Lect 8 Liver Disease

8/3/2019 Lect 8 Liver Disease

1/76

Pathology ofPathology ofHepatitis & CirrhosisHepatitis & Cirrhosis

SMS 2044


2/76

Normal Liver


3/76

The Liver

The right upper quadrant of the abdomen isdominated by the liver and its companion

biliary tree and gallbladder.

Residing at the crossroads between thedigestive tract and the rest of the body, the

liver has the enormous task of maintaining thebody's metabolic homeostasis.


4/76

Autopsy

1.5 kg, wedge shape

4 lobes, Right, left,

Caudate, Quadrate.

Double blood supply

Hepatic arteries

Portal Venous blood

Acini / Portal triad.

Lobules central. V


5/76

Normal Liver - Infant


6/76

CT Upper abdomen - Normal


7/76


8/76

N

OFIBROUS

TISSUE

Normal Liver - Microscopy


9/76


10/76

Liver Functions:

Metabolism Carbohydrate, Fat & Protein

Secretory bile, Bile acids, salts & pigments

Excretory Bilirubin, drugs, toxins

Synthesis Albumin, coagulation factors

Storage Vitamins, carbohydrates etc.Detoxification toxins, ammonia, etc.


11/76

GENERAL PRINCIPLES

The liver is vulnerable to a wide variety of metabolic,toxic, microbial, and circulatory insults.

In some instances, the disease process is primary to theliver. In others, the hepatic involvement is secondary,

often to some of the most common diseases in humans,such as cardiac decompensation, alcoholism, and

extrahepatic infections.

However, with progression of diffuse disease or strategicdisruption of the circulation or bile flow,

the consequences of deranged liver function becomelife-threatening.


12/76


13/76


14/76FEATHERY DEGENERATION


15/76

Cell Death

Virtually any significant insult to theliver may causehepatocyte

destruction.

In necrosis, poorly stained mummified

hepatocytes remain, most commonly

as the result of ischemia (coagulative

necrosis).

Cell death that is toxic orimmunologically mediated occurs via

apoptosis, in which isolated

hepatocytes become shrunken,

pyknotic, and intensely

eosinophilic.


16/76

Alternatively, hepatocytes may osmotically swell and

rupture, so-called hydropic degeneration or lytic

necrosis.


17/76

In the setting of ischemia and a number

of drug and toxic reactions, hepatocyte

necrosis is distributed immediately

around the central vein (centrilobular

necrosis).

With more severe inflammatory or toxic

injury, apoptosis or necrosis of

contiguoushepatocytes may spanadjacent lobules in a portal-to-portal,

portal-to-central, or central-to-central

fashion (bridging necrosis).

Destruction of entire lobules(submassive necrosis) or most of the

liver parenchyma (massive necrosis) is

usually accompanied by hepatic failure.

With bacterial infection, macroscopicabscesses may occur.


18/76

Hepatitis:

Hepatitis: Inflammation of Liver

Viral, Alcohol, immune, Drugs & Toxins

Biliary obstruction gall stones.

Acute, Chronic & Fulminant - types

Viral Hepatitis

Specific Heptitis A, B, C, D, E, & other

Systemic - CMV, EBV, other.


19/76

Pattern of Viral Hepatitis:

Carrier state / Asymptomatic phase

Acute hepatitis

Chronic Hepatitis Chronic Persistent Hepatitis (CPH)

Chronic Active Hepatitis (CAH)

Fulminant hepatitis

Cirrhosis

Hepatocellular Carcinoma


20/76

Acute - Hepatitis - Chronic


21/76

Acute Hepatitis:

Swelling and Apoptosis

Piecemeal or Bridging, panacinar necrosis

Inflammation lymphocytes, Macrophages

Ground glass hepatocytes HBV

Mild fatty change HCV

Portal inflammation and Cholestasis


22/76

Foreign bodies, organisms, and a variety of drugs may incite

a granulomatous reaction.


23/76

Signs and Symptoms

Abdominal pain

Joint and muscle pain

Change in bowel function Nausea, vomiting, anorexia

Lethargy, malaise

Fever (Hepatitis A)

Irritability


24/76

More Signs and Symptoms

oJaundice

oclay colored stools

odark urine

oPruritis/urticaria

oSkin abrasions

oRash


25/76

Fulminant Hepatitis:

Hepatic failure with in 2-3 weeks.

Reactivation of chronic or acute hepatitis

Massive necrosis, shrinkage, wrinkled

Collapsed reticulin network

Only portal tracts visible

Little or massive inflammation time

More than a week regenerative activity

Complete recovery or - cirrhosis.


26/76

Chronic Hepatitis:

Persistent & Active types. CPH/CAH

Lymphoid aggregates

Periportal fibrosis

Necrosis with fibrosis bridging fibrosis.

Cirrhosis regenerating nodules.


27/76

Acute viral Hepatitis:


28/76



29/76



30/76

Acute viral Hepatitis C:


31/76

Liver Biopsy CPH:


32/76

Jaundice

Yellow discoloration of skin & sclera due toexcess serum bilirubin. >than 85 umol/l

(5 mg/dL)

Conjugated & Unconjugated types

Obstructive & Non Obstructive (clinical)

Pre-Hepatic, Hepatic & Post Hepatic types

Jaundice - Not necessarily liver disease *


33/76

Hepatic bile formation serves two major functions.Bile constitutes the primary pathway for the elimination of

bilirubin, excess cholesterol, and xenobiotics that areinsufficiently water soluble to be excreted into urine.

Second, secreted bile salts and phospholipid moleculespromote emulsification of dietary fat in the lumen of thegut.

Thus, jaundice, a yellow discoloration of skin and sclerae(icterus), occurs when systemic retention of bilirubin

leads to elevated serum levels above 2.0 mg/dL, thenormal in the adult being less than 1.2 mg/dL.

Cholestasis,is defined as systemic retention of not onlybilirubin but also other solutes eliminated in bile(particularly bile salts and cholesterol).

Jaundice


34/76

Common Causes of Jaundice

Pre Hepatic (Acholuric) - Hemolytic

Unconjugated/Indirect Bil, pale urine

Hepatic Viral, alcohol, toxins, drugs

Liver damage - unconjugated

Swelling, canalicular obstruction - Conjugated

Post Hepatic (Obstructive) Stone, tumor

Conjugated/Direct Bil, High colored urine,


35/76

Normal bilirubin production (0.2 to

0.3 g/day) is derived primarily from

the breakdown of senescent

circulating erythrocytes, with a minor

contribution from degradation of

tissue heme-containing proteins.

Extrahepatic bilirubin is bound to

serum albumin and delivered to the

liver.

Bilirubin metabolism and

elimination.

Hepatocellular uptake andglucuronidation by glucuronosyltransferase in the

hepatocytes generates bilirubin which are water

soluble and readily excreted into bile.


36/76

Gut bacteria deconjugate the bilirubin and degrade it to

colorless urobilinogens.

The urobilinogens and the residue of intact pigments areexcreted in the feces, with some reabsorption and re-

excretion into bile.


37/76

PATHOPHYSIOLOGY OFJAUNDICE

Both un-conjugated bilirubin and

bilirubin glucuronides may accumulate

systemically and deposit in tissues,

giving rise to the yellow discoloration of

jaundice.

This is particularly evident in the

yellowing of the sclerae (icterus).

There are two important pathophysiologic differences

between the two forms of bilirubin.

Un-conjugated bilirubin is tightly complexed to serum

albumin and is virtually insoluble in water at physiologic pH.


38/76


39/76

This form cannot be excreted inthe urine even when blood levels

are high.

Normally, a very small amount

of unconjugated bilirubin is

present as an albumin-free

anion in plasma.

The unbound plasma fractionmay increase in severe

hemolytic disease or when

protein-binding drugs displace

bilirubin from albumin.

I t t j t d bili bi i


40/76

In contrast, conjugated bilirubin is

water soluble, nontoxic, and only

loosely bound to albumin.

Because of its solubility and weakassociation with albumin, excess

conjugated bilirubin in plasma can

be excreted in urine.

With prolonged conjugated

hyperbilirubinemia, a portion of

circulating pigment may become

covalently bound to albumin.

This "delta fraction" may persist in

the circulation for weeks after

correction of a cholestatic insult,

owing to the plasma lifetime of

albumin.

In the normal adult serum bilirubin levels vary between 0 3 and 1 2


41/76

In the normal adult, serum bilirubin levels vary between 0.3 and 1.2mg/dL

Jaundice becomes evident when the serum bilirubin levels riseabove 2.0 to 2.5 mg/dL; levels as high as 30 to 40 mg/dL can occur

with severe disease.

Jaundice occurs when the equilibrium between bilirubin productionand clearance is disturbed by one or more of the following

mechanisms:

(1) excessive production of bilirubin, (2) reduced hepatic uptake,

(3) impaired conjugation, (4) decreased hepatocellular excretion,and

(5) impaired bile flow (both intrahepatic and extrahepatic).

The first three mechanisms produce unconjugatedhyperbilirubinemia, and the latter two produce predominantly

conjugated hyperbilirubinemia.


42/76

The morphologic alterations that cause liver failure fall into

three categories:

1. Massive hepatic necrosis. This is most often caused by

fulminant viral hepatitis (hepatotropic or nonhepatotropic

viruses).

Drugs and chemicals also may induce massive necrosis

1.Chronic liver disease. This is the most common route tohepatic failure and is the end point of relentless chronic liver

damage ending in:

2. Cirrhosis.

Clinical Features


43/76

Clinical Features

Jaundice is an almost invariable finding.

Impaired hepatic synthesis and secretion of albumin leadsto hypoalbuminemia, which predisposes to peripheral edema.

Hyperammonemia is attributable to defective hepatic urea

cycle function.

Fetor hepaticus is a characteristic body odor variously

described as "musty" or "sweet and sour" and occurs

occasionally.


44/76

A coagulopathy develops, attributable to impaired hepaticsynthesis of blood clotting factors II, VII, IX, and X.

The resultant bleeding tendency may lead to massive

gastrointestinal hemorrhage as well as petechial bleeding

elsewhere.

Hepatic encephalopathy

Hepatic encephalopathy is a feared complication of acute

and chronic liver failure


45/76

Cirrhosis


46/76

Cirrhosis

Fibrosis

Regenerating Nodule


47/76

CIRRHOSIS, TRICHROME STAIN

f C


48/76

Etiology of Cirrhosis

Alcoholic liver disease 60-70%

Viral hepatitis 10%

Biliary disease 5-10%

Primary hemochromatosis 5%

Cryptogenic cirrhosis 10-15%

Wilsons, 1AT def rare


49/76

Pathogenesis:

Hepatocyte injury leading to necrosis. Alcohol, virus, drugs, toxins, genetic etc..

Chronic inflammation - (hepatitis).

Bridging fibrosis.

Regeneration of remaining hepatocytes

Proliferate as round nodules.

Loss of vascular arrangement results in

regenerating hepatocytes ineffective.


50/76

Cirrhosis Features:

Liver Failure

Parenchymal regeneration but why ..??.

Portal obstruction, Porta systemic shunts

Portal hypertension, Splenomegaly

Jaundice, Coagulopathy, hypoproteinemia,

toxemia, Encephalopathy,


51/76

Micronodular cirrhosis

A iti i Ci h i


52/76

Ascitis in Cirrhosis

A iti i Ci h i


53/76

Ascitis in Cirrhosis


54/76

Micronodular cirrhosis:


55/76

Macronodular Cirrhosis

Li Bi Ci h i


56/76

Liver Biopsy Cirrhosis

Li Bi Ci h i


57/76

Liver Biopsy Cirrhosis:


58/76

Nutmeg Liver-Cardiac Sclerosis

Cli i l F t


59/76

Clinical Features

Hepatocellular failure. Malnutrition, low albumin & clotting factors,

bleeding.

Hepatic encephalopathy.

Portal hypertension.

Ascites, Porta systemic shunts, varices,

splenomegaly.


60/76

CirrhosisClinical

Features

Gynaecomastia in cirrhosis


61/76

Gynaecomastia in cirrhosis

Porta-systemic anastomosis:


62/76

Porta systemic anastomosis:Prominent abdominal veins.


63/76

MRI Cirrhosis

Complications:


64/76

Complications:

Congestive splenomegaly.

Bleeding varices.

Hepatocellular failure.

Hepatic encephalitis / hepatic coma.

Hepatocellular carcinoma.

Alcoholic Liver Injury:


65/76

Alcoholic Liver Injury:

Ethyl alcohol : Common cause ofacute/Chronic liver disease

Alcoholic Liver disease - Patterns

Fatty change,

Acute hepatitis (Mallory Hyalin)

Chronic hepatitis with Portal fibrosis

Cirrhosis, Chronic Liver failure

All reversible except cirrhosis stage.

Alcoholic Liver Injury: Pathogenesis


66/76

Alcoholic Liver Injury: Pathogenesis

Acetaldehyde metabolite hepatotoxicDiversion of metabolism fat storage.

Oxidation of ethanol NAD to NADH. NAD is

required for the oxidation of fat..

Increased peripheral release of fatty acids.

Inflammation, Portal bridging fibrosis

Stimulates collagen synthesis fibrosis.

Micronodular cirrhosis.

Alcoholic Liver Damage


67/76

Alcoholic Liver Damage


68/76

Alcoholic Fatty Liver


69/76




70/76


Alcoholic Hepatitis


71/76

Alcoholic Hepatitis

Normal Liver Histology


72/76

Normal Liver Histology

CV

PT

f


73/76

BRAIN

LIVER

Toxic N2 metabolites

From Intestines

Porta systemic

shunts

Pathogenesis of Hepatic Encephalopathy

Bleeding in Liver disease:


74/76

Bleeding in Liver disease:

vitamin K in livergamma-carboxyglutamicacid for coagulation factors II, VII, IX, and X.

Liver disease factor VII is the first to go

so the defect will appear initially in theextrinsic pathway, i.e., abnormal PT. When

severe it affects both pathways.

Conclusions:


75/76

Conclusions:

Common end result of diffuse liver damage.(Viral hepatitis, Alcohol, congenital, drugs, toxins & Idiopathic)

Characterised by diffuse loss of architecture.

Fibrous bands & regenerating nodules distortand abstruct blood flow. (inefficient function)

Hepatocellular insufficiency & portal

hypertension.Shrunken, scarred liver, ascitis,

spleenomegaly, liver failure, CNS toxicity.

Prevention Teaching


76/76

Prevention Teaching

What would you teach?

Adequate sanitation andhygiene

Wash hands before eatingand after using the toilet

Drink only purified or bottledwater

No sharing of eating utensils,needles, toothbrushes,razors, etc.

Use a

Lect 8 Liver Disease

Documents

Transcript of Lect 8 Liver Disease