Lecture 26

Question 1

Cholestasis Cells

Answer 1

Cholestatic hepatocytes are enlarged wth dilated canalicular spaces
Apoptotic ells may be seen
Kupffer cells frequently contain regurgitated bile pigments

Question 2

Cholestatis

Answer 2

Obstructive liver disease

1. -Intra hepatic (bile ducts or canaliculi within liver)
2. -Extrahepatic (common bile duct of head of pancreas)

Question 3

Autoimmune Cholangiopathies

Answer 3

• autoimmune damage to bile ducts or bile canaliculi(rare or uncommon. react against own body)
  1. Primary Biliary Cirrhosis
• autoimmune disorder leading to destruction of bile canaliculi
• expansion of portal tract by infiltrate of lymphocytes and plasma cells (seen in normal immunological response) (granulomatous reaction to bile duct undergoing destruction)
• fine nodularity and intense bile staining (of end stage biliary cirrhosis)
  2. Primary Sclerosing Cholangitis
• autoimmune disorder leading to scarring of the bile ducts

Question 4

Cholestasis of Sepsis

Answer 4

patients with blood cancers/infections with effected immune system
-abnormal liver enzymes and obstructive patterns (of sepsis)

Sepsis can affect the liver through:

• Direct effets of intrahepatic infection (liver abcess, bacterial cholangitis (of bile ducts))
• Ischaemia related to hypotension(shock)
• Circulating microbial products (particularly in context of gram-negative (bacteria e.g E. coli, crebseala, pseudotomas) infection (this is most likely to lead to cholestatic picture))

Question 5

Circulatory Disorders: Impaired Blood Inflow

Answer 5

Impaired blood inflow:
Portal vein obstruction (primary liver disease/cirhossis)
Intra or Extrahepatic thrombosis (increase pressure and reverse flow)
—>
1. Esophageal varices (opening up of other capillary plexuses)
2. Splenomegaly (increased pressure of splenic vein)
3. Intestinal congestion

Question 6

Circulatory Disorders: Impaired Intrahepatic Blood Inflow

Answer 6

Impaired Intrahepatic Blood flow:
Cirrhosis
Sinusoid occlusion
-->
1. Ascites (cirrhosis)
2. Esophageal Varices (cirrhosis)
3. Hepatomegaly
4. Elevated amniotransferases

Question 7

Circulatory Disorders: Hepatic Vein Outflow Obstructon

Answer 7

(obstruction in venous sinuses)
Hepatic Vein Outflow Obstruction
Hepatic vein thrombosis (Budd-chiari syndrome)
Sinusoidal Obstructive syndrome
--->
1. Ascites
2. Hepatomegaly
3. Abdominal pain
4. Elevated aminotransferases
5. Jaundice

Question 8

Typical blood flow obstruction in liver

Answer 8

Normally venous

• can occur at multiple places
• will causes similar presentation (ascites, pot splenomegally)

Question 9

Liver tumours

Answer 9

1. Benign Neoplasms
   - Cavernous haemangiomas
   - Hepatocellular adenomas
2. Malignant Neoplasms
   - Hepatocellular Carcinoma (/hepatoma. Complication of cirrhosis (Hep B, C, haemoachromatosis, alcohol). Primary tumour of hepatocytes.)
   - Heptoblastoma
   - Cholangiocarcinoma
   - Hepatic Metastases (most common type of cancer. Secondary cancer. Metastatic spread from Primary Bowel or Colorectal cancer)

Question 10

Hepatocellular Carcinoma

Answer 10

tumour cells on background of chirrosis

Question 11

Hepatic Metastases from adenocarcinoma colon

Answer 11

Multiple hepatic metastases

Question 12

Pancreatic and Gall Bladder Pathology

Answer 12

Pancreatic pathology:
1. Acute and chronic pancreatitis (inflammation)
2. Pancreatic adenocarcinoma (cancers)
Gall Bladder Pathology:
1. Acute and chronic cholecystitis (usually gall stone consequence)
2. Gall bladder adencarcinoma

Question 13

You are on your surgical placement when a 40 year old NZ European woman presents to the emergency department with sudden onset abdominal pain. She finds the pain severe and she has been vomiting. She has no relevant medical history. You go to see her with the surgical registrar.

Answer 13

Acute pancreatitis?

Question 14

Normal Pancreas

Answer 14

Endocrine and Exocrine function
“Hidden” organ
-sits deep, tucked into 2nd part of duodenum. Therefore clinical signs of pancreas are often late and non-specific (may relate to gallbaldder/gastic/duodenal mucosa)

Question 15

Pancreas Exocrine function

Answer 15

Composed of acinar cells and ducts
Acini cells –> ductles –> Pancreatic duct –> common bile duct at ampulla joining
Acinar cells contain zymogen granules (when cleaved for potential proteases, lipases and elastases) (proenzymes that can be activated)
“perfect storm around acute and potent inflammatory response”
Zymogens= inactive enzyme precursors for trypsin, chromotrypsin, amylase, lipase, nuclease, elastase

Question 16

Pancreas Endocrine function

Answer 16

Islets of Langerhans
-Alpha and Beta cells, encoding for number of homrones for metabolic pathway:
Secrete insulin, glucagon and other hormones
-Main pathology: Type 1 and 2 Diabetes Mellitus

Question 17

Pathology of the Pancreas

Answer 17

Congenital/Genetic: Cystic Fibrosis
Inflammatory/Infective: Acute and chronic Pancreatitis
Malignant: Carcinoma of the pancreas

Question 18

Acute Pancreatitis

Answer 18

Inflammation of the pancreas- associated with acinar cell injury
Swollen, Red, Vasodilation, Edmeatis
-Spectrum of severity duration and severity
-Mild 60-70% of cases- low mortality (majority of pancreatitis attacks)
-Severe 30-40% cases, 20-30% mortality (life threatening, usually linked to multi-organ failure as complication of pancreatitis)

Question 19

Key features of inflammation

Answer 19

Swollen
Red
Vasodilation
Edmeatis

Question 20

Etiology of Pancreatitis

Answer 20

1. Metabolic: Alcohol (most common)
2. Mechanical: Gallstone (obstruction, increased pressure, ischaemia and damage to pancreatic cells. Most common), trauma (damage to pancreatic acini cells)
   80-90% of pancreatitis patients = attributed to gallstone/cholilothiasis, or direct alcohol infection
3. Vascular: Shock (trauma-hypotension, or sepsis-hypotension or reduced blood supply. Primarily with shock see toxicity (renal and neurological) can see pancreatic toxicity as consequence) Vasculitis(inflammation of arterial vessels, can effect blood supply to pancreas, can damage acinar cell damage)
4. Infection: Mumps (also traditionally effect salivary gland- viral illness of parotid glands or enlargement of submandibular gland)

Question 21

Pathology of Pancreas

Answer 21

Autodigestion of pancreatic enzymes
-damage to acinar cells, releases pancreatic enzymes, which damages pancreatic tissue —continues same cycle
Cell injury response mediated by inflammatory cytokines (secondary inflammatory response) (TNFa, interlukin 6 and 2)-inducing inflammatory reaction

Question 22

Consequences of Pancreatic Protease enzyme release

Answer 22

destruction of acini, ducts, islets

-release and activate further enzymes

Question 23

Consequences of Pancreatic Lipases enzyme release

Answer 23

Fat necrosis- pancreas and other sites

Question 24

Consequences of Pancreatic Elastases enzyme release

Answer 24

Blood vessel destruction leading to interstitial haemorrhage (into inflamed tissue)

Question 25

Pancreatic Cell injury response caused as a consequence of enzyme release

Answer 25

Inflammation, Oedema, Imapired blood flow, Ischaemia | -significant inflammatory response and potential life threatening illness

Question 26

Acute pancreatitis post mortom

Answer 26

Oedemitis Pink and Erythrotheamtis- due to vasodilation of BV Dark areas of necrosis Hemorrhage into pancreatic tissue (due to inflammatory response and enzyme release)

Question 27

What triggers the acute event?

Answer 27

Obstruction of the pancreatic duct (in common bile duct and ampulla of vata and pancreatic duct. Normal pancreatic secretions wont be secreted into duodenum, increased presure, oedema, reduced blood supply, eventually damage acinar cells, enzyme release) Direct injury to acinar cells

Question 28

Duct obstruction

Answer 28

1. Cholelithiasis (gallstones) 2. ampullary Obstruction (tumour) 3. Chronic Alcoholism (thickened pancreatic secretions which obstruct pancreatic duct) 4. Ductal concretions - -> Interstitial Edema - -> Impaired Blood Flow - -> Ischaemia - -> eventually Damage to acinar cells

Question 29

Acinar Cell Injury

Answer 29

1. Alcohol 2. Drugs 3. Trauma (car crash) 4. Viruses (e.g. mumps virus) 5. Ischemia (reduced blood supply from shock or vasculitis) - -> directly damage acinar cells

Question 30

Pancreatic Ischaemia onflow steps

Answer 30

Intracellular acitvation of trypsinogen --> Intracellular activation and retention of other proenzymes --> acinar cell injury --> Proteolysis(Proteases) + Fat necrosis (lipase, phospholipase) + Hemorrhage (elastase/damages BV) or --> Acinar cel injury response --> interstitial Inflammation (release of inflammatory cytokines) ---> Acute Pancreatitis

Question 31

Hereditary

Answer 31

Mutations of cationic trypsinogen | --> Intracellular activation fo trypsinogen

Question 32

Clinical features of Acute pancreatitis

Answer 32

Acute abdominal pain - epigastric (upper abdominal pain) Nausea and vomiting (as closely associated to duodenum) Fever/Febrile, Tachycardia (part of inflammatory response and cytokine release) - may have unstable BP Marked abdominal tenderness

Question 33

Acute pancreatitis Diagnosis

Answer 33

1. Clinical symptoms and signs (not particularily specific) 2. High WBC cell count (neutrophil leukocytose - increase in acute inflammatory response cells). Still not specific for acute pancreatitis. (could also be seen in acute cholecistisis) 3. Elevated serum amylase and lipase - useful - enzymes released from pancreatic acinar cells - not specific for acute pancreatitis. Cholecystitis and gastritis may have mild elevation - often not to same extent as acute pancreatitis 4. CT scan abdomen - oedema, necrosis, pseudocysts of the pancreas 5. Rarely may need laparotomy to confirm diagnosis - abdominal surgery, perforated viscous or acute surgical problem. Less common due to imaging and lab investigations

Question 34

Acute Pancreatitis Management

Answer 34

"Rest the pancreas" - inflammatory process settle down, so reduce stimulation of pancreas (reduce pancreatic enzyme release) - not eating food by mouth- so not stimulating pancreatic enzymes 1. IV fluids 2. NG suction (remove gastric and duodenal secretions) 3. Analgesia(often quite significant) (fluid replacement) 4. Close monitoring (for complications)

Question 35

Chronic Pancreatitis

Answer 35

Defined as: "Repeated bouts of pancreatic inflammation with loss of pancreatic parenchyma and replacement of fibrosis tissue" Microscopic difference to acute P: -see more chronic inflammatory cells(macrophages) + repair mechanism of fibrosis and scarring -Majority have heavy alcohol intake 60-70%

Question 36

Pathology of Chronic Pancreatitis

Answer 36

Fibrotic organ: can be rock hard Atrophy of the exocrine component but relative sparing of the islets -if ongoing can affect function of pancreas, tends to effect for exocrine components- lead to malabsorption problems (rather than endocrine). Therefore unusual to see Diabetes as a complication of chronic pancreatitis. Mild chronic inflammatory infiltrate Calcification (seen in CT scan)

Question 37

Clinical features of Chronic Pancreatitis

Answer 37

Repeated attacks of abdominal pain -often bought on by alcohol (sometimes clinically difficult to sort out. as person with heavy alcohol intake may also have alcoholic hepatitis- cause liver disfunction and upper abdominal pain) -can also have gastritis and gastric ulceration Can be more persistent pain If ongoing: 1. Loss of exocrine function (malabsorption) 2. Pseudocysts (scarring and cavity formation/pseudocyts -seen on imaging) 3. Rarely diabetes mellitus -if have repeated episodes Serum Amylase levels may not be as useful (less dramatic rises)

Question 38

Pancreatic Carcinoma

Answer 38

4th most common cause of cancer death Males slightly more > Female Most aged > over 50 (peak 60-80) Prognosis remains poor (

Question 39

Pancreatic Carcinoma: Risk factors/associations

Answer 39

- Tobacco smoking - Heavy alcohol intake - High BMI - coffee drinking as well - carcinogenic or lifestyle associations

Question 40

Pancreatic Carcinoma: Pathology

Answer 40

Pathology: Adenocarcinoma -tumours: epithelial and form glandular structures 60-70% head (majority) -invade Ampulla, biliary obstruction (common bile duct) (jaundice, pale stool, dark urine) 5-10% body 10-15% tail -Body and Tail: remain silent, often large and disseminated at presentation, spread to nodes, adjacent organs, liver, bones, lungs (silent, late in presentation as consequence to anatomical site) 20% diffuse -throughout pancreas

Question 41

Pancreatic Carcinoma Clinical Features

Answer 41

``` Obstructive Jaundice Pain (invading adjacent structures/head of pancreas around duodenum) Weight loss (malignancy possibility) Pancreatitis (obstructing pancreatic duct/(commonly from gall stone or alcohol) Thrombophlebitis/Venous thrombosis -spontaneous clot formation, often in deep veins of legs. Long distance flying, immobile, come off plane and have swollen, painful leg. Scanned and have clot in leg. -Risk: can break off and embolyse the lung (pulmonary embolisms) -anyone with cancer have higher risk of veinous thrombosis (pancreatic cancer has very high incidence of venous thrombosis, and variation of thrombophlebitis -superficial veins (of lower limbs esp.) clotted/thrombosed and associated inflammation around veins (assoc. with hypercoaguability of patients with malignancy/pancreatic cancer) ```

Question 42

Patient with Jaundice

Answer 42

Hepatobiliary pathology - age of malignancy - pot. tumour in pancreas head causing obstruction - pot. gallbladder pathology, with cholilothiasis shedding stones into common bile duct

Question 43

Clinical features of Pancreatic Carcinoma

Answer 43

Diagnosis usually suspected on imaging | Confirmed by CT (usually) or US guided FNA and core biopsy or open biopsy at laparotomy

Question 44

Pancreatic Endocrine Tumours

Answer 44

Islet cell tumours - rare - may secrete pancreatic hormones (insulin) - e.g. insulinoma 1. Hypoglycaemia 2. Most benign, 10% malignant 3. Treat with resection (stop hypoglycaemia)