Transcript Objectives, Primary indications of liver transplantation in Europe

This lecture was conducted during the Nephrology Unit
Grand Ground by Medical Student rotated under Nephrology
Division under the supervision and administration of Prof.
Jamal Al Wakeel, Head of Nephrology Unit, Department of
Medicine and Dr. Abdulkareem Al Suwaida, Chairman of
Department of Medicine. Nephrology Division is not
responsible for the content of the presentation for it is
intended for learning and /or education purpose only.
Presented by:
Rinda Mousa
Medical Student
December 17, 2008
Objectives
• 1- Cirrhosis
• 2-Major sequelae of cirrhosis
Portal hypertension
variceal haemorrhges
Ascites
H encehalopathy
Hepatorenal sy.
Heamatologic changes
• 3- GET an idea on the management
of these complications
What is Liver
cirrhosis
What is Liver cirrhosis
• Diffuse, irreversible fibrosis
plus hepatocellular nodular regeneration
Causes of cirrhosis
• 1- Alcohol “85%” Europe
• 2- Ch viral hepatitis <com. Cause KSA esp: HBC>
• 3- genetic
Hemochromatosis , wilson dis
• 4- biliary cirrhosis
primary
secondary
• 5- Autoimmune diseases(autoimmune hepatitis)
• 6- Drug & toxins(methotrexate , methyldopa)
• 7- ch hepatic congestion
Cardiac cirrhosis (CRHF, Constrictive pericarditis)
Hepatic vein thrombosis (Budd-Chiari)
Clinical features of cirrhosis
• Slow, insidious progression (years,
decades)
• Presentation varies from asymptomatic
abnormal liver function tests to end-stage
liver disease
• Pts seek medical help only after the onset
of
alarming
complications
symptoms
and
severe
Major sequelae of cirrhosis
• Portal hypertension
variceal bleeding;
splenomegaly,
hypersplenism
• Ascites
• H encehalopathy
• Hepatorenal sy.
• Synthetic dysfunction
coagulopathy;
albumin!
• Altered drug
metabolism
• Feminization
• Hepatic
osteodystrophy
• Cholelithiasis
• HCC
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Xanthelasma
Scleral icterus
Jaundice
Fetor hepaticus
Parotid hypertrophy
Spider angioma
Gynecomastia
Ms wasting
Bleeding
tendency(bruising)
Anemia
Palmar erythema
Dupuytern’s cont
astrexis
Ankle edema
Visible signs
of advanced liver
cirrhosis
Gynecomastia
Ascites
Caput Medusae
Umbilical hernia
jaundice
Jaundice and Scleral Icterus
KF Ring of Periphery of Iris
Parotid Hypertrophy contributes to the rounded
appearance of the face; the submandibular glands
may also be enlarged.
Spider Naevi are found only in the distribution of the
superior vena cava, most commonly on the face and the
anterior chest wall. They comprise an enlarged central
arteriole from which vessels radiate in a spoke-like
manner.
Palmar Erythema is charactarized by a prominent rim of
colour beginning on the hypothenar border of the hand but
also in some individuals involving the thenar eminence and
even the fingertips. Similar changes nay be observed on
the soles of the feet.
Dupuytren's Contractures arise as a result of fibrous
change in the palmar fascia which inserts into the flexor
tendons, most commonly affecting the ring fingers
Diagnosis of liver cirrhosis
• The gold standard: liver biopsy histology
• Without biopsy (contraindications!):
diffuse, chronic liver disease
(history, physical, laboratory and US
findings)
with evidences of portal hypertension
(oesophageal varices on gastroscopy;
dilated portal vein and its branches by US)
Normal Liver Histology
CV
PT
Cirrhosis
Fibrosis
Regenerating Nodule
MRI Cirrhosis
Mx of liver cirrhosis
• Treat underlying disorder
• Alcohol cessation
• Follow pat for complications/liver
transplant for end stage dis
• Prognostic factors include :
•Prognosis
Child-TurcottePugh Scoring
of Liver Disease
Severity
PT= 12 – 15 sec
Bilirubin = 2-17 mmol/L
{0.1-1 mg/dl}
Albumin= 36 -50 g/L
Child-Turcotte-Pugh Scoring
of Liver Disease Severity
Parameter
1 point 2 points
INR
<1.7
1.7 – 2.3
> 2.3
Bilirubin (uM)
<35
35-50
>50
Albumin (g/l)
>35
30-35
<30
Encephalopathy
none
mild (gr. 1-2)
severe (gr. 3-4)
Ascites
none
moderate
severe, refractory
Class A = 1-6; Class B = 7-9;
3 points
Class C = 10-15 points
Portal hypertension:
{ P. = R X B F }
increased resistance to portal vein blood flow
• Causes
– Pre-Sinusoidal
• portal vein thrombosis
– Sinusoidal
• Cirrhosis
• Alcoholic hepatitis
– Post-Sinusoidal
• Sever right heart failure
• Constrictive pericarditis
• Hepatic vein out flow
obstruction
ANATOMY OF THE PORTAL
VENOUS SYSTEM
Portal HTN
Portal HTN
Splenomegaly
Esophageal Varices
Caput Medusa
Cirrhosis
MX
• 1- B-blockers “propanolol” and
nitrate
• 2-shunt
Varices
• Esophagus
• Gastric
• Colorectal
Oesophageal varices
Oesophageal varices
Bleeding Gastric Varices
Varices “Dx”
•
•
•
•
Hx : hematemases , melena
Physical examination
US abdomen
Endoscopy
Varices
Mx -GENERAL
•
•
•
•
•
•
ABC
2 IV lines
Type & cross match
Resuscitation ( IVF , BL )
Platelet transfusion ( platelet < 75.000 )
Fresh frozen plasma ( correct pt)
Varices
Mx - specific
• IV vasoconstrictors ( Octrerotide )
• Endoscopic therapy
- banding
- sclerotherapy
• Shunt surgery ( only if no cirrhosis)
Variceal banding
Variceal Bander
Variceal Band Ligation
Sengstaken-Blakemore Tube
Varices
Prevention
• Treat underlying dis
• Endoscopic banding protocol
• B-blockers
• Shunt surgery ( only if no cirrhosis)
• Liver transplantation
Ascites
• Def:
Pathological Fluid in the peritonial cavity
OSCE
station
The Development of Ascites
• N physiology :
Intravascular HP & OP are balanced (starling forces)
prevent accumulation of fluid in to peritoneal space
• In cirrhosis :
HP & OP balance is disrupted
Precipitating ascites by one or more of the following mech:
1-fibrotic constriction of sinusoid resulting in P HTN and
increased HPincreased HP drives fluid lymphatic
drainage into the abd via hepatic capsule
2-hypoalbuminemia  decrease OP
3- renal hypoperfusion  Na and
H2O retention “RAA syt
Cirrhosis
Renal hypoperfusion
Activation of renin-angiotensin-aldosterone system
Na retention
&
Water retention
Ascites
Causes of
ascites
Classification of Ascites by
Serum Albumin-Ascites Gradient
• High
albumin gradient
(SAAG > 1.1 g/dl)
• Decrease
albumin gradient
(SAAG < 1.1 g/dl)
*Cirrhosis
*Alc hepatitis
*CHF
*Massive hepatic
metastases
*
•
•
•
•
PHTN or HF
Peritoneal dis or kidney
dis
Peritoneal ca
“ TB
Pancreatitis
Serositis
NS
Presentation
• History :
• Increased abdominal girth
• Increased wt
• Physical exam :
• Bulging flanks
• Shifting dullness
• Fluid wave
Diagnosis
• Physical examination
• US
• Ascitic tap
1* cell & dif
2* chemistry
3*C + S ,gram stain
4*cytology
Treatment - General
• Treat the underlying disease
• Salt restriction (< 2 mg /d )
• Diuretics
-Loop diuretic ( Lasix )
-Aldactone inhibitor
( Spironolactone
)
The Development of Ascites
Cirrhosis
Renal hypoperfusion
Activation of renin-angiotensin-aldosterone system
Na retention
&
Water retention
Ascites
Aldactone
inhibitor
( Spironolactone)
Treatment - Resistant
•
•
•
•
Recurrent tapping
Peritoneal-venous shunt
TIPS
Liver transplantation
Spontaneous bacterial peritonitis
(SBP)
• Infection of ascitic fluid
• Usually gram negative( E.Coli)
• Presentation variable
• Mortality is high
• Dx : ascitic tap =
WBC > 500
PMN > 250
+ve culture
G stain +ve (50%)
• Treatment: 3rd generation cephalosporin
IV
Hepatic encephalopathy
• Reversible decrease in neurological
function secondary to liver disease
• Acute : seen with acute liver failure
• Acute on chronic : established cirrhosis
Pathogenesis of Hepatic
Encephalopathy
BRAIN
Porta systemic
shunts
LIVER
Toxic N2 metabolites
From Intestines
Ammonia
Fatty acids
Amino acids
Clinical stages of Hepatic
encephalopathy
• I : Apathy , restlessness ,
,reversal of sleep rhythm , impaired handwriting
• II : Asterixis , drowsiness , disorientation
• III: Stupor,
Hyperactive reflexes , Extensor plantar
responses
• IV : coma (response to painful stimuli only)
Hepatic encephalopathy
Exacerbating factors
•
•
•
emorrhage /
ypokalemia
xcess dietary prot
aracentesis
•
cidosis / nemia
•
rauma
•
nfection
•
olon surgery / onstipation
•
edatives
Hepatic encephalopathy
Diagnosis
• Clinical ( most imp )
Only pathognomonic finding is fetor hepaticus
• The drawing tests
• EEG (bilateral synchronous showering of the
wave frequency with increase in wave
amplitude)
• CT / MRI may show cerebral atrophy
Drawing tests
Flapping tremor
PATHOPHYSIOLOGY
??
Hepatic encephalopathy
Treatment
•
Identify and treat precipitation factor & underlying
liver disease
•
Decrease generation of nitrogenous compounds
# Decrease dietary prot to 50g/d ” No
evidence for low protein diet”
#
- lowering PH (H* + NH3  NH4 ”nondiffusable”)
- Laxative to eliminate nitrogen-producing bact
from colon
•
Antibiotics ( Neomycin , Metronidazole )
•
Transplantation
Hepatorenal syndrome
•
•
•
•
•
•
•
•
Severe renal vasoconstriction
Progressive renal failure
Type 1 : rapidly progressive , high mortality
Type 2 : slower progression
No effective treatment
R/O volume depletion 2ry to diuretics
IV vasoconstrictors
Liver transplantation
6*
Hematologic changes
in Cirrhosis
Pancytopenia from hypersplenism
Decrease clotting factors
“ Fibrin, thrombin I ,II ,V, VII ,IX ,X “
Summary
• 1- Mechanical compression of blood flow
plus hemodynamic changes leads to portal
HTN
• 2- Common complications of portal HTN
are:
-Collateral formation (varices )
-Ascitis
-Hepatic encephalopathy
• 3- The most imp step in variceal bleed
management is resuscitation
• 4- The most important step in
management of hepatic encephalopathy is
the identification of the precipitating factor
Ask about causes :
• Hepatitis: blood transfusion , contact with
jaundiced or hepatitis pt, sexual contact, IV drug
abuse ,IV injections , tattos.
• Alcohol consumption
• Drug intake (hepatotoxic drugs)
• Heamochromatosis: receiving freq Bl Tx, iron
therapy or skin pigmentation
• 1ry biliary cirrhosis: jund , itching , pale stool &
dark urine <R/O Obstructive gallstone
• Familial: similar problem in the family
Complications
• Ascitis : (abd dist)
• Decrease Liver function: (LL edema d.t
hypoproteinemia,epistaxis or easily bruising d.t
decrease production of CF , impotance in males,
amenorrhea in females)
• Hepatic encephalopathy : (confusion
,drowsiness , coma , altered sleep pattern)
• Esophygial varices : ( hematemesis , melena
,any endoscopic procedure)
• Hyperspleenism : ( dragging pain in LT
hypochondria)
Learn from the
mistakes of others.
You can't live long
enough to make them
all yourself…!