1. LIVER FAILURE DR MAGDI AWAD SASI 2015
Liver failure
FATTY LIVER OF PREGNANCY:
Occur near the end of pregnancy ,usually after the 35th
week.
Signs of preeclampsia are usually present((edema, hypertension
,proteinuria)).
The course is fulminant and florid jaundice
Coma occurs within 1st
week of symptoms
Immediate termination of pregnancy is essential for possible recovery of the
patient.
Pathologically,
Microvascular fatty infiltration of hepatocytes---centrilobular areas
Dilatation of smooth endoplasmic reticulum and mitochondrial changes
Microvascular fatty changes occurs in kidneys.
THE PROGNOSIS IN FHF:
Affected by:
A. The age of the patient ---high rate of death > 40 year
B. The etiology
The most determinant for out come
Increased death rate with drugs
Increased survival rate with HAV ,HBV
C. The clinical course
Admission before encephalopathy
Related to increased rate of survival 50%
D. The occurrence of secondary complication----bleeding ,hypoglycemia
E. The duration and severity of coma
THE POOR PROGNOSTIC SIGNS:
1. Increased PT to > 50
2. Decreased PH to < 7.3
3. Increased serum creatinine
CAUSES OF DEATH IN FHF:
1. Renal failure
2. Respiratory failure
3. Neurological complications—cerebral edema 80%
4. Gastrointestinal haemorrhage 13%
5. Bacterial infection and sepsis 13%
6. Hemodynamic complications
2. LIVER FAILURE DR MAGDI AWAD SASI 2015
CAUSES OF FHF :
1. Infections :
Viral agents ---HAV ,HCV ,HBV ,herpes ,yellow fever ,leptospirosis, Delta
2. TOXIC HEPATITIDES---DRUGS& TOXINS:
Paracetamol ,Halothane ,Isoniazide ,Hydrocarbons ,White phosphorus ,
Mushroom poisoning ( Amanita phalloides) ,amine oxidase inhibitor, CCL4
3. VASCULAR----ISCHEMIC LIVER NECROSIS:
Acute budd chiarri syndrome
Wilsons disease with intravascular hemolysis
Congestive heart failure
Shock ----hypoxia ,hypotension
4. ACUTE STEATOSIS SYNDROME:
Reyes syndrome
Acute fatty liver of pregnancy
Tetracycline induced fatty liver
DDI--- dideoxyinosine ---used in AIDS
Fatty liver after jejunoileal bypass surgery
5. AUTOIMMUNE:
Primary biliary cirrhosis ,autoimmune hepatitis, antitrypsin deficiency
6. Massive blastic infiltration of the liver:
A. Lymphoreticular malignancies:
i. Malignant histocytosis
ii. Hodgkins lymphoma
iii. Non hodgkins lymphoma
iv. Burkitt lymphoma
B. Acute leukemia:
i. Acute monoblastic leukemia
ii. Acute phase of chconic myelogenous leukemia
FHF SYMPTOMS:
I. NEUROLOGIC ASSESSMENT:
A clinical coma profile for bed side use
i. Verbal response:
a.None b.Incomprehensive
c.Confused e.Normal
ii. Eye opening:
a.None b.Noxious stimuli only
c.Verbal stimuli d.Spontaneous
iii. Pupils:
a.Non reactive b.Sluggish c.Brisk
iv. Oculo—cephalic ---oculovestibular reflexes
a.No reaction b.Partial or dysconjugate
3. LIVER FAILURE DR MAGDI AWAD SASI 2015
c.Full d.Normal
v. Best motor response:
a.None b.Abnormal extension
c.Abnormal flexsor d.With drawal or localize
e.Obeys commands
vi. Respiration :
a. Nil or ventilator b. Irregular
c. Regular > 22/ min d. Regular < 22 /min
Early hepatic encephalopathy produces varying degrees of bilateral forebrain dysfunction.
It is a reversible decrease in the conscious level in patients with sever liver disease.
Day to day changes in the score correlates well with improving or worsening outcomes.
The increased in nitrogenous waste "ammonia" passes to the brain and astrocytes take it up
with conversion of glutamate to glutamine shifting fluids into cells leading to cerebral edema
EEG PATTERN:
At the onset ----------slowing of the alpha rhythm
Increased drowsiness -------low frequency theta waves
Deep coma ----------high amplitude delta waves
Triphasic waves non specific for hepatic coma.
CEREBRAL OEDEMA:
Is a fatal complication in FHF with /without cerebellar /uncal herniation.
Difficult to predict in which condition develop and papillodema seldom present.
Bradycardia and hypotension are uncommon
STAGE I –
ALTERED BEHAVIOUR /MOOD
SLEEP DISTURBANCE
STAGE II—
INAPPROPRIATE BEHAVIOUR
GROSS DISORIENTATION
DROWSINESS/CONFUSION
SLOWNESS OF MENTATION
STAGE III
RESTLESSNESS
SLEEPING MOST OF TIME
INCOHERENT SPEECH
May occur in :
Reyes syndrome ---glial ,neuronal ,endothelial elements of brain swollen
Acetaminophin---- high intracerebral pressure
CT SCAN OF BRAIN NORMAL.
THE FIRST CLINICAL SIGN MAY BE SUDDEN RESPIRATORY ARREST ALONG WITH FIXED
DILATED PUPILS AND ABSENT BARIN STEM REFLEXES INDICATIVE TENTORIAL HERNIATION.
4. LIVER FAILURE DR MAGDI AWAD SASI 2015
TREATMENT
Lactulose 0.3 –0.4 ml/kg –10---50 ml/ 3 times
Vit K 5mg/kg for 3 days , prophylaxis 1mg /kg
Ranitidine 3mg/kg /24 hrs or omeprazole 40mg /d
2. RESPIRATORY DISORDERS :
Unexpected respiratory arrest may occur at any time of hepatic coma.
Once the gag reflex becomes depressed , the patients airway should be protected from
aspiration by ETT.
Hypoxia is another risk factor.
3.CARDIOVASCULAR DISORDERS:
Increased cardiac output is common.
Cardiac arrhythmia ---heart block ,bradycardia ,ventricular ectopy
This may result from :
i. Myocardial hypoxia
ii. Intracardiac pressure changes
iii. Changes in K level
Transient hypotension and central depression ocurr.
4. HYPOGLYCEMIA:
May cause deterioration in conscious level.
Caused by:
i. Lack of hepatic glycogen storage
ii. Lack of hepatic glucneogensis
iii. Increased anaerobic metabolism
5. COAGULATION DISORDER:
Defective hepatic protein synthesis affect coagulation ,fibrinolytic ,inhibitors of activated
factors.
Factor VII levels fall first.
Decreased factor V levels indicate that THE HEPATIC DAMAGE HAS OCCURRED
INDEPENDENT OF THE VIT K DEPENDENT FACTORS II ,VII ,IX ,X
Fibrinogen level fall last because liver preserve the synthesis untillfinal stage.
Factor VIII (( synthesized by vascular endothium )) fall in the final stages of FHF because of
the increased of catabolism.
DIC may occur ,not sever and caused by endotoxemia or transfusion of coagulation factors
6. GIT AND BLEEDING:
Erosive gastritis ----use H2 blocker
Tendency for bleeding:
i. DIC
ii. Abnormal platelet functions
iii. Thrombocytopenia
iv. Impaired synthesis of coagulation factors
v. Upper GIT –erosive
vi. Bleeding may occur.-----lung ,retroperitoneal ,epistaxis
NOTE:
HEPARIN IS C/I IN DIC
NO BENEFIT OF MULTIPLE TRANSFUSIONS
7. RENAL ,ELECTROLYTE ,ACID –BASE ABNORMALITIES:
5. LIVER FAILURE DR MAGDI AWAD SASI 2015
Electrolyte :
Hypokalemia ---common ,early stages ,life threatening
Hyponatremia ---high renal retention of Na and H2o
Hypernatremia ---large amounts of fresh frozen plasma
ACID---BASE
A. Respiratory alkalosis:
Thought to be of central origin and associated with:
i. Decreased o2 dissociation from HB
ii. Decreased cerebral and peripheral perfusion
iii. Decreased cerebral o2 consumption
B. METABOLIC ALKALOSIS:
Due to :
i. Hypokalemia
ii. Failure to alkalinze the urine
iii. Gastric aspiration
C. LACTIC ACIDOSIS:
With hypoglycemia due to increased catabolism & lack of gluconeogensis
Renal failure
Functional – characterized by intact renal tubules with low urine Na concentration
(< 10 m/l) , hyperosmolar urine ( U osm /Posm > 1: 10) and oliguria.
If require dialysis ; high rate of complications.
Hemodialysis ---GIT haemorrhage and hypotension -----due to heparin
Peritoneal dialysis ---- peritonitis and intraperitoneal hemorrhage
CORTICOSTEROIDS IN FHF:
Causes—
1. Significant increased blood urea concentration
2. Augmented protein catabolism in peripheral tissues
Increased liberation of nitrogenous products (ammonia) into the circulation
Incompletely converted to urea by failing liver with increased blood urea
Substrate for increased generation of ammonia in intestine
STEROIDS HAVE IMMUNOSUPPRESSIVE AND ULCEROGENIC
INCREASED RISK OF SEPSIS AND GIT BLEEDING
The corticosteroids are currently felt to be contraindicated in the management of
patient with FHF.
NUTRITION IN FHF:
Nutrional support is essential to prevent further injury to the liver cells
and progress to promote their generation.
Plasma aminoacids in FHF are not mainly derived from diet but result
from body protein catabolism and liver failure.
6. LIVER FAILURE DR MAGDI AWAD SASI 2015
Dietary protein must be given to replace oxidative looses.
Branched chain aminoacids ----
Decreased degradation of insulin by liver failure
This leads to high plasma insulin concentration with utilization of
BCAA by muscle
They are involved in the shuttling of the gluconeogenetic A.A.
(alanine &glutamine) to the intestinal mucosa and liver as energy
substrate.
They increased liver structural and secretory protein synthesis
and are anticatabolic -----improving nitrogen balance
-BCAA rich diet might improve both nutritional and neurological
condition in FHF.
PROTEIN FREE DIET IS CONTRAINDICATED.
HEPATIC ENCEPHALOPATHY SCALE
GRADE CRITERIA
0 No abnormality detected
1 Trivial lack of awareness, shortened attention span
2 Lethargy ,disorientation to time ,clear personality changes /behavior
3 Very drowsy, semicomatose but responsive to stimuli ,confused ,gross
deterioration in time or place , bizarre behavior.
4 Coma ,unresponsiveness to painful stimuli ,with /without abnormal
movements ,decorticate ,decerebrate posturing
ASTERIXIS
0 No flap
1 Rare flapping movement of fingers or hands
2 Occasional irregular flaps
3 Frequent flaps
4 Almost contains movement
FETOR
0 Absent
1 Moderate
2 Sever
TREATMENT OF FHF:
1. Admit to ICU
2. Head up tilt
3. Protect the air way with intubation
4. Insert an NGT to avoid aspiration ,remove blood from stomach
5. Insert urinary/CVL to asses fluid
6. Monitor vital signs ----BP ,PR ,TEMP ,UOP hourly ,daily weights
7. Check FBS ,LFT ,RFT ,INR ,ELECTROLYTES daily
8. 10% dextrose 1L/12 HR to avoid hypoglycemia
9. Treat the cause -----paracetamol?
10. If malnourished ,good nutrition ---thiamine ,folate
11. Hemofitration and hemodialysis
12. Avoid sedation -----use Lorazepam
13. Use Omeprazole
14. Cover by antibiotics ----ceftriaxone
7. LIVER FAILURE DR MAGDI AWAD SASI 2015
KEEP IN MIND ,WE ARE TRYING TO TREAT:
BLEEDING ,INFECTION, ENCEPHALOPATHY ,HYPOGLYCEMIA ,ASCITES
POOR PROGNOSTIC FACTORS:
1. Age above 40 years
2. Albumin less than 30gm/l
3. Grade III/ VI
4. Increased INR
5. Drug induced liver failure
6. Late onset hepatic failure
LIVER TRANSPLANTATION:
INDICATION---
1) Alcoholic liver disease
2) HBV and HCV
3) Primary biliary cirrhosis
4) Primary sclerosing cholangitis
5) Alpha one antitrypsin deficiency
6) Hemochromatosis
7) Wilsons disease
8) Autoimmune hepatitis
9) HCC 3 nodules < 3cm , 1 nodule < 5 cm
POST TRANSPLANT:
1. Prednisolone
2. Ciclosporin /tacrolimus
3. Azathioprine /mycophenolate mofetil
HYPER ACUTE REJECTION(( T cell mediated )):
50% of cases 5 –10 days after O.T.
Patients complain of feeling unwell ,pyrexia, render hepatomegally
Complications:
1) Sepsis
2) Hepatic artery tgrombosis
3) CMV infection
Chronic rejection 6—9 months
H.H.
S&S Of iron over load + F/H of H.H. -------- CLINICAL SUSPECION OF HH
