I, caudate lobe; II-IV the I, caudate lobe; II-IV the left-; V-VIII the right left-; V-VIII the right hemiliverhemiliver

Functional unit: Functional unit: acinus acinus PT: PT: PV, arteriole, bile PV, arteriole, bile

ductuleductuleZone 1 Zone 1 is well O2; more is well O2; more resistant than zone 3. resistant than zone 3.

Sinusoids Sinusoids lack BM; have lack BM; have fenestrated endoth. & fenestrated endoth. &

Kupffer cells. Bile Kupffer cells. Bile canaliculi join to form canaliculi join to form

bile ductulesbile ductules

BM: basement membrane

THV: terminal hepatic venule

PT: Portal triad

Cirrhosis & Portal Cirrhosis & Portal HypertensionHypertension

At the end we will learnAt the end we will learn

CLD is rare in children (1/5000)CLD is rare in children (1/5000) CLD may be CLD may be idiopathicidiopathic Most CLD are preventableMost CLD are preventable Commonest c/of PH is cirrhosisCommonest c/of PH is cirrhosis Commonest c/of HCC is HBVCommonest c/of HCC is HBV HCV is curableHCV is curable

CLD: chr. liver d. PH: portal HTN. HCC: HC CaCLD: chr. liver d. PH: portal HTN. HCC: HC Ca

DefinitionDefinitionChr. liver d.: Chr. liver d.: progressive destruction & regen. of progressive destruction & regen. of

Liver parenchyma lasting Liver parenchyma lasting >6mo >6mo leading to cirrhosis. leading to cirrhosis. It includes: It includes: inf., metabolic, genetic, drugs, idiopathic, ., metabolic, genetic, drugs, idiopathic,

structural, HCC & AIDstructural, HCC & AID

Cirrhosis: Cirrhosis: scarring of Liver from injury/long-term d. scarring of Liver from injury/long-term d. blocking BF: blocking BF: HC failure & HC failure &

Portal HTN developPortal HTN develop Chr. Hepatitis: Chr. Hepatitis: chr. inflamchr. inflam

within L. leading to cirrhosiswithin L. leading to cirrhosis& liver failure; persistent & liver failure; persistent for a period of 6mofor a period of 6mo

BF: blood flow. D: disorder/diseaseBF: blood flow. D: disorder/disease

Etiology of Cirrhosis & PHEtiology of Cirrhosis & PH

Infections: Infections: Liver disorders: Liver disorders: Bile ductal blockages: Bile ductal blockages: Drugs & toxins: Drugs & toxins:

Liver disorders:Liver disorders: – Autoimmune hepatitis:Autoimmune hepatitis:– Chr. Chr. alcoholismalcoholism– Hereditary:Hereditary:

HemochromatosisHemochromatosis αα1-antitrypsin deficiency1-antitrypsin deficiency GSDGSD GalactosemiaGalactosemia CFCF Fructose intoleranceFructose intolerance TyrosinemiaTyrosinemia Wilson DWilson D

– Indian childhood cirrhosisIndian childhood cirrhosis

Autoimmune Liver DiseasesAutoimmune Liver DiseasesProgressive inflam. by autoantibodies; rare in children: Progressive inflam. by autoantibodies; rare in children: 2% 2% of LD in specialized pediatric L. centersof LD in specialized pediatric L. centersBroad clinical spectrum. Broad clinical spectrum. Quickly responds to steroids Quickly responds to steroids

& immunosuppressants& immunosuppressantsCommon Common SS: SS: tiredness & unwellness, anorexia, school tiredness & unwellness, anorexia, school deterioration. deterioration. HSM, abnormal LFT, HSM, abnormal LFT, autoantibodiesautoantibodies, , characteristic liver characteristic liver biopsybiopsy

Dx Dx is often by is often by exclusionexclusion. Anti-sm Ab, anti-liver kidney . Anti-sm Ab, anti-liver kidney microsome type I Ab, ANA. Biopsy may be necessary microsome type I Ab, ANA. Biopsy may be necessary for for type & severity of L. damage & inflamtype & severity of L. damage & inflam2 types: 2 types: AIH & AI sclerosing cholangitisAIH & AI sclerosing cholangitis

Inherited liver diseasesInherited liver diseases

>100 liver diseases; >100 liver diseases; some are inherited. 2 common are some are inherited. 2 common are haemochromatosis & alpha-1 antitrypsin d.haemochromatosis & alpha-1 antitrypsin d.

Haemochromatosis: Haemochromatosis: excess Fe is absorbed & deposited. The excess Fe is absorbed & deposited. The commonest is hereditary. 2y HC occurs in hemolytic a. commonest is hereditary. 2y HC occurs in hemolytic a. Genetic HC affects M x5. As F menstruate, are unlikely Genetic HC affects M x5. As F menstruate, are unlikely to show SS till >10y after MP. to show SS till >10y after MP. More in N Europe More in N Europe

SS: SS: Hepatomegaly, joint p, fatigue, unexplained wt loss, Hepatomegaly, joint p, fatigue, unexplained wt loss, darkening of skin ("bronzing“), AP, loss of libido. DM darkening of skin ("bronzing“), AP, loss of libido. DM & & heart d. may dev.; also cirrhosis, HCC, testicular heart d. may dev.; also cirrhosis, HCC, testicular atrophy, & chr AP. Blood iron is confirmatory. HC DNA atrophy, & chr AP. Blood iron is confirmatory. HC DNA test is done; also for screeningtest is done; also for screening

Rx.Rx. of haemochromatosis of haemochromatosis

to remove excess Fe, reduce SS or complications. Fe is to remove excess Fe, reduce SS or complications. Fe is removed by phlebotomy: ½L blood is removed/w for 2-3y removed by phlebotomy: ½L blood is removed/w for 2-3y

until Fe is reduced; then less frequently: based on until Fe is reduced; then less frequently: based on individual circumstancesindividual circumstances

Avoid dietary Fe, most commonly offal, red meat & Avoid dietary Fe, most commonly offal, red meat & fortified BF cereals, also multi-vitamin prepn.fortified BF cereals, also multi-vitamin prepn.

It is also a good idea to limit It is also a good idea to limit vitamin Cvitamin C No alcoholNo alcohol

If HC has caused cirrhosis, the risk of HCC is higher. As a If HC has caused cirrhosis, the risk of HCC is higher. As a result, screening should be performed/6moresult, screening should be performed/6mo

Alpha-1 antitrypsin d.Alpha-1 antitrypsin d.

an imp. Liver protein alpha-1 antitrypsin, an imp. Liver protein alpha-1 antitrypsin, is either lacking or is either lacking or low. Pts. are able to make it; but, the disease low. Pts. are able to make it; but, the disease

prevents prevents it from entering blood & accumulates in liverit from entering blood & accumulates in liver A1AT protects lungs from damage. A1AT protects lungs from damage. The d. causes the lungs The d. causes the lungs

become damaged: difficulty breathingbecome damaged: difficulty breathing 1% COPD have A1AT deficiency. Risk of cirrhosis is high 1% COPD have A1AT deficiency. Risk of cirrhosis is high

SS: SS: first symptoms appear usually in lungs: COPD: first symptoms appear usually in lungs: COPD: SoB/ SoB/ wheezing, unexplained wt loss & barrel-shaped chest wheezing, unexplained wt loss & barrel-shaped chest As it progresses, SS of cirrhosis may appear As it progresses, SS of cirrhosis may appear

A1AT in blood will confirm A1AT in blood will confirm

Rx.: Rx.: No cure. Replacement has been triedNo cure. Replacement has been tried

Rx COPD & cirrhosis: ABT, inhaled medications. DiureticsRx COPD & cirrhosis: ABT, inhaled medications. Diuretics& other measures to reduce edema& other measures to reduce edema

No alcohol, smokingNo alcohol, smoking Healthy dietHealthy diet Flu & pneumonia vax.Flu & pneumonia vax. Treat inf. Treat inf. asapasap. Occasionally the lungs or liver deteriorate . Occasionally the lungs or liver deteriorate

despite Rx. Lung/liver transplant may be neededdespite Rx. Lung/liver transplant may be needed With appropriate Rx A1AT is usually not fatal. But, With appropriate Rx A1AT is usually not fatal. But,

complications a/with them can be fatalcomplications a/with them can be fatal It is v. imp. that people with inherited LD do all they can It is v. imp. that people with inherited LD do all they can

to stay healthyto stay healthy

Bile ductal blockagesBile ductal blockages

– Cong.: biliary atresia Cong.: biliary atresia – Sclerosing cholangitis– Gallbladder surgeryGallbladder surgery

Drugs & toxinsDrugs & toxins– Paracetamol. arsenic, INH Paracetamol. arsenic, INH – MethotrexateMethotrexate– Excess vitamin A, ironExcess vitamin A, iron– Afla toxinAfla toxin

InfectionsInfections– Hepatitis B, C, DHepatitis B, C, D– Schistosomiasis, BrucellosisSchistosomiasis, Brucellosis– Echinococcosis, advanced or cong. syphilisEchinococcosis, advanced or cong. syphilis

Indian Childhood CirrhosisIndian Childhood Cirrhosis

a CLD of children (1–3y) due to deposition of Cu in liver. a CLD of children (1–3y) due to deposition of Cu in liver. It is It is a non-Wilsonian Cu overload by ingested Cu occurs a non-Wilsonian Cu overload by ingested Cu occurs

in in genetically susceptible infantsgenetically susceptible infants It had a v. high CFR before but has eventually become It had a v. high CFR before but has eventually become

preventable, treatablepreventable, treatable Now rareNow rare

CFR: case fatality rateCFR: case fatality rate

The commonest The commonest surgicalsurgical c/of cirrhosis in c/of cirrhosis in childhood is biliary atresiachildhood is biliary atresia

The commonest The commonest medicalmedical causes are causes are– infectionsinfections– alpha-1- antitrypsin Dalpha-1- antitrypsin D– metabolic LDmetabolic LD

C.F. of C.L.D.C.F. of C.L.D.Often asymptomatic in early! Often asymptomatic in early! Start with L. failure. Start with L. failure.

Severity depends on damageSeverity depends on damage– Early: Early: fatigue, weakness, AN, AP, fatigue, weakness, AN, AP, wt. losswt. loss– Later: Later: jaundice, jaundice, dark urinedark urine, itching, edema, ascites, , itching, edema, ascites,

poor healing, drug toxicity, testicular atrophy, poor healing, drug toxicity, testicular atrophy, poor poor hair, hair, hepatic facies, hepatic facies, easy bruising; esophageal, easy bruising; esophageal,

stomach & anal varices; stomach & anal varices; kidney failure, gall stoneskidney failure, gall stones

A small number get A small number get liver cancerliver cancer

CF have 2 componentsCF have 2 components

SS of Hepatocellular failureSS of Hepatocellular failure– pallor, edema, pallor, edema, fatigue, fatigue, jaundice,jaundice, itchy skin, dark urine, itchy skin, dark urine,

ANVANV, , wt. loss, palmar erythemawt. loss, palmar erythema– AP & swelling, pale stool, hepatic facies, spider nevi, AP & swelling, pale stool, hepatic facies, spider nevi,

pigmentationpigmentation– testicular atrophy, poor hair, gynecomazia, poor libidotesticular atrophy, poor hair, gynecomazia, poor libido

SS of Portal HypertensionSS of Portal Hypertension– ascites, distended vein (caput medusa), splenomegaly, ascites, distended vein (caput medusa), splenomegaly,

varices at PS junctions: hematemesis, varices at PS junctions: hematemesis, bloody/tar-bloody/tar-colored stoolcolored stool

Muehrcke's nails Muehrcke's nails

Terry’s nailsTerry’s nails

Kayser–Fleischer ring Kayser–Fleischer ring at limbus: deposition at limbus: deposition of Cu in Descemet m.: of Cu in Descemet m.: characteristic in most characteristic in most

neuro-Wilson& 50% of neuro-Wilson& 50% of hepatic WDhepatic WD

Arcus senilis

Mechanism of Ascites in CirrhosisMechanism of Ascites in Cirrhosis

Portal hypertension: Portal hypertension: commonestcommonest Hepatic arterial vasodilatationHepatic arterial vasodilatation HypoalbuminemiaHypoalbuminemia 2y hyperaldosteronism2y hyperaldosteronism Raised ADHRaised ADH

Complications of CirrhosisComplications of Cirrhosis

Palmar erythemaPalmar erythema HypogonadismHypogonadism Darkening of skinDarkening of skin GynecomaziaGynecomazia HypersplenismHypersplenism Spider neviSpider nevi Caput medusaCaput medusa Ascites, edemaAscites, edema

Varices: hgeVarices: hge Itching Itching Abdominal infx.Abdominal infx. EencephalopathyEencephalopathy Raised drug toxicityRaised drug toxicity Liver cancerLiver cancer

Spider naevi (arterial spider, vascular spider, naevus araneus, naevus

arachnoidius, spider angioma

DiagnosisDiagnosis

LFTLFT CT, USG, laparoscopy CT, USG, laparoscopy BiopsyBiopsy Others: Others:

– FibroscanFibroscan– Measuring the amount of caffeine in the salivaMeasuring the amount of caffeine in the saliva– Measuring the pressure within the liver vein Measuring the pressure within the liver vein – Ascitic fluid analysisAscitic fluid analysis

TreatmentTreatmentNothing cures scar tissue. Nothing cures scar tissue. Goals are:Goals are:

– Rx underlying causesRx underlying causes– Preventing further damagePreventing further damage– Rx symptoms & complicationsRx symptoms & complications

Fight inf.Fight inf. Cut down absorption of wastes/toxinsCut down absorption of wastes/toxins FEB. Salt restriction FEB. Salt restriction HemostasisHemostasis

Liver transplant SOSLiver transplant SOS Vax. against flu, pneumonia, hepatitisVax. against flu, pneumonia, hepatitis No hepatotoxic drugsNo hepatotoxic drugs No alcoholNo alcohol Diet: extra calories & a generous protein to help Diet: extra calories & a generous protein to help

liver regenerateliver regenerate If cirrhosis is advanced limit proteinIf cirrhosis is advanced limit protein

PORTAL PORTAL

HYPERTENSION IN HYPERTENSION IN

CHILDRENCHILDREN

IntroductionIntroduction Portal vein: Portal vein: SV with SMV: carries 70% of liver blood. SV with SMV: carries 70% of liver blood.

Ends in sinusoidsEnds in sinusoids Double capillariesDouble capillaries PH: PH: raised pressure in PV >raised pressure in PV >11mmHg 11mmHg or a splenic pulp or a splenic pulp

pressure of >16mmHg. Clinically this is not measured pressure of >16mmHg. Clinically this is not measured directly until a TIPS is decideddirectly until a TIPS is decided

SV: splenic vein. SMV: superior mesenteric vein. PH: portal hypertensionSV: splenic vein. SMV: superior mesenteric vein. PH: portal hypertensionTIPS: transjugular intrahepatic portosystemic shuntTIPS: transjugular intrahepatic portosystemic shunt

PH: PH: splenomegaly splenomegaly & & porto-systemic shunts at:porto-systemic shunts at:

Lower end of Lower end of eophagus eophagus via GE veins: via GE veins: hemat./malenahemat./malena Anal Anal veins: veins: hemorrhoidshemorrhoids Umbilical Umbilical veins: veins: caput medusacaput medusa Abdominal wall & retroperitoneum: Abdominal wall & retroperitoneum: distended veinsdistended veins

GE: gastroesophagealGE: gastroesophageal

Eesophageal varicesEesophageal varices• Gastroesophageal junction to 15cm upGastroesophageal junction to 15cm up

• Slow oozing or sudden severe hgeSlow oozing or sudden severe hge

Gastric varicesGastric varices

Extension of esophageal varices or varices in Extension of esophageal varices or varices in fundus & upper body. Can occur alonefundus & upper body. Can occur alone

Rectal varices:Rectal varices: hemorrhoidshemorrhoids

Gastric varicesGastric varices

Rectal varicesRectal varices

Aetiology of Portal HTNAetiology of Portal HTN• IntrahepaticIntrahepatic:: 80% 80%

• CirrhosisCirrhosis is the commonest; scar tissue blocks BF & is the commonest; scar tissue blocks BF & slows liver functionsslows liver functions

•Schistosomiasis, cong. hepatic fibrosis, etc.Schistosomiasis, cong. hepatic fibrosis, etc.

• PrehepaticPrehepatic:: 20%20%•PV thrombosis:PV thrombosis:

• extension of obliterative process of umb. veinextension of obliterative process of umb. vein• omphalitis (in newborn)omphalitis (in newborn)

• PosthepaticPosthepatic (rare): cons. pericarditis, tricuspid (rare): cons. pericarditis, tricuspid incompetence, incompetence, Budd-Chiari syn. Budd-Chiari syn. (occlusion of HV)(occlusion of HV)

Cong. hepatic fibrosis: Cong. hepatic fibrosis: hematemesis, normal LFTs, hematemesis, normal LFTs, hepatomegaly. May have polycystic disease& other hepatomegaly. May have polycystic disease& other renal D. Etiology is unknownrenal D. Etiology is unknown

Hepato-portal sclerosis: Hepato-portal sclerosis: thickening of intrahepatic PV thickening of intrahepatic PV obstructs BF: leads to collateral veins in porta obstructs BF: leads to collateral veins in porta

hepatishepatis

Suprahepatic obstruction Suprahepatic obstruction c/by a web in the IVC or c/by a web in the IVC or Budd-Chiari syn. Extremely rare. CF may mimic Budd-Chiari syn. Extremely rare. CF may mimic constrictive pericarditis. DD by echo-, venographyconstrictive pericarditis. DD by echo-, venography

CF of portal hypertensionCF of portal hypertensionmay not always be specificmay not always be specific Splenomegaly (hypersplenism: pancytopenia)Splenomegaly (hypersplenism: pancytopenia) Caput medusaCaput medusa Hematemesis, melena or PR bleedHematemesis, melena or PR bleed AscitesAscites Encephalopathy: poor liver function & diversion of blood Encephalopathy: poor liver function & diversion of blood

away from liveraway from liver

DD of uncommon CLDDD of uncommon CLD

ConditionsConditions PresentationPresentationBudd-Chiari SynBudd-Chiari Syn AscitesAscites

Primary sclerosing Primary sclerosing Cholangitis (PSC)Cholangitis (PSC)

Abnormal LFT/jaundice Abnormal LFT/jaundice

Primary bil. cirrhosis (PBC)Primary bil. cirrhosis (PBC) Abnormal LFT, malaise, Abnormal LFT, malaise, lethargy, itchinglethargy, itching

Caroli diseaseCaroli disease Abdominal pain/sepsisAbdominal pain/sepsis

Simple liver cystSimple liver cyst Pain/coincidental findingsPain/coincidental findings

Polycystic liver diseasePolycystic liver disease Pain/hepatomegalyPain/hepatomegaly

Diagnosis: Diagnosis: by detecting CLD, encephalopathy, ascites, by detecting CLD, encephalopathy, ascites,

varices.varices. Investigations: Investigations: esophagoscopy, Ba-swallow, esophagoscopy, Ba-swallow, USG, celiac axis angiogramUSG, celiac axis angiogram

PV Thrombosis: PV Thrombosis: Dx is difficultDx is difficult

may present within 5y age as hematemesis with only may present within 5y age as hematemesis with only splenomegaly & low plateletsplenomegaly & low platelet

• H/of umbilical V cannulation & abdo. sepsis (40%), or H/of umbilical V cannulation & abdo. sepsis (40%), or trauma/pancreatitis. PVT is mainly congenital. LFTs in trauma/pancreatitis. PVT is mainly congenital. LFTs in these these are normal. USG may confirm PVT: collateral veins are normal. USG may confirm PVT: collateral veins in the in the porta hepatis replacing the PVporta hepatis replacing the PV

TreatmentTreatmentEsophageal variceal bleeding:Esophageal variceal bleeding:

By the time pt. reaches ERBy the time pt. reaches ER

- 1/31/3rdrd – stopped bleeding – stopped bleeding

- 1/31/3rdrd – still oozing – still oozing

- 1/31/3rdrd – still bleeding heavily – still bleeding heavily

Initial measures: ICUInitial measures: ICU- BT: up to 10 unitsBT: up to 10 units- LFT: coagulation profileLFT: coagulation profile- If <50,000, platelet transfusion- If <50,000, platelet transfusion- Endoscopic evaluation & treatment- Endoscopic evaluation & treatment

• Encephalopathy: may need ventilatorEncephalopathy: may need ventilator

• Bronchial aspiration – a frequent complicationBronchial aspiration – a frequent complication

• If profuse bleed prohibits endoscopy:If profuse bleed prohibits endoscopy:• Insert Sengstaken – Blakemore tube & tamponade; Insert Sengstaken – Blakemore tube & tamponade;

deflate after 12h to avoid pressure necrosisdeflate after 12h to avoid pressure necrosis

Endoscopic sclerotherapyEndoscopic sclerotherapy

- Ethanolamine oleate- Ethanolamine oleate

- Sodium tetradesyl sulphate- Sodium tetradesyl sulphate

- 5% phenol in Almond oil- 5% phenol in Almond oil

- Butyl cyanoacrylate- Butyl cyanoacrylate

DrugsDrugs

• I/V Vasopressin. SE: Abdo. crampsI/V Vasopressin. SE: Abdo. cramps• I/V Octreotide (Somatostatin analogue): Equally I/V Octreotide (Somatostatin analogue): Equally

effective, safeeffective, safe

TIPSSTIPSS (transjugular intrahepatic portosystemic stent) (transjugular intrahepatic portosystemic stent) revolutionized the Rxrevolutionized the Rx

• Main Rx for drug resistant cases or in endoscopic Main Rx for drug resistant cases or in endoscopic therapy failuretherapy failure

Surgical shuntSurgical shunt

(Replaced by TIPSS & liver transplant)(Replaced by TIPSS & liver transplant)

Surgical shunts:Surgical shunts:

• splenorenalsplenorenal

• portocaval portocaval

SE: encephalopathy (40%)SE: encephalopathy (40%)

No benefit for pts. who have no bleedingNo benefit for pts. who have no bleeding

C.I. C.I. of Liver transplantof Liver transplant

• Age >65 yAge >65 y

• H/o IHD, HF, Chr. Respiratory diseaseH/o IHD, HF, Chr. Respiratory disease

• Previous Surgical shunts (relative C.I.)Previous Surgical shunts (relative C.I.)

Rx of Ascites of CLDRx of Ascites of CLD

• Salt restrictionSalt restriction

• DiureticsDiuretics

• ParacentesisParacentesis

• Peritoneovenous shuntingPeritoneovenous shunting

• TIPSSTIPSS

• Liver transplantLiver transplant

MCQMCQ

Hepatitis A & E are common c/of CLDHepatitis A & E are common c/of CLD Vaccines for HBV protects against HDVVaccines for HBV protects against HDV Haemorrhoids in cirrhosis are due to HC failureHaemorrhoids in cirrhosis are due to HC failure Palmer erythema is normal in pregnancyPalmer erythema is normal in pregnancy Commonest c/of PHT is cirrhosisCommonest c/of PHT is cirrhosis

MCQMCQ Commonest surgical c/of cirrhosis in children is Commonest surgical c/of cirrhosis in children is

biliary atresiabiliary atresia Edema in CLD starts in legsEdema in CLD starts in legs CLD may be idiopathicCLD may be idiopathic Autoimmune LD have good prognosisAutoimmune LD have good prognosis A1AT protects lungsA1AT protects lungs

THANK YOU