digestive system 5 - … · digestive system 5 lecture 15 pathology and clinical ... histology from...

Digestive System 5

Lecture 15

Pathology and Clinical

Science 1 (BIOC211)

Department of BioscienceText Reference:

Grossman, S.C. & Porth, C.M. (2014). Porth’s Pathophysiology: concepts of

altered health states, (9th ed.). Philadelphia, U.S.A. Walters Kluwer Health -

Lippincott, Williams & Wilkins.

© endeavour.edu.au

© Endeavour College of Natural Health endeavour.edu.au 2

SESSION LEARNING OBJECTIVES

This session aims to:

o Understand the use of various diagnostic tests and

procedures for liver and biliary disorders

o Comprehend how and why the symptoms and signs of

liver disorder appear

o Describe the aetiology, pathology and principles of

treatment for common and important disorder of the liver

and biliary tract


DISEASES OF THE LIVER AND

BILIARY TRACTo Investigation of liver disease

o Clinical features and presentations of liver disease

o Liver diseases

• Chronic liver disease

• Viral hepatitis

• Alcoholic liver disease

• Hepatocellular carcinoma

o The gall bladder and biliary system

• Gall stones

• Cholecystitis


THE LIVER AND BILIARY TRACT

From Principles of Anatomy and Physiology. (12th ed.,p. 943), by Tortora G & Derrickson B. 2009.

Hoboken, NJ. John Wiley and Sons.


THE LIVER - HISTOLOGY

From Principles of Anatomy and Physiology. (12th ed.,p. 943), by Tortora G & Derrickson B. 2009.

Hoboken, NJ. John Wiley and Sons.


THE LIVER AND BILIARY TRACT

From Principles of Anatomy and Physiology. (12th ed.,p. 943), by Tortora G & Derrickson

B. 2009. Hoboken, NJ. John Wiley and Sons.


INVESTIGATION OF LIVER

DISEASEo Liver function tests used to assess liver disease

• Bilirubin

• Aminotransferases ( Alanine Aminotransferase [ALT],

Aspartate Aminotransferase [AST])

• Alkaline phosphatase

• Gamma glutamyl transferase ( GGT )

• Albumin

o Tests to determine severity and activity of liver disease

• Biochemical tests ( Liver Function Tests [LFTs] )

• Coagulation tests


INVESTIGATION OF LIVER

DISEASE

o Imaging

• Ultrasound

• CT Scan

• Magnetic Resonance Imaging (MRI)

• Endoscopic Retrograde

Cholangiopancreatography (ERCP)

o Liver biopsy


PRIMARY LIVER CANCER

http://brighamrad.harvard.edu/Cases/bwh/images/335/ct2.jpg


CLINICAL FEATURES &

PRESENTATIONS OF LIVER

DISEASE• Asymptomatic abnormal liver function tests

• Jaundice

• Gastrointestinal bleeding

• Ascites

• Hepatic encephalopathy

• Haematologic disorders

• Endocrine / Neurological disorders

• Skin disorders


JAUNDICEo Definition

• Yellow appearance of skin, sclerae and mucous membranes

produced by increased bilirubin in body fluids

• Clinically detected when bilirubin >50μmol/L

o Classification

• Pre-hepatic - Haemolytic

• Intra-hepatic - Hepatocellular

• Post-hepatic - Cholestatic

• Neonatal hyperbilirubinaemia

o Pathophysiology

• varied

o Causes

• Depend on types


TYPES OF JAUNDICE

From Pathophysiology for Health Professions. (2nd ed), by Gould B. 2002. Philadelphia. W B

Saunders Company


CAUSES & EFFECTS OF LIVER INJURY

Liver Cell Injury

Viruses Chemicals

Alcohol Drugs

Cell necrosis

Mixed cell reactions

Fatty changes

Jenny Yeeles


ACUTE LIVER FAILUREo Definition

• Hepatic encephalopathy results from a sudden

severe impairment of hepatic function

o Aetiology

• Any cause of liver damage

• Due to acute viral hepatitis most common

o Epidemiology

• Uncommon

o Pathophysiology:

• Necrosis of substantial part of liver


CHRONIC LIVER FAILURE

o Functional capacity of the liver can no longer

maintain normal physiological condition

o The most common cause is cirrhosis

o Clinical Features

• Worsening liver function

• Jaundice

• Portal hypertension


• Ascites


LIVER FAILURE

From Porth’s Pathophysiology: concepts of altered health states, (9th ed., p. 1232)

by Grossman, S.C. & Porth, C.M. (2014). Philadelphia, U.S.A. Walters Kluwer

Health - Lippincott, Williams & Wilkins.


CIRRHOSISDefinition

o Necrosis of liver cells followed by fibrosis & nodule

formation causing abnormal liver architecture interfering

with normal liver blood flow & function

Causes

o World-wide, the most common causes are viral hepatitis

and prolonged excessive alcohol consumption

o Prolonged biliary damage or obstruction

Pathophysiology

o Chronic injury causing inflammation and fibrosis

o Loss of normal liver architecture

o Micronodular and Macronodular


CIRRHOSIS

Gould B. Pathophysiology for Health Professions. 2nd edition 2002. W B Saunders Company


CIRRHOSIS

http://images.paraorkut.com/img/health/images/c/cirrhosis-931.jpg


CIRRHOSISClinical Features

• Hepatomegaly

• Jaundice

• Ascites

• Endocrine changes

• Circulatory changes

• Haemorrhagic tendency

• Portal hypertension


Investigations

o Refer back to investigations of liver


ASCITES

http://meded.ucsd.edu/clinicalimg/abdomen_ascites5.jp http://byebyedoctor.com/wp-content/uploads/2011/08/ascites.jpg


CIRRHOSIS

Management

o Managing the complications

o Maintenance of nutrition

o Early detection of Hepatocellular Ca

o Avoid alcohol

o Liver transplant

Prognosis

o Overall poor, 5 year survival 50%

Differential Diagnosis

o Jaundice, causes as above


CLINICAL FEATURES OF CIRRHOSIS





PORTAL HYPERTENSION

Characterized by prolonged elevation of portal venous pressure

Aetiology

90% due to cirrhosis

Pathogenesis

Increased portal vascular resistance and development of collateral vessel formation particularly in the GIT

o Clinical features

• Splenomegaly (hypersplenism and thrombocytopenia)

• GIT bleeding from collateral vessels


PORTAL HYPERTENSION


VIRAL HEPATITISCommon cause of jaundice

o Causes

• Common ( hepatitis A, B, C, E and D viruses )

• Less common ( cytomegalovirus, E-B virus )

o Epidemiology

• HAV = commonest, outbreaks, faeco-oral spread

• HBV = 300M carriers, spread by IV or close body

contact

• HCV = 240M infected, blood transfusion, IV spread

o Pathophysiology

• Necrosis of hepatocytes – degree depends on persons

immune response


VIRAL HEPATITIS

o Clinical Features

• Non-specific prodromal symptoms

• Jaundice

• Vomiting, diarrhoea, abdominal discomfort

• Dark urine and pale stools

o Investigations

• LFTs

• Specific markers


VIRAL HEPATITIS

o Treatment

• Supportive

• Prevention (vaccine = HAV, HBV)

• Medical (interferon for HVB and HBC)

o Prognosis & Natural Progression:

• Depends on cause

• HAV = excellent, most recover, no Chronic Liver

Disease (CLD)

• HBV = most recover completely, 5- 10% CLD +

Hepatocellular Ca, asymptomatic carriers

• HCV = develop CLD, cirrhosis, hepatocellular Ca


COURSE

OF

HEPATITIS B


ALCOHOLIC LIVER DISEASEo Epidemiology

• 10% of alcoholics develop liver disease

o Pathophysiology

• Mechanism poorly understood

• Cirrhosis

o Clinical features

• Fatty liver

• Hepatitis

• Cirrhosis

o Investigations

• LFTs

o Management

• Abstinence and Management of complication


STEATOSIS - FATTY LIVER

http://www.livercare.com.au/Image/fattyliv.jpg

http://topnews.in/health/files/liver-5.jpg

http://www.123rf.com/photo_6530607_fatty-liver.html

Fatty Liver – external view

Fatty Liver – cross section

Fatty Liver – Histology


NON-ALCOHOLIC FATTY LIVER

DISEASEo Disease of affluent societies due to rise in obesity

o Most common cause of chronic liver disease after VH

and alcohol

o Epidemiology

• 3% of population in USA, prevalence higher in diabetes

and metabolic syndrome

o Pathophysiology

• First hit ( increased fat import ) → steatosis ( fatty liver )

• Second hit ( production of toxin ) → inflammation &

fibrosis


NON-ALCOHOLIC FATTY LIVER

DISEASE

o Clinical features:

• Abnormal liver function tests

o Management:

• Reduce BMI and insulin resistance

o Prognosis

• Depends +/- cirrhosis

• 10% - 15% of people will progress to cirrhosis


INHERITED LIVER DISEASES

o Hemochromatosis

• Iron is deposited throughout the body

especially liver, pancreas, heart

• Autosomal recessive disorder

• Acquired

o Wilson’s disease ( hepatocellular

degeneration )

• Excess copper deposited causing damage to

several organs

• Autosomal recessive disorder


http://www.pnas.org/content/97/23/12770/F2.expansion.html

A. Hyperplastic

nodule

B. Iron stain displays

iron granules

C. Nodules within

bridging fibrosis

D. Fibrosis and

inflammation

E. Intracellular

deposition of

copper

F. Hyperplastic

nodules


HEPATOCELLULAR CARCINOMA

o Epidemiology

• Most common primary liver tumour – 2.5-5/ 100,000

• Commoner in SE Asia – 40/ 100,000

o Aetiology

• Chronic hepatitis B infection

• Cirrhosis

• The risk is higher in men and rises with age

o Clinical features

• Asymptomatic

• Features of underlying chronic liver disease


HEPATOCELLULAR CARCINOMA

http://www.humpath.com/IMG/jpg_cirrhosis_alagille_hepatocellular_carcinoma_2801_2-3.jpg


HEPATOCELLULAR CARCINOMAo Investigation

• Serum markers

• Ultrasound

• CT

• MRI

• Biopsy

o Management

• Surgery

• Transplant

• Chemo-embolization

• Largely palliative

o Prevention

• Prevention of hepatitis B


GALLSTONES Most common disorder of biliary tree

o Classification

• Cholesterol stones

• Pigment stones

• Mixed stones

o Epidemiology

• Overall prevalence 11% ( 18- 65 years ),Increases with age. Females more prone than males

o Causes

• Increased cholesterol secretion

• Impaired gallbladder emptying

o Clinical Features

• Mostly asymptomatic

• Biliary Colic

• Acute / chronic cholecystitis


GALLSTONES

http://medical-guides.com/wp-content/uploads/2009/01/gallstones.jpg

http://marilynbrooksonmedicine.com/wp-

content/uploads/2010/10/gallbladder.jpg


GALLSTONES

From Porth’s Pathophysiology: concepts of altered health states, (9th ed., p. 1236) by

Grossman, S.C. & Porth, C.M. (2014). Philadelphia, U.S.A. Walters Kluwer Health -

Lippincott, Williams & Wilkins.


CHOLELITHIASIS – GALL STONES

http://www.ourwebdoctor.com/images/gallstn.jpg


GALLSTONES o Investigations

• Plain X-ray

• Ultrasound

• Cholecystography

• CT

o Complications

• Mucocele, empyema, migration to common bile duct (CBD

Treatment

• Surgery (Cholecystectomy if symptomatic)

• Lithotripsy

• Oral bile acids

o Differential Diagnosis

• Acute pancreatitis

• Differential Diagnosis of RUQ pain


CHOLECYSTITIS

Acute cholecystitis is almost always associated

with obstruction of gallbladder neck or cystic

duct by gallstone

o Clinical features

• Pain in RUQ/ epigastrium ( severe and

prolonged )

• Fever and leucocytosis

o Management

• Bed rest, pain relief, antibiotics

• Surgery


Readings and ResourcesResources:

o Set Textbooks:

Colledge, N.R., Walker, B.R. & Ralston S.H. (2014). Davidson’s Principles and Practice of Medicine, (22nd ed.). Edinburgh.

Churchill Livingstone.

Grossman, S.C. & Porth, C.M. (2014). Porth’s Pathophysiology: concepts of altered health states, (9th ed.). Philadelphia,

U.S.A. Walters Kluwer Health - Lippincott, Williams & Wilkins.

o Additional textbooks:

Davies, A. & Moores, C. (2010). The respiratory system: basic science and clinical conditions, (2nd ed.). Edinburgh. Churchill,

Livingstone, Elsevier.

Field, M., Pollock, C., Harris, D. (2010). Systems of the Body: The Renal System; Basic Science and Clinical Conditions. (2nd

ed.). United Kingdom: Churchill Livingstone.

Jamison, J.R. (2006) Differential Diagnosis for Primary Care: a handbook for health care practitioners. (2nd ed.). Edinburgh.

Churchill Livingstone.

Lee, G. & Bishop, P. (2013). Microbiology and Infection Control for Health Professionals, (5th ed.). Frenchs Forest, NSW.

Pearson Education.

McCance, K.L. & Huether, S.E. (2014). Pathophysiology: the biological basis for disease in adults and children, (7th ed.). St.

Louis, MO. Elsevier.

Murphy, K. (2011). Janeway’s immunobiology, (8th ed.). New York. Garland Science.

Noble, A., Johnson, R. & Bass, P. (2010). The cardiovascular system: basic science and clinical conditions, (2nd ed.).

Edinburgh. Churchill, Livingstone, Elsevier.

Pagana, K.D. & Pagana, T.J. (2013). Mosby’s diagnostic and laboratory test reference, (11th ed.). St. Louis, MO. Elsevier.

Smith, M.E. & Morton, D.G. (2010). The digestive system: basic science and clinical conditions, (2nd ed.). Edinburgh.

Churchill, Livingstone, Elsevier.

VanMeter, K.C. & Hubert, R. (2014). Gould’s pathophysiology for health professions, (5th ed.). St. Louis, MO. Elsevier.


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