Cirhosis etiologies
- EtOH abuse
15% of heavy drinkers
- Viral
- Prolonged cholestasis - primary cirrhosis, primary sclerosing cholangitis,
- Metabolic - hemochromotosis, wilson disease, alpha 1 antitrypsin deficiency
- Congestive -
- Non-alcoholic steatohepatitis (NASH) - now single most common cause of liver failure
Pathophysiology
- Increased portal venous resistance
Hepatocellular injury --> fibrosis, nodularity --> flow resistance
- Increased portal venous inflow
Increased glucagon --> splanchinic hyperemia
GI sensitivity, catecholamines --> splanchnic hyperemia
Extrahepatic, intrahepatic,
Two primary problems develop
- Hepatocellular failure
- Portal hypertension
6th leading cause of death in 35-54 year olds
- Fulminant liver failure
- Variceal hemorrhage
Classification
- Child-Pugh Score
Total bilirubin, serum albumin, PT or INR, Ascites (completely controlled, partially controlled or uncontrolled), presence of encephalopathy (abscent, mild, severe)
Child A, B or C
Used for assessment for surgical risk, also predictive of survival
Operative mortality for major abd surgery - A: 10%, B: 17-31%, C: 63-82%
- MELD score
Surface Anatomy
- As high as the 5th rib on the right and 6th on the left
- Avoid the trans-hepatic chest tube
Gross Anatomy
- Falciform ligament traditional defined left from right, no functional significance
Embryology
- Develops with the biliary tree and pancreas
- Begins as an endodermal epithelial out pouching
- Hepatic diverticulum - the opening narrows forming bile duct
- Ligamentum teres – inferior edge of falciform, remnant of umbilical vein from umbilicus to the umbilical fissure of liver
- Viteline veins become portal system
- Important role in hematopoiesis - Main site between months 2 and 7 of gestation
Functional anatomy
Cantile’s line - imaginary line from IVC to fundus of gallbladder, demarcates r and left
Couinaud segments
- Each segment fed by own portal pedicle (=triad of portal vein, hepatic artery, bile duct)
- Left: Segments 2, 3, 4a, 4b
- Right: Segments 5, 6, 7, 8
- Caudate lobe (segment 1): Fed by both right and left pedicles, surrounds IVC
Portal Vein
- Forms from superior mesenteric and splenic veins, inferior mesenteric joins splenic
- 75% of blood flow to liver
- provides 50-70% of oxygenation to liver
- Low pressure, high flow
- Usual pressure <5mm Hg
- If greater than 10 = significant portal HTN
- See other lecture regarding portal HTN
Hepatic Artery
- Celiac trunk gives off common hepatic, left gastric and splenic
- Common hepatic gives off gastroduodenal, supraduodenal and right gastric then forms the proper hepatic
- Proper hepatic gives branches into right, left, middle and cystic
- 25% blood flow to liver
- 30-50% of oxygen
- Typical anatomy only present 60% of the time
- Most common is replaced right hepatic (11-21% of variations) from the SMA
- Replaced left is 3.8-10% of the time
Biliary Anatomy
- Left and Right hepatic ducts drain their respective liver segments
- Caudate has its own drainage usually through both right and left systems
- In 15% it is only through the left, 5% only through the right
- CBD is 10-15cm long; 6mm in diameter
- GB lies against segments 4 and 5
- There are variations of the GB and biliary tree
- Variations in the cystic artery
- Variation in gallbladder morphology and duplication (rare)
- Blood supply to CBD - 3 oclock and 9 oclock
Micro Anatomy
- Functional unit: Acinus or lobule flow from outside to center
- Inflow: Interlobular artery (from hepatic artery) and vein (from portal), into sinusoids lined by hepatocytes
- Outflow: central vein (into hepatic vein)
Hepatocytes: 60% of cellular mass of the liver
- uptake, storage and release of nutrients
- synthesis of glucose, fatty acids, lipids, and plasma proteins (including C-reactive protein and albumin)
- production and secretion of bile
- degradation of toxins
Physiology
- approx 4% of total body mass
- consumes about 28% of the total body blood flow
- 20% of the total oxygen
- 20% of the total body caloric intake
- Blood flow increases after ingestion, decreases with exercise/sympathetic stimulation
- Bile secretion: 1.5L per day
- 80% of volume produced by hepatocytes
- 20% from cells lining the bile ducts further down
Bile Salts – Entero-hepatic circulation
- Primary: cholic acid and chenodeoxycholic
- Excreted and processed by bacteria in GI tract
- Reabsorbed passive in jejunum; active in ileum
- Enter the bloodstream, 90% are extracted by hepatocytes
- Secondary: deoxycholic acid and lithocholic acid created by bacteria digesting primary salts
Bilirubin: breakdown of RBCs
- Binds albumin in blood
- Internalized into hepatocytes
- Conjugated and then secreted with bile
- Deconjugated to urobilinogen in GI tract and reabsorbed with bile
- Some urobilinogen reabsorbed and secreted in urine
Carbohydrate metabolism
- Liver is major site of storage and distributer of glucose
- Stored glycogen; only liver can break it down to form glucose
- Excess CHO is converted to fatty acids and stored in adipose
- After 48hrs glycogen stores are depleted and liver shifts from glycogenolysis to gluconeogenesis
- Substrate for gluconeogenesis is mostly amino acids from muscle breakdown and glycerol from TAG breakdown
Lipid metabolism
- Fatty acids are made in liver in states of excess glucose
- During lipolysis free fatty acids are broken down in the liver
- B-oxidation yields ATP and ketone bodies
- In a fed state FFA undergoes esterification with glycerol to form TAG
- This is in fed state; B-oxidation is in starve state
- Increased amount of fatty acids in the liver can lead to steatosis and eventually steatohepatitis
Protein metabolism
- AA’s not used in peripheral tissues are managed by liver
- Cannot catabolize branch-chain amino acids - Leucine, isoleucine, valine
- Key site of production of many key proteins
- Ceruloplasmin, Fe storage/binding proteins, a1-antitrypsin, albumin, coagulation factors (except 8)
- Metabolism of fat soluble vitamins
- Sole storage site of vitamin A is liver
- Vit D activated (one step) in liver – 25-hydroxylation then in kidney
- K is critical for coagulation factors made in liver
Metabolism of drugs/toxins
- Phase 1 metabolism = oxydation, reduction, hydrolysis
- To make compounds more polar/water soluble and excrete in urine
- Phase 2 = transferase reactions (conjugation)
- Makes compounds inactive/less active
Clinical Evaluation
Assessment of liver function
LFTs: Alk Phos, ALT, AST, Bili
- Transaminases (ALT/AST) most common marker for hepatocyte injury (necrosis)
- AST is found in other organs; ALT is specific to liver
- Are non specific, provide little prognostic value
- Alk phos is made in liver, biliary, bone, intestine, placenta, kidney
- GGT made in liver, spleen, kidney, pancreas, heart, brain
Albumin – not as sensitive to evaluate liver function
Clotting factors – good to evaluate synthetic function of liver
Quantative test for hepatic function
- Not clearly better than scoring scales or clinical observation
- Aminopyrine breath test
- Breath test measuring radiolabeled CO2 after administering radiolabeled aminopyridine
- Not much more valuable than clinical evaluation
Portal vein thrombosis
Isolated splenic varices
Tertiary Bleeding Prophylaxis
- TIPS
- Operative Shunt
- Transplant
Acute variceal bleeding
- Hemorrhagic Shock Resuscitation
- Questionable benefit of rFVIIa in Child's B/C case
- Octreotide (vasopressin used to be used but was causing MIs)
Inhibits release of splanchnic vasodilators (Glucagon)
Direct splanchnic vasoconstrictor
50 mg IV then 50 mg/hr IV for 5 days
- Banding is procedure of choice to control bleeding (80% effective)
- Gastric varices
Gastroesophageal -0 in continuity with esophageal barices
- GOV1 - on lesser curve
- GOV2 - on greater curve - Less responsive to banding, Treated with injuection of fibrin glue or emergent TIPS
Isolated gastric
- IGV 1 - in fundus (most common site with splenic vein thrombosis
- IGV 2 - in gastric body, antrum, or duodenal bulb
- Risk of re-bleeding is greatest within 48 hours
- Urgent Transjugular intrahepatic portosystemic shunt (TIPS)
Fluoro/angio guided tract between hepatic and portal vein
90% effective, 10% acute complications, 25% encephalopathy
Indications
- Refractory variceal bleeding
Bridge to transplant
- Sengstaken blakemore tube
Double balloon system
Temporary control
30% complication rate
Control airway prior
Bridge to TIPS
Shunt surgery
- Non-selective portocaval shunt
Distal splenorenal shunt (warren shunt)
- Effective by decompressing esophagogastric varices while preserving portal venous flow making it pretty much the only shunt done anymore
- Splenic vein connected to left renal vein
- Will worsen ascites
Infectious Disease of the Liver
Pyogenic abscess
- 22/100,000 of hospital admissions
- Pathogenesis: liver is exposed regularly to bacterial load through the portals system
- Biliary tree extension is also common cause
- 75% in right liver, 20% left, 5% caudate; rarely bilateral
- 50% solitary, can be multiloculated or a single cavity
- Common organisms: E coli, Klebsiella pneumoniae, Staph a, Enterococcus, Strep viridans, Bacteroides
Klebsiella – gas forming
Enterococcus and Strep v. – usually polymicrobial
Staph a. – usually solitary organism
- Rare: pseudomonas, proteus, enterobacter, citrobacter, serratia
- Presenting symptoms
Specific: jaundice, RUQ pain, TTP
Only present in 10%
Non specific: vague abd pain, fever, chills, wt loss, cough
- Labs:
Leukocytosis (elevated in 90%), LFTs (60%), Bili (20-50%)
- Imaging
Occasionally seen on CXR
CT great for imaging (sensitivity 95 to 100%)
- Important to differentiate between pygenic and other cystic disease of liver (echinococcal, amebic) - Management is quite different
- Management of pyogenic abscess
IV abx; blood cultures
Percutaneous drainage – if no drain left may need to do repeat aspirations
- Mortality was nearly 100% before IV abx, From 1945 to 1980s mortality was 50%, 1990s to 2000s mortality was 10%; recent studies show 3%
Amebic Abscess
- Epidemiology
Largely tropical and developing nations
E. histolytica is endemic to Mexico, India, Africa, Central/South america
WHO estimates 40-100,000 deaths per year
Estimated that 55% in endemic regions have GI infection
Males are at 10x risk to females
- Pathogenesis
E. histolytica cysts are transmitted fecal-oral route
Trophozoite is released in colon; invades mucosa
- Lab tests
Mild leukocytosis (less so than pyogenic), LFTs and Bili, most common lab abnl is PT/INR
70% will not have amebae in stool; need to check serum anti-amebic antibodies
Present in 90-95% of people
- Acute infection (<10 days): high fever, multiple lesions, more pain
- Chronic infection (>2wks): vague symptoms, 80% single right side lesion
- Imaging
Ultrasound: Rounded lesion abutting capsule
CT: more sensitive and specific
- Treatment: 750mg Flagyl TID
Curative in 90%
- Complications
Rupture (3-17% risk)
Sudden abdominal pain; peritonitis
Mortality for all amebic abscess=5%; after rupture up to 50%
Hydatid Cyst
- Echinococcosis
A zoonosis; dog is definitive host
Sheep is usual intermediate host
Cyst is the larval stage
3 species: Echinococcosis granulosus is the most common, also multilocularis and ligartus
Parasitic embryo releases an oncosphere
Released through the duodenal mucosa into the blood stream
Oncosphere reaches liver (or lung, or brain) and implants and develops larval stage – the cyst
3 weeks after implantation a visible cyst develops
Cyst wall 2 layers; peri-cyst fibrous capsule derived from host tissues
Dead cysts and degraded capsules form a sand in the cyst
Daughter cysts can form
- 75% located in right lobe of liver
- Rupture of cyst can cause severe anaphylactic reaction
- Diagnosis:
Ultrasound: most common modality used worldwide
CT/MRI have excellent sensitivity
- Surgical Management
Anesthesia should have steroids and Epi available in case of anaphylaxis
Important to pack off/drape the field when excising the cyst in case of spillage
Aspirate cyst, inject agent (hypertonic saline)
Cyst is then unroofed, excised, marsupalized, etc
Recurrence from 1-20% (usually less than 5%)
Percutaneous drain – previously contraindicated
- Aspiration and injection of scolicidal agents (20% saline, 95% ethyl alcohol, betadine, hydrogen peroxide)
Recurrent Pyogenic Cholangitis
- Found almost exclusively in Asians (and Asian immigrants)
- Cause is unknown
- Is disease of recurrent infection of biliary tree with GI bacteria
Stones and strictures develop
Not known which occurs first
- Associated with Clonorchis sinensis and Ascaris lumbricoides infections
- Typical patient: young Asian of lower socioeconomic background
- Increased risk of cholangiocarcinoma
- Other complications: choledochoduodenal fistula, pancreatitis, duct obstruction
- Most improve with conservative management
- Surgical management includes CBD exploration, ERCP, percutaneous transhepatic cholangioscopic lithotripsy
- All focused on ductal decompression, stone removal, stricture bypass