contractions cease and are replaced between
meals by the migrating motility complex, or “intestinal housekeeper.”
o This between-meal motility consists of weak, repetitive peristaltic waves that move a short distance
down the intestine before dying out.
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o These short peristaltic waves sweeps with each contraction any remnants of the preceding meal plus
mucosal debris and bacteria forward toward the colon.
The migrating motility complex is regulated between meals by the hormone motilin, which is secreted
during the unfed state by endocrine cells of the small-intestine mucosa.
When the next meal arrives, segmental activity is triggered again, and the migrating motility complex
ceases. Motilin release is inhibited by feeding.
Relaxation of the iliocecal sphincter is enhanced by the release of gastrin at the onset of a meal.
Each day the exocrine gland cells in the small-intestine mucosa secrete into the lumen about 1.5 liters of
an aqueous salt and mucus solution called succus entericus (“juice of intestine”).
o No digestive enzymes are secreted into this intestinal juice.
The small intestine does synthesize digestive enzymes, but they act within the brush-border membrane of
the epithelial cells that line the lumen instead of being secreted directly into the lumen.
Secretions of Exocrine Pancreas and Gall Bladder (14)
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Pancreatic enzymes actively secreted by the acinar cells that form the acini and an aqueous alkaline
solution actively secreted by the duct cells that line the pancreatic ducts.(rich in sodium bicarbonate
[NaHCO-])
The three major pancreatic proteolytic enzymes are trypsinogen,chymotrypsinogen,and
procarboxypeptidase, each of which is secreted in an inactive form.
o enterokinase (also known as enteropeptidase) activates trypsinogen
Enteropeptidase → an enzyme embedded in the luminal membrane of the cells of the duodenal mucosa.
Amylase and lipase are secreted in the pancreatic juice in an active form because they do not endanger
the secretory cells.
Pancreatic enzymes function best in a neutral or slightly alkaline environment
o This aqueous NaHCO - secretion is by far the largest component of pancreatic secretion.
In the presence of carbonic anhydrase, CO2 and H2O combine in the cells to + form H2CO3. H2CO3
dissociates into H and HCO3−.
The HCO3− is secreted into pancreatic juice by the Cl- - HCO3- exchanger in the apical membrane.
The H+ is transported into the blood by the Na + - H+ exchanger in the basolateral membrane.
Sodium diffuses through the “leaky” tight junctions into the lumen. Together these actions accomplish
NaHCO3- secretion.
The predominant stimulation of pancreatic secretion occurs during the intestinal phase of digestion when
chyme is in the small intestine.
o The release of the two major enterogastrones, secretin and cholecystokinin (CCK), in response to
chyme in the duodenum plays the central role in controlling pancreatic secretion.
The primary stimulus specifically for secretin release is acid in the duodenum.
o Secretin promotes the alkaline pancreatic secretion that neutralizes the acid. The amount of secretin
released is proportional to the amount of acid that enters the duodenum
Cholecystokinin is important in regulating pancreatic digestive enzyme secretion. The main stimulus for
release of CCK from the duodenal mucosa is the presence of fat and, to a lesser extent, protein products.
In contrast to fat and protein, carbohydrate does not have any direct influence on pancreatic digestive
enzyme secretion.
When chyme reaches the small intestine, CCK is secreted.
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o It stimulates contraction of the gallbladder and relaxation of the sphincter of Oddi, causing stored bile
to flow from the gallbladder into the lumen of the duodenum.
Most bile salts are reabsorbed into the blood by special active-transport mechanisms located in the
terminal ileum.
A bile salt molecule contains a lipid-soluble part (a steroid derived from cholesterol) plus a negatively
charged, water-soluble part → detergent action
The pancreas secretes the polypeptide coplipase along with lipase.
o Colipase binds at the surface of the fat droplets, where it binds to lipase, thus anchoring this enzyme
to its site of action among the bile salt coating.
Lecithin has both a lipid-soluble and a water-soluble part, whereas cholesterol is almost totally insoluble
in water. In a micelle, the bile salts and lecithin aggregate in small clusters with their fat-soluble parts
huddled together
In addition, cholesterol, a highly water-insoluble substance, dissolves in the micelle’s hydrophobic core.
This mechanism is important in cholesterol homeostasis.
Chemical mechanism (bile salts). Any substance that increases bile secretion by the liver is called a
choleretic. The most potent choleretic is bile salts themselves.
Hormonal mechanism (secretin). Besides increasing the aqueous NaHCO-3 secretion by the pancreas,
secretin stimulates an aqueous alkaline bile secretion by the liver ducts without any corresponding
increase in bile salts.
Neural mechanism (vagus nerve). Vagal stimulation of the liver plays a minor role in bile secretion during
the cephalic phase of digestion
Biochemical Aspects of Amino Acids and Protein Metabolism Disorders (15)
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PKU → Hyperphenylalaninemia; defects in phenylalanine hydroxylase, dihydrobiopterin reductase,
dihydrobiopterin biosynthesis
BH4 (tetrahydrobiopterin) is also required for tyrosine hydroxylase and tryptophan hydroxylase.
In PKU hydroxyphenylacetic acid and phenylacetic acid are thought to cause mental retardation.
Patients with phenylketonuria often show a deficiency of pigmentation.
o The hydroxylation of tyrosine by tyrosinase, which is the first step in the formation of the pigment
melanin, is competitively inhibited by the high
levels of phenylalanine present in PKU.
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The infant with PKU frequently has normal
blood levels of phenylalanine at birth because the
mother clears increased blood phenylalanine in
her affected fetus through the placenta.
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Albinism → a defect in tyrosine metabolism
results in a deficiency in the production of
melanin
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Complete albinism (also called tyrosinasenegative oculocutaneous albinism) → results
from a deficiency of copper-requiring tyrosinase,
a total absence of pigment from the hair, eyes,
and skin, increased risk for skin cancer
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Alkaptonuria → deficiency in homogentisic acid oxidase, accumulation of homogentisic acid
o homogentisic aciduria, large joint arthritis, black ochronotic pigmentation of cartilage
Maple syrup urine disease → defect involves the keto acid decarboxylase complex
o Plasma and urinary levels of leucine, isoleucine, valine, α-keto acids, and α-hydroxy acids (reduced αketo acids) are elevated.
o Prompt replacement of dietary protein by an amino acid mixture that lacks leucine, isoleucine, and
valine averts brain damage and early mortality.
Homocystinuria → high levels of homocysteine and methionine and low levels of cysteine; B12 coenzyme
Glutaric Acidemia Type I → an autosomal recessive disorder of lysine, hydroxylysine, and tryptophan
metabolsim caused by deficiency of glutaryl-CoA dehydrogenase
o Glutaric acid and 3-hydroxyglutaric acid accumulate especially in the urine
o This disorder can be identified by increased glutaryl carnitine on newborn screening.
Methylmalonic Acidemia → mutase is missing or deficient or unable to convert vitamin B12 into its
coenzyme form
Mass spectrometry is an analytical technique that measures the MASS-TO-CHARGE RATIO (m/z) OF IONS
Hyperammonemia → Hyperammonemia is a medical emergency, because ammonia has a direct
neurotoxic effect on the central nervous system.
o Liver disease (cirrhosis) is a common cause of hyperammonemia
o Congenital → Ornithine transcarbamoylase deficiency, which is X-linked, others AR
o Phenylbutyrate given orally is converted to phenylacetate. This condenses with glutamine to form
phenylacetylglutamine, which is excreted in the urine
Pathology of Gastritis and Peptic Ulcer (16)
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Acute gastritis → ranging from localized (NSAID) to diffuse inflammation of superficial or entire mucosal
thickness with hemorrhage and focal erosions (acute erosive hemorrhagic gastritis)
o mucosal edema, inflammatory infiltrate of neutrophils (activity), Erosion, hemorrhage
• Chronic gastritis → chronic mucosal inflammation
leading to atrophy and epithelial metaplasia, mildest
form is superficial gastritis
o Major entities → Helicobacter pylori gastritis,
autoimmune atrophic gastritis, Toxic, postsurgical
• Autoimmune gastritis → extensive multifocal
atrophy, autoantibodies to parietal cells, intrinsic
factor, acid‐producing enzyme H+K+‐ATPase
o gland destruction and mucosal atrophy + loss of
acid and Intrinsic factor (IF) production (pernicious
anemia), G-cell hyperplasia of the antral mucosa,
association with other autoimmune disorders
o intestinal metaplasia
o pathologic features of autoimmune and multifocal
atrophic gastritis are same, except, autoimmune
involves body and fundus, multifocal mainly antrum
o Hp‐induced proliferation of lymphoid tissue
Peptic ulcer damaging forces → gastric aciditiy, peptic enzymes
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o Defensive forces → Surface mucus secretion, Bicarbonate secretion into mucus, Mucosal blood flow,
Apical surface membrane transport, Epithelial regenerative capacity, Elaboration fo prostaglandins
Peptic ulcer → Hp enhance gastric acid secretion but decrease duodenal bicarbonate, pH ↓
o gastric metaplasia in duodenum: Hp colonization
o Increased IL-1, IL-6, IL-8, TNF by epithelial cell - PNL activation
o urease secretion by Hp generates free ammonia and monochloramine (toxic) and a protease that
breaks down glycoproteins in gastric mucus.
o Zollinger‐Ellison syndrome → multiple peptic ulcerations in stomach, duodenum, and even jejunum,
owing to excess gastrin secretion by a tumor and, excess gastric acid production
o Favored sites: anterior and posterior walls of first portion of duodenum and the lesser curvature of the
stomach, antral gastritis is most common
o surrounding mucosal folds radiate like wheel spokes, base of crater is clean
o if ulcer crater penetrates through the duodenal or gastric wall → a localized or generalized peritonitis
In a chronic, open ulcer, 4 zones → (1) necrotic fibrinoid debris (at base and margins) (2) active
nonspecific inflammatory infiltration (neutrophils predominating) (3) granulation tissue (4) fibrous,
collagenous scar
o Vessels trapped within the scarred area thickened and occasionally thrombosed
Acute peptic ulcers → Severe trauma, Extensive burns (Curling's ulcers), Traumatic or surgical injury to the
CNS or intracerebral hemorrhage (Cushing's ulcers), chronic exposure to gastric irritant drugs (NSAID–CS)
o anywhere in the stomach (Unlike chronic peptic ulcers)
Hypertrophic Gastropathy → a group of conditions all characterized by giant cerebriform enlargement of
the rugal folds
o Menetrier disease → hyperplasia of surface mucous cells with accompanying glandular atrophy,
severe loss of plasma proteins from the altered mucosa
o Hypertrophic-hypersecretory gastropathy → hyperplasia of the parietal and chief cells of glands
o Gastric gland hyperplasia → secondary to excessive gastrin secretion, in gastrinoma (Zollinger-Ellison
syndrome)
o the increase in acid secretion in the last two conditions increases the risk of peptic ulceration
o Infrequently they become metaplastic, a soil for the development of gastric carcinoma
Molecular Basis of Colon Cancer (17)
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MSI-H (high microsattellite instability) is the most common (about 70 %-95 %) caused by alteration of
hMLH1 gene via somatic promotor hypermethylation
Inherited mutations in the APC gene dramatically increase risk of colon cancer
WNT pathway → βcatenin mutations or loss of APC frees the β-catenin, it migrates to the nucleus and
activates aberrant gene expression
TGF-beta has a central role in inhibiting cell proliferation and serves as a tumor supressor
HNPCC (Lynch Syndrome) → AD, high penetrance; DNA mismatch repair (MMR) gene mutatitons; AOE 4050 years; Polyps may be present, multiple primaries common; The polyps have higher potential to turn
malignant (compared with FAP); Amsterdam II Criteria (3-2-1 rule); Microsatellite instability; hMLH1
deficiency; 60-70% right sided.
Familial adenomatous polyposis (FAP) → AD; descending colon and sigmoid; AOE adolescence through
adulthood; Multiple Primary cancers (several organs); Loss of APC results high levels of b catenin; Less
than 1% of the adenomas progress to carcinoma, but up to 2000 polyps increase the risk; No MMR
defects and MI.
Digestion and Absorption of the Small Intestine (18)
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Fat digestion is completed within the small-intestine lumen, but carbohydrate and protein digestion have
not been brought to completion.
Carbohydrate and protein digestion are completed within the confines of the brush border.
o Enterokinase (enteropeptidase), disaccharidases, aminopeptidases
Only the absorption of calcium and iron is adjusted to the body’s needs.
Most absorption occurs in the duodenum and jejunum; very little occurs in the ileum.
If the terminal ileum is removed, vitamin B12 and bile salts are not properly absorbed, because the
specialized transport mechanisms for these two substances are located only in this region.
Celiac disease (gluten enteropathy) → The exposure to gluten erroneously activates a T-cell response that
damages the intestinal villi.
The crypts of Lieberkühn secrete water and electrolytes, the crypts function as nurseries.
The new cells (derived from stem cells) undergo several changes as they migrate up the villus. The
concentration of brush-border enzymes increases and the capacity for absorption improves, so the cells at
the tip of the villus have the greatest digestive and absorptive capability.
Paneth cells serve a defensive function, safeguarding the stem cells. They produce two chemicals that
thwart bacteria: lysozyme, defensins
Sodium may be absorbed both passively and actively.
o secondary active transport via three different carriers: Na-Cl symporter, Na-H antiporter, or Naglucose (or amino acid) symporter.
▪ The absorption of Cl, H2O, glucose, and amino acids from the small intestine is linked to this
energy-dependent Na absorption.
Glucose and galactose are absorbed by Na+ and energy-dependent secondary active transport (via SGLT)
located at the luminal membrane.
o The operation of these symporters, which do not directly use energy themselves, depends on the Na+
concentration gradient established by the energy-consuming basolateral Na - K pump.
Fructose enters the cell by facilitated diffusion via GLUT-5.
Glucose, galactose, and fructose exit the cell at the basal membrane by passive facilitated diffusion via
GLUT-2.
About 20 to 40 g of endogenous protein enter the lumen each day from these three sources. This quantity
can amount to more than the quantity of protein in ingested food.
Amino acids are absorbed into the epithelial cells by means of Nat- and energy-dependent secondary
active transport via a symporter.
The amino-acid symporters are selective for different amino acids.
Some small peptides are absorbed by a different type of symporter driven by H+, Na*-, and energydependent tertiary active transport.
Bile salts are reabsorbed in the terminal ileum by special active transport.
The monoglycerides and free faty acids are resynthesized into triglycerides inside the epithelial cells.
Chylomicrons are unable ot cross the basement membrane of capillaries, so instead they enter the
lymphatic vessels, the central lacteals.
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The actual absorption or transfer of monoglycerides and free fatty acids from the chyme across the
luminal membrane of the small-intestinal epithelial cells is traditionally considered a passive process
o However, the overall sequence of events needed for fat absorption does require energy.
Vitamin B12 is unique in that it must be in combination with gastric intrinsic factor for absorption by
receptor-mediated endocytosis in the terminal ileum. Others passively.
Iron is actively transported from the lumen into the epithelial cells, with women having about four times
more active transport sites for iron than men.
Dietary Fe3+ (inorganic, plants) is reduced to Fe2+ by a membrane-bound enzyme at the luminal
membrane prior to absorption.
Vitamin C increases iron absorption, primarily by reducing Fe3+ to Fe2+. Phosphate and oxalate, in
contrast, combine with ingested iron to form insoluble iron salts that cannot be absorbed.
Heme iron enters the intestinal cell by heme carrier protein 1 and Fe2+ is carried in via divalent metal
transporter 1
Iron exits the small-intestine epithelial cell via a membrane iron transporter known as ferroportin. The
transport is aided by hephaestin.
Iron absorption is largely controlled hepcidin, which is released from the liver when iron levels in the body
become too high.
Iron stored as ferritin is lost in the feces within three days as the epithelial cells containing these granules
are sloughed off during mucosal regeneration.
Calcium enters the luminal membrane of the small-intestine epithelial cells down its electrochemical
gradient through a specialized Ca2+ channel, is ferried within the cell by a Ca2+ -binding protein,
calbindin, and exits the basolateral membrane by two energy-dependent mechanisms: a primary active
transport Ca2+ ATPase pump and a secondary active transport Na Ca2+ antiporter.
Biochemical Aspects of Carbohydrate Metabolism Disorders (19)
• Pyruvate kinase deficiency →
hemolytic anemia
• Glucose-6-Phosphatase in
liver (von Gierke’s disease) (I) →
Lactic acidosis
• Branching enzyme in organs
(liver) (Andersen’s disease) (IV)
→ Most severe disease,
abnormal glycogen, Failure to
thrive, Liver dysfunction
• Glycogen phosphorylase in
muscle (McArdle’s disease) (V)
→ Exercise indices muscle
cramps otherwise normal
• Pyruvate carboxylase
deficiency → lactic acidosis,
neurological dysfunction
(seizures, hypotonia, coma)
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PDH deficiency → assoc. with Leigh Syndrome
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G6PD deficiency → X-linked recessive, Most common enzyme-related hemolytic anemia, increased
resistance to falciparum malaria
o Oxidation of sulfhydryl groups of proteins inside RBCs causes protein denaturation and formation of
insoluble masses (Heinz bodies) that attach to RBCs membranes
G6PD deficient patients will develop hemolytic attacks upon → Intake of oxidant drugs (AAA), Exposure to
infection, Ingestion of fava beans
Galactosemia → cataract, liver damage, jaundice, diarrhea, severe mental retardation
Fructosuria → lack of fructokinase
Hereditary fructose intolerance (“Fructose poisoning”) → absence of aldolase B
Lactose-H2 breath test was positive because undigested lactose in the lumen of the gastrointestinal tract
was fermented by colonic bacteria.
Gastric, Intestinal, and Pancreatic Function Tests (20)
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Urinary/serum methylmalonic acid (MMA) → More sensitive and specific indicator of cobalamine
deficiency
Carcinoid syndrome, measure → Serotonin (5-hydroxytryptamine) (from Trytophan), 5-HIAA (serotonin
metabolite) (urine)
Persons with lactase deficiency exhibit abdominal discomfort and peak plasma glucose <100 mg/dl.
Ulcerative colitis → perinuclear antineutrophil cytoplasmic antibody (p-ANCA)
Crohn’s disease → antibodies to Saccharomyces cerevisiae
Once bound, the trypsin is not measurable using standard techniques, but any trypsinogen entering the
circulation can be measured as IRT (immune reactive trypsinogen) → Screening test for cystic fibrosis
Celiac Disease → Anti Gliadin Antibody IgA, Anti Gliadin Antibody IgG,Tissue transglutaminase Antibody
IgA, Tissue transglutaminase Antibody IgG
Motor and Secretory Functions and Abs in the Large Intestine; Defecation (21)
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The primary function of the large intestine is to store feces before defecation.
Cellulose and other indigestible substances in the diet provide bulk and help maintain regular bowel
movements by contributing to the volume of the colonic contents.
Segmentation contractions occur in the cecum and proximal colon. As in the small intestine, these
contractions function to mix the contents of the large intestine.
Mixing Movements—“Haustrations” → The haustra are not merely passive permanent gathers, however;
they actively change location as a result of contraction of the circular smooth muscle layer.
The colon’s main motility is haustral contractions initiated by the autonomous rhythmicity of colonic
smooth muscle cells. Much less frequently than small intestine.
Haustral contractions are largely controlled by locally mediated reflexes involving the intrinsic plexuses.
Propulsive movements- ‘Mass movements’ → Three to four times a day, generally after meals, a marked
increase in motility takes place during which large segments of the ascending and transverse colon
contract simultaneously, driving the feces one third to three fourths of the length of the colon in a few
seconds.
The appearance of mass movements after meals is facilitated by gastrocolic and duodenocolic reflexes
Gastrocolic reflex → mediated from the stomach to the colon by gastrin and extrinsic autonomic nerves.
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Duodenocolic reflex → triggered by a high tension in the duodenal wall, signal spreads through the
myenteric plexus
When defecation does occur, it is usually assisted by voluntary straining movements that involve
simultaneous contraction of the abdominal muscles and a forcible expiration against a closed glottis.
o This maneuver greatly increases intra-abdominal pressure, which helps expel the feces.
In usual infectious diarrhea, the infection is most extensive in large intestine and distal end of the ileum.
o Everywhere the infection is present, the mucosa becomes irritated, and its rate of secretion becomes
greatly enhanced.
o In addition, motility of the intestinal wall usually increases markedly.
Colonic secretion consists of an alkaline (NaHCO3-) mucus solution, whose function is to protect the largeintestine mucosa from mechanical and chemical injury.
Bacteria synthesize absorbable vitamin K and raise colonic acidity, thereby promoting the absorption of
calcium, magnesium, and zinc.
The colon normally absorbs salt and H2O. Sodium is actively absorbed, Cl follows passively down the
electrical gradient, and H2O follows osmotically.
Fecal material normally consists of 100 g of H2O and 50 g of solid, including undigested cellulose,
bilirubin, bacteria, and small amounts of salt.
Most gas in the colon is the result of bacterial activity, with the quantity and nature of the gas depending
on the type of food eaten and the characteristics of the colonic bacteria.
Tumors of the Upper and Lower Digestive Tract (22)
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Risk factors for SCC (esophagus) → Head and Neck Cancer, Tylosis, Thermal injury, radiation injury,
Plummer Vinson syndrome
Risk factors for ACA (esophagus) → Barrett, GER, obesity
Use of aspirin and NSAI drugs may reduce the ACA-SCC
ACA devolops in the distal E, whereas SCC may arise at any location in the E
EC tends to present advanced stage. Distant metastases occur %30 of patients, most commonly to the
liver, bone and lung
Most patients with EC don’t have symptoms until tumor is large enough to cause mechanical obstruction
Esophageal cancer remains highly fetal disease , the overall 5 –year survival rate is 13%
Gastric carcinoma metastases → Sister Joseph's nodule (umbilicus), Krukenberg's tumor (ovaries),
Virchow's node (Left Supraclavicular sentinel node), Rectal shelf of Blumer (Pouch of Douglass)
o Most common target organs: Liver (40%), lung, peritoneum, BM
o 5 year survival rate is less than 10% ( advanced Ca )
o Gastric Ca often presents with upper abd pain or iron deficiency anemia
The large majority of CRC are adenocarcinoma. Most commonly, cancers of the colon develop from
adenomatous polyps.
o Hyperplastic polyp is the most common polyp → tubular adenoma (65-80%)
o HNPCC is assoc with lower but significant risk of CRC.
o Right colon → no obstruction, more diarrhea; left colon → constipation
o Colon cancer is preventable.
o Rectal bleeding and a change in bowel habit are both strongly predictive of colorectal cancer and
inflammatory bowel disease
Biochemical Assessment of Liver Function (23)
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Aminotransferases are in low concentartions in the bile and cannot be identified in the urine. Urinary and
biliary clearance does not have a significant role.
AST and ALT → Both enzymes require pyridoxal-5’-phosphate (vitamin B6).
o This has clinical relevance in patients with alcoholic liver disease, in whom pyridoxal-5’-phosphate
deficiency may decrease ALT serum activity and contribute to the increase in the AST/ALT ratio that is
observed in these patients.
Mitochondrial AST release shows a more significant cell damage. ALT only in cytosol.
AST → Less specific for liver damage, cytosol and mitochondria of hepatocytes, AST can be elevated in
hemolysis, Cleared more rapidly than ALT
ALT → More specific for liver damage
AST/ALT ratio 0.8 in normal people
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AST grater than ALT in alcoholic hepatitis
and ratio grater than 2 suggestive of this disorder
(AST/ALT>2)
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Smaller increases in the ratio to values
grater than 1 occur in cirrhosis (AST/ALT
>1)Chronic
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CVH patients have an AST/ALT ratio below 1
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Isolated elevation of AST: Extrahepatic
origin of AST (muscle injury , muscle related
disease)
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AST-ALT levels may be normal in NAFLD,
hemochromatosis, HCV
Most common cause of mild elevated liver enzymes → Fatty liver disease
AP (Alk Phos) is an enzyme which transports cell membrane metabolite. The sources of AP are liver, bone,
placenta, kidneys, intestine
Methods:
o 1. Alk phos fractionation
o 2. GGT and 5’Nucleotidase can be used to confirm the liver origin of elevated ALP
Elevated GGT levels support a suspicion of alcohol abuse in a patients with elevated AST/ALT ratio of
grater than 2
Albumin Levels<3 mg/dL should raise the suspicion of chronic liver disease, not specific for liver.
PT (prothrombin time) → most important abnormality to signify development of fulminant hepatic failure
in course of acute liver disease
o Degree of elevation is a prognostic factor in many liver diseases
Bilirubin → Reflects the capacity of the liver to transport organic anions and to metabolize drugs.
Peptic Ulcer Disease (24)
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Etiology → H. pylori, NSAIDs, critical illnes (stress ulcers)
o Stess ulcers are not due to psychologic disturbances
Antral infection → Gastrin increases, Acid secretion increases, pH decreases, Assoc with duodenal ulcer
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Corporal infection, Atrophy of antral mucosa → gastrin decreases, acid sec decreases, assoc w/ gastric
ulcer and cancer
HPI diagnosis → Serology (!) (IgG), Stool antigen test, Urea breath tests, Endoscopy and biopsy
Epigastric pain:
o Gastric PUD → Associated with hunger, decreases with food
o Duodenal PUD → Decreases with food but may increase hours after meals
Indications for endoscopy → Age > 50 with new onset of symptoms, Glascow-Blatchford score, Alarm
syptoms
Stop offending medications such as NSAIDs, ASA, bisphosphonates etc.
Do not stop anti-platalet drugs in high-risk cardiovascular disease patients
The patient passes a stool that is dark and tarry, and a guiacc test is positive for occult blood. → NSAID
caused PUD
Neoplastic diseases of the stomach (25)
SLAYT
Tumors of small and large intestine (26)
SLAYT
Regulation of feeding (27)
SLAYT
Drugs for the therapy of acid peptic diseases (28)
SLAYT
Development of digestive system (29)
SLAYT