Upper GI surgery2

Niamh Bambury

Overview

• Liver• Spleen

Architecture of the liver

• The hepatic lobule is the structural unit of the liver.

• hexagonal arrangement of plates of hepatocytes radiating outward from a central vein in the center.

• At the vertices of the lobule are regularly distributed portal triads, containing a bile duct and a terminal branch of the hepatic artery and portal vein.

Architecture of the liver

•Hexagonal arrangement of plates of hepatocytes radiating outward from a central vein in the center. •At the vertices of the lobule are regularly distributed portal triads

Vasculature of the liver

• 75% of the blood entering the liver is venous blood from the portal vein– The PV is the confluence of the splenic vein and the superior mesenteric vein, which drain the small intestine, pancreas, stomach, and spleen.

• The remaining 25% of the blood supply to the liver is arterial blood from the hepatic artery.

Vasculature of the liver

• Terminal branches of PV and HA empty together and mix as theyenter sinusoids in the liver.

• Sinusoids are distensible vascular channels lined with highly

fenestrated endothelial cells and bounded circumferentially by hepatocytes.

• As blood flows through the sinusoids, a considerable amount of plasma is filtered inthe space between endothelium and hepatocytes (the "space of Disse"), providing a major fraction of the body's lymph.

• Blood flows through the sinusoids and empties into the central vein of each lobule.

• Central veins coalesce into hepatic veins, which leave the liver and empty into the vena cava

Biliary anatomy

• A series of channels and ducts that conveys bile from the liver into the lumen of the small intestine.

• Hepatocytes are arranged in "plates" with their apical surfaces facing and surrounding the sinusoids. The basal faces of adjoining hepatocytes are welded together by junctional complexes to form canaliculi, the first channel in the biliary system.

• A bile canaliculus is not a duct, but rather, the dilated intercellular space between adjacent hepatocytes.

Biliary anatomy

• Hepatocytes secrete bile into canaliculi• These secretions flow parallel to the sinusoids, but in the opposite direction to blood

• Bile flows into bile ducts at the end of the canaliculus,, which is a true duct lined with epithelial cells. Note bile ducts begin in very close proximity to the terminal branches of the portal vein and hepatic artery,

• The grouping of bile duct, hepatic arteriole and portal venule is called a portal triad.

Biliary anatomy

•The apical surface of the hepatocyte faces the sinusoids•The basal surfaces of adjoining hepatocytesare welded together by junctional complexes to form canaliculi

Lymph formation

• Approx half of the lymph formed in the body is formed in the liver.

• Fenestrations in sinusoidal endothelial cells allow fluid and proteins in blood to flow freely into the space between the endothelium and hepatocytes known as the space of Disse forming lymph.

• Lymph flows through the space of Disse to collect in small lymphatic capillaries associated with the portal triads and from there into the systemic lymphatic system.

Lymph flow in the liver

•If pressure in the sinusoids increases above normal, there is a corresponding increase in the rate of lymph production.

•In severe cases this leads to exudation of lymph from the normal channels, and it accumulates in the abdominal cavity as ascitic fluid.

The Liver in phagocytosis

• The liver forms an important part of the phagocytic system.

• Macrophages known as Kupffer cells are situated in the sinusoids.

• Kuppfer cells are actively phagocytic and represent the main cellular system for removal of particulate materials and microbes from the circulation.

• They are located downstream to the blood entering the liver from the gut throught the portal vein . This allows it to effectively police and destroy bacteria entering the liver through breaks in the intestinal epithelium

Physiology of the liver

• Functions– Metabolism, Heat production– Storage– Excretion– Detoxification– Endocrine– Bile production

Metabolism

• Products of digestion are transported by the portal venous system to the liver

• In the liver there are metabolised into products easily used by the body as energy

• Fats-in food – triglyceride– Phospholipids– sterols (principally cholesterol)

• Fats provide 9kcal/g, compared with 4 kcal/g for carbohydrate and protein.

Fat metabolism

• Oxidizises triglycerides to produce energy.

• After digestion, most of the fats are carried in the blood as chylomicrons.

• The main pathways of lipid metabolism are lipolysis, betaoxidation, ketosis, and lipogenesis.

Fat metabolism

• The liver synthesizes and secretes VLDL which is used to facilitate the Beta oxidation of fatty acids if energy is needed from this source

• The liver synthesizes large quantities of cholesterol and phospholipids. Some of this is packaged with lipoproteins and made available to the rest of the body. The remainder is excreted in bile as cholesterol or after conversion to bile acids.

Protein metabolism

• Peptidesamino acids in the liver. These can be used for gluconeogenesis

• The liver synthesizes all non essential amino acids

• Removal of ammonia from the body by synthesis of urea. Ammonia is very toxic and if not rapidly and efficiently removed from the circulation, will result in central nervous system disease.

• Also synthesizes plasma proteins and enzymes– Albumin– Fibrinogen

Carbohydrate metabolism

• Processes include – Glycogenesis Excess glucose entering the blood after a meal is rapidly taken up by the liver and sequestered as the large polymer, glycogen

– GlycolysisGlycolysis-releases energy from glucose or glycogen

– Gluconeogenesis-formation of glucose from noncarbohydrate sources, such as certain amino acids and the glycerol fraction of fats when carbohydrate intake is limited.

Storage

• Vitamins ADEK• Minerals eg Copper iron, Ferritin

• Glucose in the form of gycogen

Excretion

• Ammonia– formed by the breakdown of proteins

– converted into urea

• Bacteria– Kupffer cells

• Cholesterol and bile pigments

Excretion

• Hormones– Degraded by the cytochrome p450 system•Steroid hormones(oestrogen)•Protein hormones(insulin, ADH)•Catecholamines

• Drugs and toxins– Degraded by the cytochrome p450 system

Bile Production

• Bile consists of– Products for excretion

• Bile pigments(red blood cells)• Cholesterol(fat metabolism)• Fat soluble drugs and toxins

– Products to aid digestion• Bile salts to emulsify fats(cholic ,chenodeoxycholic acid)

• Lecithin to help make cholesterol soluble• Inorganic salts-including bicarbonate to neutralise duodenal contents

Enterohepatic circulation of bile

salts• Bile salts aid solubility in the jejunum• Bacteria convert the bile salts into secondary acids

• These are then resorbed in the terminal ileum as primary bile salts

• These return to the liver via the portal circulation

• Deficiency occurs in the context of disease or resection of the terminal ileum. This results in steatorrhoea and deficiency in fat soluble vitamins

Liver function tests-What’s it all about?

• Alanine transaminase (ALT)– an enzyme present in hepatocytes – cell damage leaks it into the blood– raised in acute liver damage eg viral hepatitis or paracetamol overdose.

• Aspartate transaminase (AST) – enzyme associated with liver parenchymal cells.

– not specific to the liver also present in red blood cells, and cardiac and skeletal muscle

– The ratio of AST to ALT is sometimes useful in differentiating between causes of liver damage.

Liver function tests-What’s it all about?

• Alkaline phosphatase (ALP) – enzyme in the cells lining the biliary ducts of the liver

– rise with large bile duct obstruction, intrahepatic cholestasis or infiltrative diseases of the liver.

– also present in bone

• Total bilirubin – breakdown product of heme (a part of haemoglobin in red blood cells).

– The liver is responsible for clearing the blood of bilirubin.

– In injury increased levels cause jaundice

Bilirubin excretion

• Erythrocyteshemoglobin heme unconjugated bilirubin in the kidney. (Not soluble in water) bound to albumin liver conjugated with glucuronic acid(water soluble)

• At this stage it can go down a number of routes– 1) goes into the bile and thus into the small intestine.

– 2)conjugated bilirubin metabolised by colonic bacteria to urobilinogen stercobilinogen stercobilin(brown color of faeces)

– 3)Some of the urobilinogen is reabsorbed and excreted in the urine

Liver function tests-What’s it all about?

• Bilirubin revisited– Direct versus indirect– An increase in direct bilirubin/conjugated bilirubin suggests the problem is not being able to excrete it eg bile duct obstruction by gallstones or cancer.

– No increase in direct bilirubin suggests the liver is unable to conjugate bilirubin eg haemolysis, viral hepatitis, or cirrhosis

Liver function tests

• Gamma glutamyl transpeptidase (GGT)– specific to the liver– more sensitive marker for cholestatic damage than ALP

– may be elevated with even minor liver dysfunction

– raised in alcohol toxicity (acute and chronic). In some laboratories,

Liver function tests

• Coagulation test (e.g. INR)– The liver is responsible for the production of coagulation factors

– only increased if the liver is so damaged that synthesis of vitamin K-dependent coagulation factors has been impaired

• Serum glucose (BG, Glu)– Gluconeogenesis I the last function to be lost in the setting of fulminant liver failure.

• Lactate dehydrogenase (LDH)– enzyme found in many body tissues, including the liver. Elevated levels may indicate liver damage.

Jaundice

• Jaundice– a yellowish discoloration of the skin, the conjunctival membranes over the sclerae and other mucous membranes

– Due to hyperbilirubinemia – the concentration of bilirubin in the plasma must exceed three times the usual value for the coloration to be noticable

The classification of Jaundice

• Pre hepatic• Hepatic • Post hepatic

Pre-hepatic jaundice

• Due to an increased rate of haemolysis eg – malaria – sickle cell anemia– spherocytosis – glucose 6-phosphate dehydrogenase deficiency

• Laboratory findings include:– Urine: no bilirubin present– Serum: increased unconjugated/indirect bilirubin.

Hepatic jaundice

• Cell necrosis reduces the liver's ability to metabolise and excrete bilirubin eg– acute hepatitis– hepatotoxicity – alcoholic liver disease– Congenital disorders

• Laboratory findings include:– Urine: Conjugated bilirubin present

Congenital hyperbilirubinaemia

• Metabolic defects in – 1)intrahepatic conjugation

•Crigler-Najjar(unconj)

– 2)hepatic uptake•Gilberts-5%, males, auto dominant

– 3)excretion of bilirubin•Dubin-Johnson (conjugated)-recessive

•Rotor Syndrome

Post-hepatic

• Leads to obstructive jaundice as there is blockage of bile flow eg.– gallstones in the common bile duct– pancreatic cancer in the head of the pancreas .

• Symptoms include– presence of pale stools– dark urine – pruritus

• Laboratory tests – liver function tests

Portal hypertension

• A portal pressure gradient of >5mmHG(difference in pressure between the portal and hepatic veins)

• Prehepatic causes– Portal vein thrombosis

• Hepatic causes– Cirrhosis– Hepatic mets

• Post hepatic– Budd Chiari(thrombosis of hepatic veins)

Budd-Chiari syndrome

• Occlusion of the hepatic veins

• presents with triad of – abdominal pain– ascites – hepatomegaly

• Eventually leads to encephalopathy

Budd Chiari

• Genetic tendencies include– Protein C/Protein S deficiency– the Factor V Leiden

• Risk factors– OCP, oestrogen containing– Pregnancy– Trauma

Treatment of BCS

• Surgical shunts to divert blood flow around the obstruction or the liver itself

• Transjugular intrahepatic portosystemic shunt (TIPS)– lower procedure-related mortality

• Angioplasty– stenosis or vena caval obstruction

• Liver transplant

Complications of Portal hypertension

• Splenomegaly– sequestration of platelets– Leukopenia, thrombocytopaenia-hypertrophy of splenic substance

• Ascites Albuminintravascular oncotic pressure

– Lymphatic overflowlymph flow through thoracic duct exceeds capacity

aldosteroneNa & H2O retention

Complications of Portal hypertension

• Portosystemic shuntingvarices– Gastric, oesophageal– Periumbilical– Retroperitoneal– Rectal– Diaphragmatic

Acute Liver injury

• Causes– Viral– Alcohol– Drugs– Obstruction

Viral Hepatitis

• Hepatitis A– Faeco-oral spread– No carrier state– Incubation period-15-40 days– Serology- IgM class antibody to HAV

Viral Hepatitis

• Hepatitis B– Spread-

•blood•needles•venerally

– Carrier state exists– Incubation period-50-180 days

Viral hepatitis

– Hepatitis B cont’d– Serology

•HbsAg-Hx of infection •HbeAg active infection

– Long term sequelae•Chronic hepatitis•Cirrhosis•Implicated in pathogenesis of hepatocellular carcinoma

Viral hepatitis

• Hepatitis C– Spread-

•blood•needles•venerally

– Carrier state exists– Incubation period-40-55 days

Viral hepatitis

• Hepatitis C cont’d• Serology-

– Anti-HCV antibody– Increase in transaminases

• Sequelae– chronic state – cirrhosis

Alcoholic liver injury

• Pathogenesis– Cellular energy diverted to metabolism of alcohol-accumulation of fat in liver cells

– Alcohol metabolites bind to liver proteins-injured hepatocytes

– Alcohol stimulates collagen synthesis- fibrosis and cirrhosis

– Linking of portal tracts by fibroblasts- nodular regeneration of liver cells

Alcoholic liver injury

• Histology– Steatosis-fatty change– Mallory’s hyaline

Acute Biliary Obstruction

• Secondary to cholelithiasis• If superimposed infection cholangitis• Bile accumulates in canaliculi and ducts

extravasation of bile into liver tissuenecrosis

Repeated episodes of obstruction portal tract fibrosis& nodular regeneration

2 biliary cirrhosis

Chronic Liver Disease

• Primary Haemochromotosis– Excess Iron absorption from small intestine

– Defect at Chromosome 6 near HLA-A locus

– Iron accumulates in Kupffer cells, bile duct epithelium and portal tracts hepatic fibrosiscirrhosis

– Deposition of Fe in pancreatic isletsDiabetes

• Secondary Haemochromotosis•Excess dietary iron•Patenteral administration•Excessive blood transfusion

Wilsons

• Inherited disorder of copper metabolism

• Copper accumulates in basal ganglianeurological disability

• Kayser Fleischer rings in cornea• Labs- low ceruloplasmin• Treatment-penecillamine

Alpha-Antitrypsin deficiency

• Normally synthesized in the liver and excreted into blood

• protects the lungs from the neutrophil elastase enzyme, which disrupts connective tissue

• Carrier state exists• Homozygotes

– pulmonary emphysema– hepatic cirrhosis

• Treatment-– IV infusions of A1AT protein– liver or lung transplant

Autoimmune Liver Disease

• Autoimmune Hepatitis• Primary biliary cirrhosis• Sclerosing cholangitis

Autoimmune Hepatitis

• Females

• Histology-hepatitis

• Serology- autoantibodies found eg antinuclear antibody (ANA), smooth muscle antibody(SMA)

• Increased IgG level and transaminases

• Diagnosis always requires liver biopsy

Primary biliary cirrhosis

• Females• Destruction of small intrahepatic ducts leading to cirrhosis

• Copper accumulates in the liver• Serology

ALP+ IgM– Anti-mitochondrial antibodies

• Features-Jaundice,Pruritus,Xanthelasma

• Treatment-Liver transplant

Sclerosing Cholangitis

• Chronic inflammatory process• Affects intra and extrahepatic ducts• Ducts are surrounded by inflammatory

infiltrateimpedes the flow of bile to the gut, which can ultimately lead to liver cirrhosis and failure

• underlying cause of the inflammation is believed to be autoimmunity.

• Eventually leads to fibrosisobliteration of ductssecondary biliary cirrhosis

• Associated with Ulcerative Colitis

Sclerosing Cholangitis

• Labs– pANCA– ANA– Anti-smooth ms antibodies – Elevated bilirubin

• Treatment– Liver transplant

• Associated with cholangiocarcinoma

Tumours

• Hepatocellular/ Hepatoma• Cholangiocarcinoma• Haemangioma• Focal nodular hyperplasia• Angiosarcoma• Hepatoblastoma

Hepatocellular carcinoma

• Highest incidence is seen in East Africa and South-east Asia

• Male : female ratio = 4:1 • In Europe peak age at presentation is 80 years

• In Africa and Asia peak presentation is 40 years

Presentation

• Right hypochondrial pain/mass• As with all malignancy- weight loss, loss of appetite

• Jaundice is a late sign

Aetiology

• multifactorial• HBV infection (not independent risk factor)

• HCV infection• cirrhotic liver• Mycotoxins - e.g. aflatoxin produced by Aspergillus flavus

• Alcohol • Anabolic steroids • Primary liver diseases - e.g. primary biliary cirrhosis, haemochromatosis

Investigations

• FBC– Anaemia: Low hemoglobin may be related to bleeding from varices or other sources.

– Thrombocytopenia: A platelet count below 100,000/mL is highly suggestive of significant portal hypertension/splenomegaly.

• U&Es– Hyponatremia is commonly found in patients with cirrhosis and ascites and may be a marker of advanced liver disease.

– ↑creatinine intrinsic renal disease or hepatorenal syndrome.

Investigations

• Coag screen- – ↑ INR -impairment of hepatic function that may preclude resection.

• LFTs – (AST/ALT) -active hepatitis due to viral infection, current alcohol use, or other causes.

– Increased bilirubin level -advanced liver disease.

• Glucose– Hypoglycemia may represent end-stage liver disease (no glycogen stores).

Alpha-fetoprotein

• Foetal serum protein produced by the yolk sac and liver

• ↑serum levels seen in 70-90% of patients with HCC

• May be mild elevation ↑ in serum levels in the context of hepatitis and cirrhosis

• Serum levels correlate with tumour size • Rate of increase in serum levels correlate with growth of tumour

• Tumour resection results in a fall in serum concentrations

• Serial assessment useful in measuring response to treatment

Finding the underlying cause

• Hepatitic screen– HBsAg/anti-HBc, anti-HCV - Viral hepatitis (current/past)

• Iron studies– Increased iron saturation (>50%) - Underlying hemochromatosis

• alpha-1-antitrypsin levels – Low in Alpha-1-antitrypsine deficiency

• Tumour markers– alpha fetoprotein - Levels greater than 400 ng/mL diagnostic

Staging

• Prognosis is dependant on tumor characteristics – Size– Location– Degree of underlying liver disease.

• the tumor size is predictive of outcome, as it predicts the likelihood of major venous

• The traditional pathological TNM (tumor, node, metastasis) staging system is used

Imaging

• Ultrasound – appears as a round or oval mass with sharp, smooth boundaries

– range of echogenicity, from hypoechoic to hyperechoic

• Doppler analysis useful as HCC has a significant arterial blood supply in comparison to regenerative nodules

Imaging

• CT– a hypervascular pattern with arterial enhancement

– tumor capsule– variable attenuation within the tumor

– Smaller lesions may be missed– 67% sensitivity

CT Scan

MRI

• sensitivity 81%

Hepatic decompensation

• Abnormal clearance of proteins absorbed from the intestine, leading to a build up of ammonia and hepatic encephalopathy (a build up of toxic substances such as ammonia that leads to nervous system changes and eventual brain damage).

• Elevated bilirubin levels, leading to jaundice.

• ascites• Portal hypertension leading to varices

Treatment options

• Chemoembolization• Ablation• Chemotherapy• Surgical resection• Liver transplant

Radio-frequency ablation

• Can extend life and potentially downstage the tumor to permit transplantation or resection.

• A needle with an exposed electrode is inserted into the tumour under u/s guidance

• Radiofrequency energy is emitted and is converted to heat in the electrode which causes tumour necrosis

Chemoembolization

• Transcatheter arterial chemoembolization• Used mostly for palliative purposes• Performed by interventional radiologist

– cannulate the feeding artery to the tumor – deliver high local doses of chemotherapy,eg mitomycin C.

– To prevent systemic toxicity, the feeding artery is occluded with coils to prevent flow.

– Note most hepatocellular carcinomas derive 80-85% of their blood flow from the hepatic artery, Normal parenchyma derives most of it’s blood supply from the portal vein so is largely unaffected by this procedure

Chemoembolization

• Contraindicated in patients with advanced cirrhosis as it causes ischemic injury which can lead to a rapid decline in liver function with worsening encephalopathy, increased ascites, and, potentially, death.

Chemotherapy

• Hepatocellular carcinoma is minimally responsive to systemic chemotherapy.

• Doxorubicin-based regimens appear to have the greatest efficacy with response rates of 20-30%

• No apparent benefit with the use of adjuvant chemotherapy following resection