au,cirrhosis

AU, SHH ASELLADEP’T OF INTER.MEDICINE

LECTURE ON CIRRHOSIS FOR YR-III MEDICAL STUDENTS DR NUWAMA BIFA

Topic --- CIRRHOSIS

OBJECTIVE : Should be able to define cirrhosis Should be able to classify cirrhosis Should be able to work up CLD be able to mention complications of

CLD

CONTENT ----------------- TIME

Introduction -------------------- 1’ Definition ------------------------0.5’ Etiologic classification----------25’ Pathogenesis ---------------------3’ Clinical presentation ------------10’ Diagnosis --------------------------10’ Staging ----------------------------- 3’ Management outline--------------3’

liver -- receives a dual blood supply; ~20% of the blood flow is oxygen-rich blood from the hepatic artery, and 80% is nutrient-rich blood from the portal vein arising from the stomach, intestines,pancreas,andspleen

(almost from entire GI- through Superior /

Inferior mesentry)

LIVER CELLS hepatocytes, constitute 2/3 stellat (13% ) Kupffer cells endothelial cells and blood vessels, bile

ductular cells, and supporting structures

Liver cells : 1-- hepatocytes, constitute 2/3.has distinct

polarity; Disse space & microvilli with passive and active uptake of nutrients, proteins, and other molecules.

Plays vital roles in maintaining homeostasis and health; synthesis serum proteins (albumin, carrier proteins, coagulation factors, many hormonal and growth factors), the production of bile and its carriers (bile acids, cholesterol, lecithin, phospholipids), the regulation of nutrients (glucose, glycogen, lipids, cholesterol, amino acids), and metabolism and conjugation of lipophilic compounds (bilirubin, anions, cations, drugs) for excretion in the bile or urine.

2-- Kupffer cells (reticuloendothelial system), lie within the sinusoidal vascular space and represent the largest group of fixed macrophages in the body.

3---stellate (Ito,fat-storing ) 13%- (retinoid;vitA metabolite storage), not prominent unless activated, when they produce collagen and matrix in large.

4-- endothelial cells and blood vessels, bile ductular cells, and supporting structures.

NORMAL LIVER HISTOL

DEF :

Def : cirrhosis is irreversible hepatic damage ; histologically characterized by loss of hepatic architecture with fibrosis & nodular regeneration.

ETIOLOGY OFCIRRHOSIS

ALCOHOLHEPATOTROPHIC VIRAL HEPATITIS: - HCV -HBV -HV-Coinfection(HBV+HCV, HBV+HDV) -HV-Coinfection with HIV -HV-Alcohol abuseAUTOIMMUNE HEPATITIS (AIH)BILLIARY DISEASES:

PRIMARY(Psc/PBC) SECONDARY: obstructive;cholangitis

ETIOLOGY OF CIRRHOSIS……

HERIDETARY METABOLIC DISEASES -HEMOCHROMATOSIS -WILSON’S DISEASE -ALPHA1-ANTITRYPSIN DEFICIENCY(AAT ) -CYSTIC FIBROSIS -GLYCOGEN DISEASE VASCULAR DISEASES: -VENO-OCCLUSIVE DISEASE(VOD) -BUDD-CHIARI SYNDROME(BCS) -CHF/ Percarditis( CARDIAC CIRRHOSIS)

Drugs: Metotrixate, amiodarone,

Toxins: Carbon tetrachloride, diethylmitrosamide

Idiopathic Indian childhood cirrhosis Cryptogenic

ALCOHOLIC LIVER DISEASES :

Alcoholic cirrhosis :

Chronic & excessive ingestion

Risk factors:

A, quantity-M-60-80g/d for 10-20yrs F -20-40g alcohol/d for shorter NB-1beer =12g alcohol(ethanol)B, duration –chronic consumptionC, genderD, concurrent hepatitisE,genetic –genepolymorphism; ADHF, malnutrition –obesity – fatty liver

ADH ALDHAlcohol ---------- acetaldehyde --Acetate highly reactive with protein(by reactive O2) & form adduct Stellate cells ACTIVATION COLLAGEN PRODUCTION

CIRRHOSIS – CHRONIC VH

HCVPredictive factors for diseases progression

:

A-host factor ; age 40+ at acquisition,Cimminity –

rapid pB-viral factors : d/t genotype,viral loadC- alcohol intakeD- HIV –coinfection HCC

NATURAL HX OF HCV

HBV Progression vary with :

1-function of age(viralrepli/immunit-interplay)

NB –perinatal infection 90%cirrhosis - adult infection < 5%

2 –alcohol consumption3 –concomitant HDV ,HIV infection

HBsAg Anti-HBs IgM anti-HBc IgG anti-HBc HBeAg Anti-HBe viral copies/mL Interpretation

+ − + − + − + Acute infection; occasionally “reactivation” of chronic hepatitis B − + − + − −/+ − Prior infection with immunity − + − − − − − Vaccination with immunity + − − + − + <105 Chronic hepatitis B without replication + − − + + − >105 Chronic hepatitis B with replication + − − + − + >105 Chronic hepatitis B with precore mutant Anti-HBc, hepatitis B core antibody; anti-HBe, hepatitis B e

antibody; anti-HBs, hepatitis B surface antibody; HBeAg, hepatitis B e antig

NONALCOHOLIC STEATOHEPATITIS(NASH)

Risk : obesity, hyperlipidemia,DM,

Histology: fatty change & inflammation

CHRONIC CHOLESTATIC LIVER DISEASES(PRIMARY&SECONDARY)

Primary biliary cirrhosis(PBS) : progressive granulomatous inflamm

interlobular bile ducts damage cirrhosis

Cause : unknown ? Autoimmune ,Affect : 90% middle age women

Primary sclerosing cholangitis(PSC)

Progressive obliterative inflamm of intra & extra hepatic bile ducts fibrosis cirrhosis

Cause : unknown ? Autoimmune >70% asssociate with Ulcerative

colitis

METABOLIC

Hemochromatosis:

Autosom disorder of Fe metabol X-ed by high Fe absorption deposition in multiple organs (LIVER, PANCREASE, HEART ,PITIUTARY, JOINT)

Affect : middle age men, loss through

mensus protect women.

Wilson’s Disease : Inherited disorder X-ed by failure to

excrete copper(failure to prepare Cu,transportingATPase , for biliary excretion) accummulation of toxicCu in LIVER&BRAIN

Kayser-Fleischer ring : pathognomonic(usually) brownish pigment ring at the periphery of cornea

Alpha 1-antitrypsin deficiency

Inherited disorder causes abnormal folding of AAT protien failure of Liver secretion accumulation in hepatocytes Liver damage

NEONATE :cholestasisearlychildhood cirrhosisADULT :- cirrhosis HCC

NB:-lung is affected due to destrucion

ELASTASE AAT - Elastin (protien) destruction of protien

PATHOGENESIS OF CIRRHOSIS

LIVER INJURY( CHRONIC) OF ANY CAUSE ACTIVATION STELLATE,Endothelial,Kupffer,..Cells Collagen production Fibrogenesis(wound healing)

PATHOGENESIS…Hepatocytes microvilli & Endothelial

fenestration lost Micro/Macronodular Regeneration Metabolic &synthetic dysfunction of

hepatocytes DECOMPANSETED LIVER END STAGE

NORMAL-LIVER HISTOL

ACTIVE SEPTUM( FIBROSIS) ,CIRRHOSIS

PASSIVE SEPTUM( FIBROSIS)

MICRONODULAR ,CIRRHOSIS

MACRONODULAR ,CIRRHOSIS

CLINICAL MANIFESTATION

1/3 asymptomatic

History: Hx of alcohol, drug abuse, blood Tx,

familly ds, Weakness, fatigue, wt loss, anorexia,

flatulent dyspepsia,abdominal pain, impotence/↓libido, jaundice, leg/abdom swelling, GI/skin hemorrhage

may present with life-threatening complications:

~variceal hemorrhage, ~ascites, ~spontaneous bacterial peritonitis (SBP) ~hepatic encephalopathy.

CM… Physical signs: Fever Atrophic legs and arms Parotid enlargement Testicular atrophy Ascites & edema, hydrothorax/effusion Portal HTN/splenomegally Asterixis, confusion,fetor hepaticus

DERMATOLOGICAL SIGNS OF CIRRHOSIS:

Spider angiomas/nevi,(found in 50% pregnant) Telangectasias Palmar erythema Pigmentation Purpura, white nails Finger clubbing, Dupytrens contructure

Abdominal collaterals Axillary & pubic hair

loss Kayser-Fleischer ring(

cornea) Asterixic(flapping) Testicular atrophy

Spider angiomata/ spider telangiectasias-- are vascular lesions consisting of a central arteriole surrounded by many smaller vessels on trunk, face, and upper limbs.

pathogenesis is incompletely understood, believed to result from alterations in sex hormone metabolism; in men increase in the estradiol/free testosterone ratio

not specific for cirrhosis can be seen during pregnancy ,

severe malnutrition.

As a general rule, the number and size of spider angiomata correlate with the severity of liver disease . Patients with numerous and large spider angiomata may be at increased risk for variceal hemorrhage.

Palmar erythema — exaggeration of the normal speckled mottling of the palm, believed to be caused by altered sex hormone metabolism . on the thenar and hypothenar eminences while sparing the central portions of the palm. not specific for liver disease ,can be seen in pregnancy rheumatoid arthritis, hyperthyroidism, and hematological malignancies.

Muehrcke's nails --paired horizontal white bands separated by normal color. caused by hypoalbuminemia .not specific for cirrhosis, also be seen in other conditions with hypoalbuminemia.

Clubbing — angle b/n nail plate and proximal nail fold >180degree. severe form[grade4] is drum stick. more common in biliary causes of cirrhosis (particularly primary biliary cirrhosis) ,but not specific for liver disease.

Dupuytren's contracture — thickening and shortening of the palmar fascia with flexion deformity ,fibroblastic proliferation and disorderly collagen deposition with fascial thickening. The pathogenesis is unknown but may be related to free radical formation generated by the oxidative metabolism of hypoxanthine

Gynecomastia — benign proliferation of the glandular tissue of the male breast and clinically by the presence of a rubbery or firm mass extending concentrically from the nipple(s). Fat deposition without glandular proliferation is termed pseudogynecomastia ( obese men). These two entities can be distinguished by having the patient lie on his back with his hands behind his head. The examiner then places his or her thumb and forefinger on each side of the breast, and slowly brings them together.

caused by increased production of androstenedione from the adrenals, enhanced aromatization of androstenedione to estrone, and increased conversion of estrone to estradiol. Men may also develop other features reflecting feminization such as loss of chest or axillary hair and inversion of the normal male pubic hair pattern. Gynecomastia can be seen in a variety of conditions other than cirrhosis.

Testicular atrophy — Hypogonadism is manifested by impotence, infertility, loss of sexual drive, and testicular atrophy. It is a feature seen predominantly in patients with alcoholic cirrhosis and hemochromatosis. More than one mechanism appears to be involved. In some cases, primary gonadal injury appears to be more prominent, as suggested by increased serum FSH and LH concentrations, while in others suppression of hypothalamic or pituitary function appears to have a primary role, as suggested by serum LH concentrations that are not elevated. The toxic effects of alcohol or iron may also contribute to its development.

Hepatomegaly — cirrhotic liver may be enlarged, normal sized, or small. While the presence of a palpable liver may indicate liver disease, a non-palpable liver does not exclude it. When palpable, the cirrhotic liver has a firm and nodular consistency.

Splenomegaly — caused by congestion as the result of portal HTN .

other several ddx are possible.. Ascites — accumulation of fluid in the peritoneal cavity. The

accuracy of physical findings is variable depending in part upon the amount of fluid present, the technique used to examine the patient, and the clinical setting (eg, detection may be more difficult in patients who are obese). In one study, the absence of flank dullness was the most accurate predictor against the presence of ascites; the probability of ascites being present was less than 10 percent in such patients . However, approximately 1500 mL of fluid had to be present for flank dullness to be detected. Shifting dullness is more specific.

Caput medusae — The veins of the lower abdominal wall normally drain inferiorly into the iliofemoral system while the veins of the upper abdominal wall drain superiorly into the veins of the thoracic wall and axilla. When portal hypertension occurs as the result of cirrhosis, the umbilical vein, normally obliterated in early life, may open. Blood from the portal venous system may be shunted through the periumbilical veins into the umbilical vein and ultimately to the abdominal wall veins, causing them to become prominent. This appearance has been said to resemble the head (caput) of the mythical Gorgon Medusa.

Dilated abdominal veins can also be seen in the IVCS and SVCS (if obstruction includes the azygous system) . In these conditions, collateral veins tend to be more prominent in the lateral aspect of the abdominal wall. One maneuver that has been proposed to distinguish vena caval obstruction from portal hypertension is to pass the finger along dilated veins located below the umbilicus to strip them of blood and determine the direction of blood flow during refilling. In portal-systemic collateral veins, the blood flow should be directed inferiorly away from the umbilicus in contrast to vena caval collateral vein flow in which the flow should be cephalad. However, the actual ability of this maneuver to discriminate between the two is poor since in both conditions the dilated veins may lack valves and thus have bidirectional blood flow .

Fetor hepaticus — A sweet, pungent smell to the breath of a cirrhotic patient may occasionally be encountered. It is caused by increased concentrations of dimethylsulphide, the presence of which suggests underlying severe portal-systemic shunting .

Jaundice — yellow coloring of the skin and mucus membranes that results from increased serum bilirubin. It is usually not detectable until Tbil > 3 mg/dL. The hyperbilirubinemia may also cause the urine to appear dark or "coca-cola" colored.

Yellow discoloration to the skin can also be caused by excessive consumption of carotene ( carrots). But can be distinguished from jaundice by the absence of yellow discoloration in the sclera in the former.

Asterixis — bilateral but asynchronous flapping motions of outstretched, dorsiflexed hands ,is seen in patients with hepatic encephalopathy, ?may also be seen in patients with uremia and severe heart failure.

DIAGNOSIS

In most instances can be made accurately by a careful history, physical examination, and application of a few laboratory tests.

In some circumstances, radiologic examinations are helpful or, indeed, diagnostic.

Liver biopsy is considered the "gold standard"

in evaluation of liver disease but is now needed less for diagnosis than for grading and staging disease.

Lab LFT can be normal, >3-5x UNL or

1, AST(SGOT)

ALT(SGPT) <40Iu/ml AST/ALT <0.8 , >2 in alcoholic LD

2,Alk ph - usually elevated but <3X the upper normal limit. Higher levels in psc & pbc

3,Bilirubin (N T <1mg/dl;17microg/dl ,D<0.3

N in compensated, in advanced cirrhosis

4,Albumin- as the synthetic function of the liver declines with worsening cirrhosis;helps to grade the severity of cirrhosis.But not specific for liver disease,can be seen CHF, NS, protein losing enteropathy, or malnutrition.

5, Prothrombin time liver synthesize 11 blood coagulation proteins; Factor I

(fibrinogen), II (prothrombin), V , VII , IX , X , XII and XIII can be measured individually or indirectly by more

general measures of clotting ability such as the PT. CoagFactors ( liver capacity to synthesize) = PT

prolong

Globulins- in cirrhosis(infection), IgG in AIH ,IgM

in PBC

Serum Na+ — Hyponatremia is common in cirrhosis with ascites &severe in ESLD ; inability to excrete free water; high levels of ADHsecretion.

Hematologic abnormalities Anemia —  multifactorial ; acute and

chronic GI blood loss, folate deficiency, direct toxicity due to alcohol, hypersplenism,BMsuppression,ACD (inflammation), & hemolysis may all contribute.

Thrombocytopenia 

- portal HTN congestive splenomegaly sequestration of up to 90 % of circulating platelet mass.

- thrombopoietin

Leukopenia and neutropenia — due to hypersplenism

Imaging studies : U/S, Ctscan,MRI Angiography , ERCP/MRCP, UGIE,Echo

LIVER BIOPSY

Alcoholic liver disease- History of alcohol abuse , AST/ALT >2 Chronic hepatitis C- ELISA assay for anti-HCV ,PCR for HCV-

RNA PBC- Antimitochondrial antibodies PSC holangitis - Strong association with IBD, cholangi AIH -Hypergammaglobulinemia ,AntinuclearASMA,ALKA Chronic hepatitis B - HBsAg and HBeAg and, HBV DNA Hereditary hemochromatosis- Family history of

cirrhosis ,Serum ferritin & iron,transferritin satur>80% , TIBC ,biopsy-hepatic Fe index,genetic tes

Wilson's disease - Family or personal history of cirrhosis at a young age ,serum ceruloplasmim,biopsy -Co

AATdeficiency- Family or personal history of cirrhosis at a young age,serumAAT,phenotyping

NASH - History of diabetes mellitus or metabolic syndrome, hepatic imaging , biopsy

CHILD-PLUGH CLASSIFICATION OF SEVERITY

parameter score 1 2 3 1.ASCITES Abscent Slight Moderat2.BILIRUBIN <2mg/dl 2-3 >33.ALBUMIN >3.5g/dl 2.8-3.5 <2.84.PT <4sec 4-6 >6 INR <1.7 1.7-2.3 >2.35.HENCEPH None Grade1-2 G3-4

INTERPRETATION grade A- total score of 5-6 ;well-

compensated disease ;100-85% of 1-2yr survival

grade B- total score7-9 ;significant functional compromise ;80-60%of 1-2yr survival

grade C- total score 10-15 decompensated disease ;45-35% 0f 1-2yr survival.

MANAGEMENT OF CIRRHOSIS

goals :- Slowing or reversing the progression of

liver disease- Preventing superimposed insults to the

liver-Preventing and treating the

complications-Determining the appropriateness and

optimal timing for liver transplantation

ETIOLOGIC SPECIFIC THERAPIES Abstinence from alcohol . Interferon therapy to HCVslows the

progression,fibrosis &risk of HCC. Rx of chronic HB with

lamivudinsignificant improvement in liver function and histology & risk of HCC

Rx autoimmune hepatitis with immunosuppressive agents10yr survi 90 %

Phlebotomy , Chelation ,Dietary restriction of iron – for HH

Chelating –for wilson D

PREVENT INSULT

AVOID substance abuse; alcohol, acetaminophen ,NSAIDs hepatotoxic drugs & herbal remedies.

Give Vaccination — against HAV & HBV can prevent a superimposed insult to a liver

Pneumococcal vaccine yearly influenza vaccination

xumura

ULFAADHA !

SESSION -II

COMPLICATION OF END-STAGE CLD

OBJECTIVE

AT THE END :

Mention the complication. Rescribe the mechanism Work up principile Outline the managment

CONTENT ……. T COVERAGE

Portal hypertension -------------------------5’

Variceal hemorrhage -----------------------10’  

 Ascites -----------------------------------10’     Spontaneous bacterial peritonitis ------10’

Hepatic encephalopathy ------------------10’

COMPLICATION OF CIRRHOSIS Portal hypertension Variceal hemorrhage    Ascites      Spontaneous bacterial peritonitis    Hepatorenal syndrome    Hepatic encephalopathy    Hepatopulmonary syndrome Hepatocellular carcinoma Coagulopathy malnutrition

PORTAL HTN Def Causes Types consequence

PORTAL HTN

Def: hepatic venous pressure gradient (HVPG) > 5 mmHg. Portal pressure = Portal venous flow x portal venous

outflow resistance -R blood flow - vasodilatation within the splanchnic vascular

bed splanchnic blood flow.

Cause : cirrhosis-commonst >60% : noncirrhotic : ?idiopathic

TYPES :1 Prehepatic :Portal &/ or splenic vein thrombosis ,

:  Massive splenomegaly (Banti's syndrome)

2 Hepatic :commonst type 95%

2a PresinusoidalSchistosomiasis –fibrosis,Congenital hepaticfibrosis  

2b Sinusoidal Cirrhosis2c Postsinusoidalsinusoidal obstruction syndrome(VOD),BCS

3 Posthepatic : IVC obstruction ,

: Budd-Chiari syndrome   : Cardiac causes ;RCM Constrictive pericarditis

CLINICAL MANIFESTATIONS

1-- UGIB

2-- ascites

3—splenomegaly with hypersplenism.

VARICEA BLEEDING Def Location Risk Dx Rx

VARICEAL HEMORRHAGE

VARICES - are collateral vessels that develop because of PHT; 1/3of pts with cirrhosis & 1/3 of them will develop bleeding.

LOCATION— -distal esophagus (commonst) ; thinnest coat

and at risk to bleed, - stomach, -Rectum, -Umbilicus,…

FACTORS risk of bleeding : --PHTN >12mmhg ,-- severity of cirrhosis (Child's class),--size of the varix ,--location of the varix,-- endoscopic stigmata(red wale signs& …)

DX Endoscopy. Abdominal imaging, CT or MRI

demonstre nodular lesion Thrombocytopenia

RX OF VARICEAL BLEEDING

1-PRIMARY PROPHYLAXIS

a--Pharmacologic =nonselective beta blockade

(propranolol ,nadolol )

b--Endoscopic variceal band ligation(EVL) &/or

variceal injection therapy (sclerotherapy)

2- RX OF ACUTE BLEEDING (UGIB)a --- fluid and blood product replacement

b ---medical ; 1-somatostatin or Octreotide , Vasopressin= direct

splanchnic vasoconstrictor, is given at dosages of 50–100 g/h by continuous infusion.

c---surgical ;1-Balloon tamponade (Sengstaken-Blakemore tube or

Minnesota tube) 2- endoscopic therapy ( first-line to control active-vigorous

bleeding by EVL & /or variceal injection therapy (sclerotherapy)

3- transjugular intrahepatic portosystemic shunt (TIPS)under angiographic guidance

3 - PREVENTION OF RECURRENT BLEEDING

a---repeated variceal band ligation until varices are obliterated.

b---adjunctive Beta blockade (for recurrent variceal band ligation ,But no need once obliteration achieved)

c---TIPS

ASSIGNMENT

High risk group to develop reccurrent variceal bleeding ?

Prognosis of variceal bleeding ?

Other causes for UGIB ?

Risk factors for recurrent variceal hemorrhage Age >60 years Severity of initial bleed Renal failure Severity of liver failure Ascites Hepatoma Active alcoholism Active bleeding on endoscopy Increasing varix size Red signs yes coagulopathy Portal pressures

ASCITES Def Mechanism Dx Rx

ASCITES def: pathologic accumulation of fluid in the peritoneal

cavity

mechanism: multifactors1] PORTAL HYPERTENSION 

is the first step toward fluid retention in cirrhosis.>12 mmHg required.cirrhosis without PHT do not develop ascites ascites disappear if <12 mmHg

■Portal hypertension exerts a local hydrostatic pressure hepatic and splanchnic production of lymph &transudation of fluid into the peritoneal cavity.

2] Na RETENTION :

splanchnic vasodilatation-Arterial underfilling - Activation Renin-Ang-Aldos -- Na retent-

3] HYPOALBUMINEMIA :

synthetic function of cirrhotic liver Hypoalbuminemia plasma oncotic pressure loss of fluid from the vascular compartment into the peritoneal cavity.

CM-ASCITES incidious abdominal distension ;

( high Na diet,HCC ,splanchnic vein thrombosis Precipitate)

Abdominal pain ; SBP Respiratory distress ( Rt pleural effussion ) Malnourish; muscle wasting and excessive

fatigue and weakness. bulging flanks, fluid Waves ,shifting

dullness +v ,sign of pleural effussion.

DX-ASCITES abdominal imaging ; U/s , CT scan

Paracentesis : Analysis

Color (clear,straw,cloudy,bloody,milky,brown)

cirrhosis –straw/clear(if n-Bilir, protien)SBP –cloudyHCC –bloody

DXtest

1-Cell cout & diff - N >250 SBP

2-Gram stain,AFB and culture -

3-Protein -3.1 SAAG -3.2 [total protein]

4-Cytology - for malignant cells.

5-Amylase - to exclude pancreatic ascites

DX …test1-Cell cout & diff - N >250 SBP2-Gram stain,AFB and culture -

3-Protein- serum ascites-to-albumin gradient (SAAG) ; [total protein] in ascites is quite low in cirrhosis; <1 g/dL

SAAG=serum alb minus ascitic albumin ( not ratio ) High-gradient (transudative >1.1 g/dL indicates PHT-cirrhosis with

97%accuracy & remains stable unless PHT Low-gradient (exudative) <1.1 g/dl indicates abscence of PHT, but infectious(opsonization) or malignant (peritoneal carcinomatosis,

tuberculous peritonitis, pancreatitis, serositis, pyogenic peritonitis, and nephrotic syndrome)

4-Cytology - for malignant cells.5-Amylase - to exclude pancreatic ascites

DX… Bilirubin — in brown ascites. As

mentioned above, an ascitic bilirubin > of serum suggests bowel or biliary perforation into ascites

Glucose — Lactate dehydrogenase Triglycerides — milky/ Chylous ascites

has TG > 200 mg/dL

RX – OF ASCITES dietary sodium restriction spironolactone at 100–200 mg/d- 400–600mg

furosemide 40–80 mg/d- 120–160 mg/d

repeated large-volume paracentesis(refractory ascites)

TIPS (refractory ascites)

liver transplantation prognosis of cirrhosis with ascites is poor,

survive 2 years <50%

ASSIGNMENT LIST Other causes of ASCITES

SBP Def Etiology Precipitant Distinction from secondary BP Dx Rx

 SPONTANEOUS BACTERIAL PERITONITIS (SBP)

Def: ascitic fluid infection without an evident intraabdominal surgically-treatable source.

ETIOLOGIES ?

ETIOLOGY--------------RATE(%)

Escherichia coli 43% Klebsiella pneumoniae 11% Streptococcus pneumoniae 9%

Other streptococcal species 19% Enterobacteriaceae 4% Staphylococcus 3 % Pseudomonas 1% Miscellaneous* 10%

RISK FACTORS

cirrhosis,& associated conditions Ascitic [total protein] <1 g/dL (<10 g/L) Prior episode of SBP Serum [total bilirubin] > 2.5 mg/dL Variceal hemorrhage malnutrition Proton pump inhibitors Nephrotic ascites

MECHANISM

CM----------------------RATE(%)

Subtel- due to separation of visceral & parietal peritoneum

Fever 69 Abdominal pain 59 Altered mental status 54 Abdominal tenderness 49 Diarrhea 32 Paralytic ileus 30 Hypotension 21 Hypothermia 17

SECONDARY BACTERIAL PERITONITIS

Def : ascitic fluid infection in which there is a positive ascitic fluid bacterial culture and an ascitic fluid PMN count ≥ 250 cells/mm3 with an evident intraabdominal surgically-treatable source of infection .

Two varieties : 1--perforation peritonitis (eg, perforated peptic ulcer into

ascites) 2--nonperforation peritonitis (eg, perinephric absces

NB-mortality 100% if treatment consists only of antibiotics with no surgical intervention . And 80% if a patient with SBP receives an unnecessary exploratory laparotomy .

DISTINCTION SBP FROM 2*BPClinical  — both can be ( even frank perforation)

subtle b/c peritoneum separation by Ascites Analysis — PMN count ≥ 250 with two or more of [Total protein ] >1 g/dL (10 g/L)[ Glucose ]<50 mg/dL[ LDH >UNL for serum Imaging studies — plain and upright abdo minal films water-soluble gut contrast studies( extravasation

of contrast SBP-Rx response follow up --- with repeat analysis after 48hrs ; PMN is lower

DX Ascitic fluid analysis :

1] Cell count --- absolute PMNcount≥ 250 2] Culture ---- positive 3] SAAG ----- Low-gradient 4] [Total protien] -----lowest[ ] ; < 1g/dl5] [glucose] > 50mg/dl6] LDH (released from lysed PMNs) --[43 +/-

20mU/mL ] 7] [Amylase ]--- in pancreatitis and gut

perforation8] [ bilirubin] if dark/brown ascites----if > serum

value choleperitoneum ;GBperforation

RX

1- third-generation cephalosporin

? 2-combination of ampicillin and gentamicin .

Third-gener + metronidazolFor secondary BP

RX…

third-generation cephalosporin benefits over ampic/genta-combination:

A-- A higher rate of resolution of the infection — 85 versus 56 %

B--No /less nephrotoxicity versus 5 % with ampicillin-gentamicin

C-- No superinfection versus 14 percent with ampicillin-gentamicin

.

HE Def Mechanism Precipitant Stages Rx

HE

Def : ?potentially reversible neuropsychiatric syndrome seconday to liver diseases CLD,END-STAGE Or acute fulminant hepatic failure.

PATHOGENESIS:

Ammonia —  cause in >90% + other neurotoxins

Produced--- colonic bacterial catabolism of nitrogenous source; ingested protein and secreted urea.

Enters the circulation via the portal vein Liver clears almost all by converting into glutamine & prevent

entry into the systemic circulation In cirrhosis ,portal blood bypasses the liver via the collaterals

and the 'toxic'metabolites pass directly to the brain ( impaired liver blood ammonia ) Induced alteration of brain neurotransmitter balance -especially

at the astrocyte-neurone interface

PRECIPITANTS ?

HE …PRECIPITANTS High dietary protein

GI- haemorrhage

Constipation

Vomiting /Diarrhea

Infection; SBP , sepsis

Fluid and electrolyte ( k+ )disturbance due to:diuretic therapy,paracentesis

Drugs (e.g. anyCNSdepressant) Benzodiazepines,Narcotics ,Alcohol

Portosystemic shunt operations, TIPS Any

surgical procedure Progressive liver damage Development of hepatocellular carcinoma

HE..CM change in personality

confused

Can be quite violent and difficult to manage

Or very sleepy and difficult to arouse

Asterixis "liver flap”hepatic coma due Brain edema -herniation

HE…STAGE

RX … OF HE mainstay lactulose--, a nonabsorbable disaccharide

eliminat nitrogenous source

R x of precipitats

?Restriction of dietary protein

neomycin + metronidazole =Poorly absorbed antibiotics as adjunctive therapies or alternative to lactulose

rifaximin.

?Zinc supplementation

Prognostic worse as stage progress

THE HEPATORENAL SYNDROME

refers === development of acute renal failure in advanced liver disease, severe alcoholic hepatitis, (less often) metastatic tumor, and acute fulminant hepatic failure from any cause.

MECHANISM :

portal hypertension -splanchnic vasodilatation - hypotension-induced activation of the renin-angiotensin and sympathetic nervous system- renal perfusion ( GFR )

HRS…

Type I HRS--- more serious type; progressive impairment in renal function and a significant reduction in creatinine clearance ( 50% )within in <2wks,serum Cr.2.5mg/dl , oliguria

Type II HRS ; less severe. GFR and Cr

RX….HRS midodrine --is a systemic vasoconstrictor

alpha1–agonist--

octreotide -- inhibitor of endogenous vasodilator , in combination

intravenous albumin liver transplantation

prognosis is poor unless transplant can be achieved within a short period of time

HEATOCELLUAR CARCINOMA(HCC) 90% of primary hepatic malignancy One of the most common

malignancies ,4th leading death , affecr men commonly

1 million/yr with MR=250,000/yr Liver cirrhosis, HBV, HCV are most

important risk factors Most Asymtomatic or present with

abdomen pain or liver failure s/s Px=survive 2-6 months if unRxed

HCC… Causes of HCC: Viral infection: B,C,D; cirrhosis from HBV,HCV,

HH --at highest risk, while AIH,NASH &Wilson's d lower risk.HBV even at carrier state is high risk.

Toxins:Alcohol, aphlatoxin B1, tobaco,Thorium oxide, Vinyl chloride monomers

Metabolic liver ds:

hemochrom,alpha1,PCT,glycogen storageI, II

Others: BCS, Liver flukes, androgeic anabolic hormones, etc

HCC… S/S: nonspecific similar Hard irregular hepatomegally with bruit

and cachexia and splenomegally Portal vein thrombosis Coagulopathy Multiorgan failure Portal HTN

PATTERNS OF METASTATIC SPREAD —

 Extrahepatic -- most common sites are lung, intraabdominal lymph nodes, bone, and adrenal gland; brain metastases are extremely rare . Extrahepatic metastases are more common in patients with intrahepatic tumors >5 cm in diameter

HCC… DDX of primary hepatic malignancy: 1.Epithelial : HCC;cholangioca;bilary cystadenoca;Sq

cell ca; mucoepidermoid ca 2. Mesenchymal: Angiosercoma, hemangioendothelioma, Leimyosarcoma, fibrosercoma,

embryonal , sercoma, rhabdomyosercoma, Malignant schewanoma/ histosercoma,

lymphoma

HCC… 3. Mixed tumors: Hepatoblastoma Mixed HCC &cholangiocellular Ca carcinsarcoma

HCC… Treatment & prevention

Quarterly U/s & AFP for CLD for early HCC DX

RX: Ethanol, chemoembolz, resection, LTx, palliative care; RT, HormonalRx

Mass HBV vaccination and CLD Rx for prevention

CLINICAL FEATURES 

can be asymptomatic OR can present with complication of cirrhosis

RUQ pain ,weight loss , early satiety, or a palpable mass in the upper abdomen.

Obstructive jaundice r ,dyspnea ( metastases), Intraperitoneal bleeding ( tumor rupture)

Hepato/splenomegaly with bruit

Paraneoplastic syndromes — hypoglycemia, erythrocytosis, hypercalcemia, severe watery diarrhea,and cutaneous manifestation

Patterns of metastatic spread — Extrahepatic -- most common sites are

lung, intraabdominal lymph nodes, bone, and adrenal gland; brain metastases are extremely rare . Extrahepatic metastases are more common in patients with intrahepatic tumors >5 cm in diameter .

DX ….. HCC Alpha-fetoprotein --- glycoprotein that is

normally produced during gestation by the fetal liver and yolk sacr can pregnancy, with tumors of gonadal origin, and chronic liver disease ;acute or chronic viral hepatitis

NORMAL=10 and 20 mcg/L >500 mcg/L in high risk group is suggest

to HCCIMAGINGBIOPSY

RX …. HCC Surgical Liver transplant Radiotherapy/chemotherapy

MALNUTRITION IN CIRRHOSIS

regulation of protein and energy metabolism catabolic, and muscle protein is metabolized,

poor dietary intake, alterations in gut nutrient absorption, and alterations in protein metabolism.

Dietary supplementation is helpful

COAGULATION ANBORMALITIES Coagulopathy is almost universal in

cirrhosis. synthesis of clotting factors and

impaired clearance of anticoagulants. thrombocytopenia from hypersplenism Vitamin K absorption –

AFFECTdependent CF ( II, VII, IX, & X )

HEMATOLOGIC ABNORMALITIES

anemia from --persplenism, hemolysis, iron deficiency, and perhaps folate deficiency from malnutrition.

Macrocytosis Neutropenia from -hypersplenism.

BONE DISEASE Osteoporosis- malabsorption of vitamin

D & calcium ingestion

SOURCE HARRISON’S PRINCIPLES OF

INT.MEDICINE 17th EDITION UpTODate 17.2 KUMAR CLINICAL MEDICINE 6th EDITION