Dr. Darli

NNcvPortal & hepatic sinusoidhepatocyteGall bladderHepatocyte injury by virus, alcohol or drugBallooning, fatty change apoptosis or necrosis with variable distributionVascular disease, congestion, infarctionInflammation, lymphocyte, neutrophil, granulomaRegeneration,fibrosisCirrhosis and?cancerexcretionCPVCPARASITES AND TUMOURSconjugationAVD12345,6ItoRBC

1.Chronic passive venous congestion of the liver CPVCConstrictive pericarditis, CCF are main causes for back pressureCV are congested and centrilobular necrosis occur.Periportal region: relatively less ischemia compare to the hepatocytes.Alternate red color due to congestion and pale color due to fat give nutmeg appearanceLong standing cases end up in cardiac cirrhosiscan be the reason for nonspecific symptoms like flatulence,indigestion and right hypochondrial discomfort

5. Cirrhosis of the liverOne of the top 10 causes of death in the western world.It is characterized by:1. hepatocyte injury of many causes.2. regeneration of remaining cells to form nodules.3. fibrosis replacing the damaged tissue.4. loss of global architecture because of the whole process.5. reorganised vascular architecture resulting in shuntsCauses of the cirrhosis Alcoholic 60-70%Post viral infection-HBV 10%Biliary 5-10%Haemochromatosis 5%Wilsons disease, alfa-1 AT deficiencyCryptogenic (no known cause) 10-15%Others: galactosemia, cardiac, syphilis.

Pathogenesis***Extensive fibrosis with type I and III collagen synthesis in the lobulesCells of Ito are the source of collagen. They are stimulated by TNF-a, TGF b, IL, destruction of extracellular matrix and toxins. Remaining cells regenerate into irregular nodules.Fibrosis and nodule formation results in disorganization of sinusoids, they become like capillaries and hepatocyte isolation resulting in decreased secretion of albumin, clotting proteins and lipoproteins. anastomosis results in high pressure in capillaries and establishment of shunts.Bile duct obliteration results in jaundice.Increased HP, hypoalbuminemia, increased thoracic duct flow, osmotic effects, sodium retention all lead to ascitis and edema. congestion leads to splenomegaly.

1. necrosis.2. regeneration->nodule.3. fibrosis.4. vascular changePoint of no return32

Macronodular cirrhosis

Hepatic failure80-90% cell destruction- loss of functionVH, drugs: INH, acetaminophen, mushroom, alcohol are some of the causesGI bleed, infection, electrolyte disturbance, surgery, CCF hasten failureC/F: Jaundice, hypoalbuminemia, hyperammonemia, fetor hepaticus, palmar erythema, spider nevii. hypogonadism, gynecomastia, ARDS, uremia, coagulopathy, encephalopathy, hepatorenal syndrome and multi organ failure.

JaundiceYellow discoloration of skin & sclera due to excess serum bilirubin. >40umol/l, (3mg/dl)Conjugated & Unconjugated types Obstructive & Non Obstructive (clinical)Pre-Hepatic, Hepatic & Post Hepatic typesJaundice - Not necessarily liver disease *

Ascites in Cirrhosis

Gynaecomastia in cirrhosisPorta-systemic anastomosis: Prominent abdominal veins.

Pathophysiology of portal hypertensionEdemahypoalbuminaemiaAscitesSecondary aldosteronismPortal hypertensionHypoalbuminemiaHematemesis- rupture esophageal varices due to portal hypertensionSpidernaevi- hyperestrogenismPurpura and bleed- reduced clotting factorsComa- bacterial metabolitesInfection- reduced Kupffer cell no. and function

Blood: Conjugated & UnconjugatedStool StercobilinUrine Urobilinogen

Causes of PHTPre- sinusoidalPortal fibrosis due toSarcoidosisSchistosomiasisHepatoportal sclerosisCirrhosisSinusoidalCirrhosisPost- sinusoidalBudd-Chiari syndrome (Thrombosis of hepatic veins)Tumors

Hemodynamic changes proximal or distal to sinusoids or at sinusoid.

Increased portal vascular resistance and intrahepatic shunting between high pressure hepatic artery and portal veinsPathogenesis of portal HT

Primary carcinoma liverCan be hepatocellular (90%) /cholangiocarcinoma (10%)Most common visceral cancerIn developing countries vertical transmission of infection from mother to baby leading to carrier state and cancer occurs around 40yrIn developed countries after 60yrs because of cirrhosis due to HCV or alcohol or hemochromatosis

Pathogenesis.HBV virion integrates and as regeneration occurs mutations take place. protein X is producedIt has insulin GF-property and binds to p53 resulting in its growth suppressor activity.Aflotoxins in some food integrate with liver cell DNA and mutating p53,(in subsaharan Africa and china genetically people may lack enzymes for detoxifying aflotoxins)Cirrhosis due to HCV or alcohol

Morphology.Gross.as unifocal nodule, multifocal nodule or diffusely infiltrative type. All cause liver enlargementNodule may look pale or greenishInvasion of tumour to portal vein/IVF seen

Microscopy.pattern varies from well differentiated to highly anaplasticTrabecular, acinar, pseudoglandular patterns can occur.Features of anaplasia, inreased N:C ratio, nucleoli and intranuclear inclusions.

SECONDARY TUMOURSMetastasis to liver from other organs is more common than primaryMetastasis from cancer anywhere in the body can be found in liver. Most from breast, lung, colon and stomach caLiver is enlarged, nodular with umbilicationThey can be asymptomatic.

Liver cystsSimple cyst / Polycystic diseaseSmall multiple cyts (10-20mm)Hydatid cystsEchinococcus granulosusLamainated fibrous wallNumerous daughter cysts-rupture- anaphylactic shock in sensitized patientsCholedocheal cystsRare, intra or extrahepatic cysts of bile ductsPredispose to cholangitis

Acute pancreatitisAutodigestion of the pancreas by its escaped enzymes Clinical features (Symptoms) Pain (sudden,intense,continuous, upper abdomen back, bizarre position)

Nausea and VomitingInvestigations: 1-Blood testsSerum amylase and lipase levels may be slightly elevated in chronic pancreatitis; high levels are found only during acute attacks of pancreatitis.

-Abdominal x-ray: Pancreatic calcifications, often considered pathognomonic of chronic pancreatitis, are observed in approximately 30% of cases.

Etiology: (GET SMASHED)G: Gallstone.(common)E: Ethanol. T: Truma.. S: Steroid.. M: Mumps.A: Alcoholism (common) or autoimmune.S: Scorpion bits.H: Hyperlipidemia.E: ERCP.D: Drugs: Thiazide, Azathioprine.

Pathophysiology:When the activation of digestive proenzymes occurs in pancreatic duct system or aciner cells, the inflammation is the result. Oedema or obstruction of ampulla of veter resulting in reflexes Of bile into pancreatic duct or to acinar cells.Pancreas shows edema & necrosis.(10%-30% mortality rate).The release of digestive enzymes lead to fat necrosis in the pancreas &peritoneal cavity.

DDx:Perforated peptic ulcer.Acute cholecystitis & biliary colic.Acute Int obstruction.Renal colic.DKA.

Clinical Features:Hx :Abdomenal pain: sever, stay 12-24h after eating a large meal or consuming alcohol,rediate to the back or to the shoulder, pain is worse by walking or laying supine & better after sitting or leaning forward.N &V.Shock in sever case.Severe acute pancreatitis may cause dehydration and low blood pressure. The heart, lungs, or kidneys can fail. If bleeding occurs in the pancreas, shock and even death may follow.Abd Ex:Tenderness in epigastric & guarding of Abd muscles.Mild Abd distention( if the purulytic ileus develop).In sever advanced case:Grey turners sign.Cullens sign.

Investigation:Serum amylase; It stays 48-72h then become normal.Serum lipase; (diagnostic test) It elevated for 7-14 days.Other: -WBC (15000-30000). -LDH>500 U/dl - Glucose. - Albumin. - Ca in serum. - AST.Bilurbin,Alkaline Ph. - ABG show Hypoxia.

Xray of Abdomen: -gall stones. -Sentinel loop: air filled SI in the LUQ. -Colon cut off sign: gas-filled seg of transverous colon abruptly ending at the area of pancreatic inflammation.

U/S: -Gall stones. -Bilary obstruction. -Psudocyst.

CT: (is the dignostic even with normal amylase). -enlarged pancreas. -Psudocyst. -Abscess & hemorrhage. -Presence of gas bubbles in CT scan indicate pancreatic abscess.

COMPLICATION:Shock & renal failure:(pancritic necrosis is association with leakage of fluid in the pancreatic bed & also illus with fluid filled the bowl leading to tubular necrosis).Hypo Ca: sequestration of Ca in fat necrosis.(sponification)Hypoalbuminemia: Capillary permeability.Hyperglucemia: due to disruption of pancreatic islets. Hypoxia: Resp distress.

6- Pancreatic : -Necrosis. -Abscess. -Pseudocystis:a circumscribed collection of fluid rich in pancreatic enzymes, blood, and necrotic tissue, typically located in the lesser sac of the abdomen. Pancreatic pseudocysts are usually complications of pncreatitis. The prefix pseudo- (Greek for "false") distinguishes them from true cysts, which are lined by epithelium; pseudocysts are lined with granulation tissues.

7- GI: -UGI Bleeding. -duodenal obstruction. -Gastric or duodenal erosion. -splenic or portal vein thrombosis. - compression by pancreatic mass. - compression of common bile duct.

Assesment of severity (Ransons Criteria)3 or more indicate sever pancreatitis:Age > 55 Y/O.Blood glucose > 200 mg/dl.WBC > 16000AST > 250 IU/L.Serum LDH >350 IU/L.

Development of the following in the first 48h indicate a worsening porgnosis: (PANCREAS)P: PO2 < 8KPa.A: Age > 55y.N: Neutrophil > 15000000000L.C: Calcium 16 mmol/L)E: Enzymes: -LDH>600 iu/L. -AST >200 iu/L.A: Albumin: 10 mm0l/L.

Chronic Pancreatitis:

Is chronic inflammatory disease characterized by fibrosis & dustruction of exocraine pancreatic tissues.Both forms of pancreatitis occur more often in men than women. Chronic pancreatitis often develops in people who are between the ages of 30 and 40.EtiologyAlcoholism.(common)Malnutrition.Stnosis of ampulla of veter.

C/F:Abd pain.Weight loss, Aneroxia, Avoidness of food bcz of post- prandial pain, Malabsorbtion.Steatorrhea.On Ex: Epigastric pain.

Abd xray : clacified pancreas.U/S AbdCT Abd: : atrophy,clacification.ERCP.Investigation

What is Pancreatic CancerA disease in which malignant (cancer) cells are found in the tissues of the pancreas

4th leading cause of death from cancer in males5th in femalesAffects people at 70-80 y/o60-80% occur at the head of the pancreas

Laboratory TestsBLOOD TESTS:Amylase: (normal value: 30-110 U/L) the blood level of amylase is usually significantly elevated>>Critical value: >Normal values: bilirubin= 0.2-1.3 mg/dl , phosphatase= 38-126 U/L>>8-12 hours fasting for more accurate results

CEA (Carcinoembryonic antigen): a tumor marker used as a monitoring toolNormal Value:

CA 19-9 (Cancer Antigen 19-9) testing: Cancer antigen 19-9 (CA 19-9) is aproteinthat exists on the surface of certain cancer cells. >>a tumor marker for pancreatic cancer; it may be used to monitor for cancer recurrence but is not useful for detection or diagnosis>>Normal Value: >CA 19-9 >37 U/mL result may indicate pancreatic cancer >>CA 19-9 is elevated in about 70% of people with advancedpancreatic cancer

Computed tomography (CT) scan: useful for detecting pancreatic masses and checking for metastasized cancerBiopsy: used to confirm diagnosis of cancer, often in conjunction with CT scan.

The primary filtering element for the blood. Acts as a filter against foreign organisms that infect the blood stream.The site of red blood cell and platelet storage.Filters out old red blood cells and recycles them.

TUMORSSpleen - mostly secondary involvementnon-Hodgkins Lymphoma most common malignancyMain Tx: Chemo +/- RTSpleen is the primary site10% Hodgkins disease30% of resected spleens (staging procedure) have (+) histologyHairy cell leukemiaResect for symptomatic splenomegalyImproved survivalCML & CLLsymptomatic splenomegaly = splenectomy