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

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

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.

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:

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.

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

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