Gastrointestinal A&P
 Function:
 Mechanical & chemical breakdown of food
 Absorption of nutrients
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GI tract:
 Hollow tube from mouth to anus
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Mouth:
 Breakdown begins w/chewing + salivation (α-amylase→CHO digestion)
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Esophagus:
 Transports bolus via swallowing
 Oropharyngeal (voluntary)
 Esophageal (involuntary)
 Lower esophageal sphincter (opens to allow food into stomach; closes to prevent regurgitation into esophagus)
 Stomach:
 Secretes digestive juices + HCL + pepsin
 Mixes/stores food; propels chyme into duodenum via peristalsis
 Gastrointestinal A&P
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Small intestine: (5 meters long!)
 Duodenum→Receives chyme through pyloric sphincter→bile (fats) + pancreatic enzymes (proteins, CHOs, fats) +
intestinal enzymes (proteins, CHOs, fats)
 Jejunum→Sugars & proteins absorbed
 Ileum→Bile salts, Vit B12, chloride absorbed
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Large intestine: (“leftovers” enter via ileocecal valve)
 Cecum, appendix, colon (ascending, transverse, descending, sigmoid), rectum
When Things Go Wrong—GI Disorders
 Motility disorders
 Gastritis
 Peptic ulcer disease
 Malabsorption syndromes
 Inflammatory bowel disease
 Appendicitis
 Vascular insufficiency
 Disorders of nutrition
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Motility Disorders
A)Dysphagia
 Difficulty swallowing
 Causes:
 Mechanical obstruction of esophagus (tumors inside or outside, strictures, diverticular herniations)
 Impairment of esophageal motility (CVA, Parkinson disease, achalasia)
 Achalasia: nerve dysfunction→failure of muscular ring at end of esophagus to relax→lower esophagus becomes
distended
 In a condition called achalasia, the lower esophageal sphincter fails to relax; food that has been
swallowed has difficulty passing into the stomach, and the esophagus above the lower esophageal
sphincter becomes enlarged. One or several meals may lodge in the esophagus and pass slowly into the
stomach over time. There is danger of aspiration of esophageal contents into the lungs when the
person lies down
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B) Gastroesophageal Reflux
Reflux of chyme into esophagus from the stomach
Common symptom: “Heartburn”
If long term→esophageal inflammation & erosion→fibrosis & thickening
Causes: Obesity, smoking, delayed gastric emptying (ulcers, pyloric stricture, hiatal hernia)
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C) Hiatal Hernia
Potrusion of ↑ stomach thru diaphragm
Sliding (congenital, short esophagus, trauma, weak diaphragm muscles)
 S/S: GER, esophagitis
Paraesophageal(curvature of stomach herniates alongside of esophagus)
 S/S: Discomfort after eating, dysphagia
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D) Pyloric Obstruction
Narrowing / blocking of pyloric sphincter
Congenital
Acquired (PUD, carcinoma of pylorus)
S/S: (early) vague epigastric fullness—worse after meals & late in day; nausea; epigastric pain
S/S: (late) gastric distention; vomiting; infrequent, small stools
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E) Intestinal Obstruction
Simple: mechanical blockage
 Acute: Torsion, intussusception, herniation
 Chronic: Tumor, inflammatory disorder
Functional: ↓ motility (Ex—paralytic ileus)
S/S: “Colicky” pain + vomiting
May become necrotic, perforate → peritonitis (infection)
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2) Gastritis
 Inflammation of gastric mucosa
 Acute: Erosions usually superficial. Acute gastritis refers to a transient inflammation of the gastric mucosa. It’s most
commonly associated with local irritants such as bacterial endotoxins, alcohol, and aspirin.
 Cause: Chemicals, drugs (NSAIDS)
 S/S: Vague abdominal discomfort; epigastric tenderness; BLEEDING (bleeding and hematemesis are associated
with alcohol consumption, vauge s/s associated with NSAID use)
 Chronic: Age=thinning/degeneration of stomach wall=loss of chief & parietal cells→ ↓ acid→ ↑ gastrin in plasma→
pernicious anemia (↓Vit. B12 absorbed). It’s characterized by the absence of grossly visible erosions and the presence of
chronic inflammatory changes leading eventually to atrophy of the glandular epithelium of the stomach.
 Cause: ?Autoimmune, H. pylori
3) Peptic Ulcer Disease
 Break / ulceration in protective mucosal lining of stomach, duodenum
 Submucosa exposed to gastric secretions → autodigestion
 ↑ Risk: Smoking, ↑ age, NSAIDS, alcohol, H. pylori, chronic diseases
• Gastric/Duodenal Ulcers
 Causes:
 NSAIDS→ inhibits prostaglandins + ↓mucus production
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 H. pylori→ stimulates gastrin production→ ↑acid production/ulcer formation
S/S: Chronic intermittent pain relieved by food intake/antacid use; 1 st clinical manifestation may be hemorrhage /
perforation
4) Malabsorption Syndromes
 Interfere with nutrient absorption in small intestine
 Pancreatic insufficiency→ Deficient production of pancreatic enzymes (affects digestion of proteins, CHO, fats)
 Lactase deficiency→ Lactose not broken down
 Bile salt deficiency→ Fats not digested / absorbed
5) Inflammatory Bowel Disease
 Ulcerative colitis—chronic, inflammatory→ulceration of mucosa in colon (usually in sigmoid & rectum)
 Crohn disease—inflammatory, affects both small & large intestine (rectum is seldom involved)
 Diverticular disease—herniations / saclike outpouchings of mucosa thru muscle layers (usually wall of sigmoid colon)
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6) Appendicitis
 Inflammation of vermiform appendix
 Most common surgical emergency of abdomen
 Generally 20-30 years of age (can happen at any age
 Cause: ?obstruction of lumen w/stool, foreign bodies, tumors → bacterial infection
 Obstruction → appendix can’t drain → ↑pressure → appendix becomes hypoxic → mucosa ulcerates → bacteria invasion
→ inflammation → gangrene → perforation
7) Vascular Insufficiency
 Gastrointestinal system extremely vascular
 Atherosclerotic lesions, emboli, thrombi can occlude blood flow anywhere
 Chronic mesentary insufficiency can develop as result of cardiovascular disorders—cardinal s/s: Colicky abdominal pain
after eating
8) Disorders of Nutrition
 Obesity
 Complex disorder
 Numerous theories
 Increases risk for CAD, DM, gallstones, HTN, CVD; breast/cervical/endometrial/ liver CA in women;
prostate/colon/rectal CA in men
 Anorexia nervosa / bulimia nervosa
 Psychologic syndromes
 Starvation—short-term vs long-term
Liver, GB, Pancreas A&P Review
• Contribute enzymes, bile, hormones
• All three organs vital to digestion
• Deliver secretions to the duodenum through duct system
Liver Structure
• Large
• Highly Vascular
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Enclosed in upper right abdomen
Liver has blood supply from the heart and from the GI tract. GI tract blood supply provides the nutrients and low
oxygenated blood
Glisson capsule covers liver (blood vessels, lymphatics, nerves) When the liver is diseased or swollen, distention of the
capsule causes pain et the lymphatics may ooze fluid into the peritoneal space
Hepatic artery (oxygenated blood)from the heart
Portal vein (some oxygen + nutrients)from the GI tract
Liver lobules – smaller anatomic units
Metabolic functions of the liver require a large amount of blood. The liver receives blood from both arterial and venous
sources. The hepatic artery branches from the abdominal aorta and provides oxygenated blood (400-500ml/min). The
hepatic portal vein, which receives blood from the inferior and superior mesenteric veins and the splenic vein, delivers
about 1000-1200ml/min to the liver. Portal venous blood constitutes 70% of the blood supply to the liver. This blood
carries some oxygen and is rich in nutrients that have been absorbed from the digestive tract.
Hepatocytes “plates” (functional cells of liver) – can regenerate, therefore damaged or resected liver tissue can regrow
Sinusoids (capillaries between plates of hepatocytes) – located between the plates of hepatocytes, receive mixture of
arterial and venous blood from branches of the hepatic artery and portal vein. Blood from the sinusoids drains to a
central vein in the middle of each lobule. Venous blood from all the lobules then flows into the hepatic vein, which
empties into the IVC
Kupffer cells (mononuclear phagocyte system) immunity cells
The sinusoids of the liver lobules are lined with highly permeable endothelium. This permeability
enhances the transport of nutrients from the sinusoids into the hepatocytes, where they are
metabolized. The sinusoids are also lined with phagocytic Kupffer cells, which are part of the
mononuclear phagocyte system.
These Kupffer cells remove foreign substances from the blood and trap bacteria.
• Disse space (hepatic lymph system) drainage Between the endothelial lining of the sinusoid and the hepatocyte is the
Disse space, which drains interstitial fluid into the hepatic lymph system.
• Bile canaliculi (channels that conduct bile to bile ducts)
• Common bile duct >Sphincter of Oddi
Liver Function
• Performs numerous complex & important functions
• Many related to digestion & nutrition
A large, highly vascular organ, the liver is enclosed in a fibrous capsule in the upper right area of the abd. The liver performs
numerous complex and important functions, many of which are related to digestion and nutrition
Liver Function #1
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Filters/detoxifies blood
– Metabolic detoxification / biotransformation (cuts down reabsorption of potentially toxic substances, then
facilitates their excretions through the intestines or kidneys
– Alchohol, barbiturates, amphetamines, steroids and hormones (estrogens, aldosterone, ADH, testosterone) are
metabolized, preventing excessive accumulation and AE
– Alters chemicals to make less toxic, or biologically active
– *****However, sometimes the end products of this process themselves can become toxins. For example, end
products of alcohol metabolism are acetaldehyde and hydrogen. Excessive alcohol intake over a prolonged
period causes these end products to damage hepatocytes. Acetaldehyde (poison) damages cellular
mitochondria, and the excess hydrogen promotes fat accumulation. This is how alcohol impairs the liver’s
ability to function.
– Diminishes intestinal reabsorption
– Diminishes renal tubular reabsorption
Liver Function #2
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Removes ammonia from body fluids
– Process called deamination (amino acids converted to carbohydrates, or ketoacids, by removal of ammonia)
– Converts to urea, then passes into the blood
– Excreted in urine
Liver Function #3
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Produces bile
– Contains bile salts, bilirubin, etc.
– Emulsifies fats
– Helps in absorption of fats
The liver secretes 700 to 1200 ml of bile per day. Bile contains bile salts, cholesterol, bilirubin, electrolytes, water.
It is formed by hepatocytes & secreted into the canaliculi. Bile salts (conjugated bile acids), are needed for emulsifying
and absorption of fats. After this work is done, most bile salts are actively absorbed in the terminal ileum and returned
to the liver through the portal circulation for resecretion.
This recycling of bile salts is called the enterohepatic circulation.
Conjugation, or binding of bile acids with amino acids, makes the bile acids more water soluble, thus keeping them from
being diffused in the duodenum & ileum.
Intestinal bacteria will deconjugate some bile salts back into bile acids (secondary bile acids). These acids diffuse
passively into the portal blood from both small & large intestines. An increase in the plasma concentration of bile acids
accelerates the uptake and resecretion of bile acids and salts by the hepatocytes. The cycle of hepatic secretion,
intestinal absorption, and hepatic resecretion of bile acids completes the enterohepatic circulation.
Bile secretion is called choleresis. A choleretic agent stimulates the liver to secrete bile. One strong stimulus is a high
concentration of bile salts. Other choleretics include secretin, which increases the rate of bile flow by promoting the
secretion of bicarbonate from canaliculi and other intrahepatic bile ducts; cholecystokinin; and vagal stimulation.
– See Figure 29-4, p. 636 in Porth
Liver Function #4
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Produces plasma proteins
– Albumins and globulins (synthesized by liver)
– Maintains blood volume & pressure
Synthesizes nonessential amino acids (tested with liver function test)
– AST, ALT, LDH, alkaline phosphatase
Can store vitamin A for several years
Liver Function #5
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Plays important role in carbohydrate metabolism
– Releases glucose during hypoglycemia
– Takes up glucose during hyperglycemia
The liver MANAGES (contributes to the stability of blood glucouse leves by releasing glucose during times of low blood sugar and
taking up glucose during time of high blood sugar
Liver Function #6
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Converts glucose to glycogen
• Glyconeogenesis
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Stores it for fuel for muscles
Or, converts glucose to fat
Can convert amino acids & glycerol to glucose
• Gluconeogenesis
Liver Function #7
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Stores essential nutrients
• Iron (as ferritin) & copper – released as needed for red blood cell production
• Vitamin B12 & D—stores for several months
• Vitamin A – stores for several years
• Vitamins E & K
• The liver stores these and in times of excessive intake and releases them in times of need
Liver Function #8
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Stores fats – synthesized from carbs and protein
• Fat absorbed by lacteals in the intestinal villi enter the liver through the lympatics, primarily as triglycerides.
Triglycerides can be hydrolyzed to glycerol and free fatty acids and used to produce ATP (for cellular use)
Converts excess sugars to fats – Stored in adipose tissue
Liver Functions #9, #10, #11
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Storage of large volumes of blood
Removal of bacteria & foreign particles
Synthesizes prothrombin, fibrinogen, factors I, II, VII, IX, X
Because of its extensive vascular network, the liver can store a large volume of blood. The amount stored at any one
time depends on pressure relationships in the arteries and veins. The liver also can release blood to maintain systemic
circulatory volume in the event of hemorrhage.
Kupffer cells in the sinusoids of the liver remove bacteria and foreign particles from the portal blood. Because the liver
receives all the venous blood from the gut and pancreas, the Kupffer cells play an important role in destroying intestinal
bacteria and preventing infections.
The liver also has hemostatic functions. It synthesizes prothrombin, fibrinogen, and factors I, II, VII, IX, and X, all of which
are necessary for effective clotting. Vitamin K, a fat-soluble vitamin, is essential for the synthesis of other clotting
factors. Because bile salts are needed for reabsorption of fats, vitamin K absorption depends on adequate bile
production in the liver.
Liver Function #12
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Metabolism of bilirubin
• By-product of destruction of old rbc’s
• Gives bile greenish black color
• Produces yellow tinge of jaundice
See Handouts re: Enterohepatic circulation of bile salts & Bilirubin Metabolism
Liver Disorders
• Viral hepatitis
• Fulminant hepatitis
• Alcoholic cirrhosis
• Biliary cirrhosis
Viral hepatitis
• Relatively common
• Affects primarily the liver
• All five types (A, B, C, D, E) can cause acute, icteric (jaundice) illness
• Pathologic lesions similar to other viral infections (“you’ve seen one…”)
• Hepatic cell necrosis
• Kupffer cell hyperplasia
• Infiltration by mononuclear phagocytes (varying severity)
• An inflammatory process
• Can damage/obstruct bile canaliculi
• Leads to cholestasis & obstructive jaundice
• In milder cases, liver parenchyma (functional tissue) not damaged
• Damage tends to be most severe in Hep B & Hep C
• Hep B can result in acute fulminating hepatitis
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Wide spectrum of manifestations
• Absence of symptoms→fulminating hepatitis with liver failure & coma
• Causes abnormal liver function test results: ↑serum aminotransferase, ↑AST, ↑ALT
• AST = aspartate transaminase
• ALT = alanine transaminase
Clinical course:
• Prodromal phase—begins @ 2 weeks post exposure; ends w/appearance of jaundice
• Clinical (Icteric) phase—begins 1-2 weeks after prodromal phase; lasts 2-6 weeks
• Recovery phase—begins w/resolution of jaundice, @ 6-8 weeks post exposure
Viral hepatitis—Clinical Manifestations
Prodromal phase:
• Appearance of jaundice
• Fatigue / malaise (caused by systemic effects of liver inflammation)
• Anorexia (caused by systemic effects of liver inflammation on the GI system)
• Nausea/vomiting
• Arthralgia / Myalgia
• Headache
• Changes in sense of taste and smell
• Hyperalgia (extreme sensitivity to pain)
• Cough
• Low-grade fever
Clinical phase: (actual phase of illnesss)
– Worsening of all symptoms of the prodromal stage
• Jaundice
• Itching
• Dark urine
• Clay-colored stools
• Enlarged, smooth liver
• Liver tender, painful to percussion
Recovery phase:
• Begins w/resolution of jaundice
• Symptoms diminish
• Liver remains enlarged/tender
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Liver function returns to normal
Viral hepatitis--Complications
• Chronic active hepatitis (if it happens at least twice)
• Cirrhosis
• Hepatic failure & death
• Primary hepatocellular carcinoma
Fulminant hepatitis
• Clinical syndrome
• Results in severe liver impairment / necrosis of liver cells
• High potential for liver failure
• May occur as complication of:
• HCV infection
• HBV infection
• Combination HBV / HDV infection
• Rarely occurs with HAV infections
• May also occur as a result of:
• Toxic reactions to drugs (eg. Tylenol)
• Congenital metabolic disorders
Clinical course:
• Develops 6-8 weeks post initial symptoms
• Many of same symptoms + ascites & GI bleed
• Hepatic encephalopathy
• Hepatic necrosis irreversible, 60% to 90% die
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Acute liver failure usually develops within 6-8 weeks after the initial symptoms of viral hepatitis or a metabolic liver
disorder. Anorexia, vomiting abdominal pain, & progressive jaundice are initial signs, followed by ascites & GI bleed.
Hepatic encephalopathy is manifested as lethargy, altered motor functions, and coma & is related to cerebral edema,
ischemia, & brain stem herniation. Liver function tests show elevations of both direct & indirect serum bilirubin, serum
transaminases, & blood ammonia. Prothrombin time (PT) is prolonged. Renal failure & pulmonary distress can occur.
Antiviral reverse transcriptase inhibitors are available to treat chronic hepatitis B or C. Treatment of acute liver failure is
supportive. The hepatic necrosis is irreversible, & 60% to 90% of affected children die. Liver transplantation may be
lifesaving & should be considered early.
It’s amazing, but survivors usually do not develop cirrhosis or chronic liver disease.
Cirrhosis
• Chronic liver disease—develops slowly
• Widespread destruction of hepatic cells + collapse of supporting structure
• Replaced by fibrous cells
• Liver develops “cobbly” appearance
• Cirrhosis is a chronic liver disease. It’s characterized by widespread destruction of hepatic cells, which are replaced by
fibrous cells. This process is called fibrotic regeneration. Cirrhosis is a common cause of death in the U.S. It’s twice as
common in men as in women, and is especially prevalent among malnourished persons over age 50 with chronic
alcoholism. Mortality is high; many patients die within 5 years of onset.
• IT’S INTERESTING TO ME THAT DEATHS FROM ALCOHOL-RELATED LIVER DISEASE HAVE INCREASED OVER THE LAST
DECADE. HOWEVER, HIGH ALCOHOL CONSUMPTION AMONG WOMEN LEADS TO EARLIER & MORE SEVERE CIRRHOSIS.
ALTHOUGH ALCOHOLIC CIRRHOSIS IS THE MOST PREVALENT OF THE DIFFERENT TYPES OF CIRRHOSIS, THE OCCURRENCE
OF CIRRHOSIS AMONG PERSONS WITH ALCOHOLISM IS RELATIVELY LOW (@25%).
Cirrhosis--Types
• Classified by “cause” (See Handout of Cirrhosis of the liver)
• Most common:
• Laennec’s (also called alcoholic, portal, fatty cirrhosis)
• Postnecrotic
• Biliary
• Metabolic
Alcoholic (Laennec’s) cirrhosis
• Alcohol transformed into acetaldehyde
• Excessive acetaldehyde:
• ↓hepatocyte function
• ↓oxidation of fatty acids
• ↓enzyme/protein synthesis
• ↓ammonia breakdown
• ↓proteins leaving liver (albumin…)
• ↓metabolism of vitamins/minerals (malnutrition)
• Damage to hepatocytes leads to:
• Inflammatory response
• Results in excessive collagen formation
• Fibrosis/scarring alter liver structure
• Leads to bile canaliculi/duct obstruction
• As well as sinusoid (capillary) obstruction
• Alcoholic cirrhosis (Cont’d)
• Begins with fatty liver
• ↑Lipogenesis
• ↓Fatty acid oxidation
• Possible mobilization of lipids from adipose tissue
• Fatty accumulation reversible w/cessation of alcohol consumption
• Fibrosis/liver damage irreversible
Alcoholic cirrhosis—symptoms
• Enlarged liver (initially—fatty infiltration
• Many of same s/s of hepatitis (fatigue, anorexia, nausea, etc)
• Later s/s—ascites, esophageal varices, testicular atrophy, splenomegaly
• Postnecrotic cirrhosis
• Develops from chronic hepatitis
• Exposure to arsenic, carbon tetrachloride, other toxins
• More common in women
• Most common type worldwide
• Biliary cirrhosis (primary)
• Damage begins in bile canaliculi / bile ducts (inflammation, then destruction)
• Primary—idiopathic (we don’t know why)
• Pruritis/hyperbilirubinemia/jaundice→light-colored stools → cirrhosis → portal hypertension→encephalopathy
• Biliary cirrhosis (primary)
• Affect women & those > 30 years old. Life expectancy is 5-10 years after onset of symptoms.
• Disease specific antibodies can be detected—
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Antiretroviral treatment is being tried—
Liver transplant is very effective–
Biliary cirrhosis (Secondary)
• Prolonged obstruction of bile duct branches / common bile duct
• Secondary biliary cirrhosis can be caught and managed by endoscopic removal of stones/stent placement, or by surgery
• Gallstones
• Tumors
• Chronic pancreatitis
• Fibrotic stricture
• Cystic fibrosis (children)
• Biliary atresia (children)
Metabolic cirrhosis
Metabolic diseases can lead to cirrhosis:
• Wilson’s disease (copper not being excreted in the bile)
• Alpha¹-antitrypsin (hereditary disease, not putting out alpha1 antitrypsin)
• Hemochromatosis (iron overload)
Portal Hypertension
• Cause: Any disorder that slows (impedes) or blocks (obstructs) blood flow through any part of portal venous system
• Can result from:
– Inflammation (hepatitis, etc.)
– Fibrosis of sinusoids (cirrhosis)
– Thrombosis (blood clots)
• Long-term portal hypertension causes:
– Ascites
– Varices (esophageal, gastric, rectal)
– Splenomegaly
– Hepatic encephalopathy