Hepatic failure can be acute or chronic and results from the liver's inability to perform normal functions. Acute hepatic failure progresses rapidly over weeks while chronic failure occurs over months to years. Common causes include viral hepatitis, alcohol abuse, and cirrhosis. Complications include encephalopathy, coagulopathy, and multi-organ failure. Prognosis depends on the underlying cause and ranges from recovery with acute cases to death within weeks to months with chronic cases without transplantation.

1. Hepatic
Failure
Lecture18 n
Dr Mohammad Manzoor Mashwani BKMC Mardan
Clinical Syndromes of Liver Diseases

2. HEPATIC CLINICAL SYNDROMES
The major clinical syndromes of liver disease are:
Hepatic failure,
Cirrhosis,
Portal hypertension,
Cholestasis

3. Definition of Liver Failure
Liver failure is the inability of the liver to perform
its normal synthetic and metabolic function as part of normal physiology.
Two forms are recognized, acute and chronic.
80% to 90% of hepatic function must be lost before hepatic failure ensues.
•A course expending as long as 3 months is called subacute failure.
liver has a marked regenerative capacity and a large
functional reserve,

4. Liver Functions
1. Manufacture and excretion of BILE.
2. Manufacture of several major plasma proteins
such as albumin, fibrinogen and prothrombin.
3. Metabolism of proteins, carbohydrates and lipids.
4. Storage of vitamins (A, D and B12) and iron.
5. Detoxification of toxic substances such as alcohol
and drugs.

5. The alterations that cause liver failure
fall into three categories:
• 1. Acute liver failure with massive hepatic necrosis
• 2. Chronic liver disease
• 3. Hepatic dysfunction without covert necrosis

6. I. Acute Hepatic Failure (ALF)
• Acute hepatic failure is defined as "the rapid
development of hepatocellular dysfunction,
specifically coagulopathy and mental status changes
(encephalopathy ) in a patient without known prior liver disease".
Caused by drugs or fulminant (sudden & severe, thundering) viral hepatitis
ALF denotes clinical hepatic insufficiency that progresses from onset of
symptoms to hepatic encephalopathy within 2 to 3 weeks.
Morphology : Massive hepatic necrosis.

8. •Hepatotoxic drug reactions
( anaesthetic agents,NSAIDs, anti-depressants),
•carbon tetrachloride poisoning,
•pregnancy complicated with eclampsia.

9. ii. cHronic Hepatic Failure (CLF)
• Chronic hepatic failure usually occurs in the context
of cirrhosis.
This is the most common route to hepatic failure and is the end point of
relentless (persistent) chronic liver damage ending in cirrhosis.
where the liver fails over months to years

10. Causes of CLF
The most common causes of chronic liver failure include:
• Hepatitis B
• Hepatitis C
• Long term alcohol consumption
• Cirrhosis
• Hemochromatosis (an inherited disorder that causes the body
to absorb and store too much iron)
• Malnutrition
chronic active hepatitis,
Chronic cholestasis (cholestatic jaundice)
Wilson’s disease

11. III. Hepatic dysfunction without overt necrosis
• Hepatocytes may be viable but unable to
perform normal metabolic function,
Causes:
Tetracycline toxicity, and
Reye syndrome.
.

12. REYE’S SYNDROME
• Reye’s syndrome is defined as an acute postviral syndrome of encephalopathy and
fatty change in the viscera. The syndrome may follow almost any known viral
disease but is most common after influenza A or B and varicella. Viral infection may
act singly, but more often its effect is modified by certain exogenous factors such
as by administration of salicylates, aflatoxins (mycotoxins) and insecticides. These
effects cause mitochondrial injury and decreased activity of mitochondrial
enzymes in the liver. This eventually leads to rise in blood ammonia and
accumulation of triglycerides within hepatocytes. The patients are generally
children between 6 months and 15 years of age. Within a week after a viral illness,
the child develops intractable vomiting and progressive neurological deterioration
due to encephalopathy, eventually leading to stupor, coma and death.
Characteristic laboratory findings are elevated blood ammonia, serum
transaminases, bilirubin and prolonged prothrombin time.
MORPHOLOGIC FEATURES. Grossly, the liver is enlarged and yellowish-orange.
Microscopically, hepatocytes show small droplets of neutral fat in their cytoplasm (microvesicular fat). Similar fatty change
is seen in the renal tubular epithelium and in the cells of skeletal muscles and heart. The brain shows oedema and
sometimes focal necrosis of neurons.
The first description of this syndrome was probably made by Najib Khan in Jamshedpur
in 1956 (Jamshedpur fever).[

13. Types ABC
• Type A (=acute) describes hepatic encephalopathy
associated with acute liver failure, typically
associated with cerebral oedema
• Type B (=bypass) is caused by portal-systemic
shunting without associated intrinsic liver disease.
• Type C (=cirrhosis) occurs in patients with cirrhosis -
this type is subdivided in episodic, persistent and
minimal encephalopathy
A portosystemic shunt (PSS), also known as a liver shunt,
is a bypass of the liver by the body's circulatory system.

14. Clinical features
• Jaundice and cholestasis
• Hypoalbuminemia
• Hypoglycemia
• Palmar erythema
• Spider angioma
• Hypogonadism
• Gynecomastia
• Weight loss
• Muscle wasting
Early symptoms:
Nausea
Loss of appetite
Fatigue
Diarrhea
Serious Symptoms
Jaundice
Bleeding easily
Swollen abdomen
Mental disorientation or confusion (known as hepatic
encephalopathy)
Sleepiness
Coma
Jaundice usually reflects the severity of liver cell damage
since it occurs due to failure of liver cells to metabolise
bilirubin. In acute failure such as in viral hepatitis,
jaundice nearly parallels the extent of liver cell damage,
while in chronic failure such as in cirrhosis jaundice
appears late and is usually of mild degree.

15. Complications of Hepatic Failure
• Failure of multiple organ systems
• Coagulopathy
• Hepatic encephalopathy (Hepatic Coma)
• Hepatorenal syndrome
Hepatic encephalopathy: disturbed consciousness, personality changes, intellectual
deterioration, low slurred speech, flapping tremors, and finally, coma and death.

17. Prognosis
In chronic liver disease death occurring within
weeks to a few months in about 80% of cases.
About 40% of patients with acute liver failure may
recover spontaneously.
Liver transplantation in acute or chronic liver failure
can be curative.

18. Hepatic encephalopathy
• Hepatic encephalopathy (also known as
portosystemic encephalopathy) is the occurrence
of confusion, altered level of consciousness, and
coma as a result of liver failure. In the advanced
stages it is called hepatic coma or coma hepaticum.
It may ultimately lead to death.

19. Hepatic encephalopathy may develop rapidly in acute liver
failure or insidiously with gradually evolving chronic liver
failure from cirrhosis.
In either setting, patients with hepatic encephalopathy show
a spectrum of brain dysfunction ranging from subtle
behavioral abnormalities to marked confusion and stupor,
to deep coma and death.
These changes may progress over hours or days as, for
example, in fulminant hepatic failure or gradually in a
person with marginal hepatic function from chronic liver
disease.

20. Associated fluctuating neurologic signs include rigidity, hyperreflexia,
nonspecific electroencephalographic changes, and, rarely, seizures.
Particularly characteristic is asterixis (also called flapping
tremor or liver flap),
which is a pattern of nonrhythmic, rapid extensionflexion
movements of the head and extremities, best seen
when the arms are held in extension with dorsiflexed wrists.
Asterixis- a recurrent flapping tremor of the arms, like the action of a bird's wings,
that occurs as a result of a brain condition associated with liver failure
The tremor is caused by abnormal function of the diencephalic motor centers in
the brain, which regulate the muscles involved in maintaining position.
The term derives from the Greek a, "not" and stērixis, "fixed position".

21. Signs & symptoms
•Forgetfulness,
•Mild confusion,
• Irritability and
•Coma.
Disturbed consciousness,
personality changes,
intellectual deterioration,
low slurred speech,
flapping tremors, and
finally, coma and
death.

22. • Hyperkinetic circulation. All forms of hepatic failure
are associated with a hyperkinetic circulation
characterised by peripheral vasodilatation,
increased splanchnic blood flow and increased
cardiac output. There is increased splenic flow
but reduced renal blood flow resulting in impaired
renal cortical perfusion. These changes result in
tachycardia, low blood pressure and reduced renal
function.

23. Morphology
• In most instances there are only minor morphologic
changes in the brain, such as edemaand an
astrocytic reaction.

24. Two factors seem to be important in the genesis of this disorder:
•1. Severe loss of hepatocellular function
•2. Shunting of blood from portal to systemic
circulation around the chronically diseased liver.

25. In the acute setting, an elevation in blood ammonia,
which impairs neuronal function and promotes generalized
brain edema, seems to be key.
In the chronic setting, deranged neurotransmitter production,
particularly in monoaminergic, opioidergic, γ-aminobutyric
acid (GABA)-ergic, and endocannabanoid systems, leads to
neuronal dysfunction.
The genesis of CNS manifestations in liver disease is by toxic products not
metabolised by the diseased liver. The toxic products may be ammonia and other
nitrogenous substances from intestinal bacteria which reach the systemic
circulation without detoxification in the damaged liver and thus damage the
brain..

26. Hepatic encephalopathy West Haven Criteria
• Grade 1 - Trivial lack of awareness; euphoria or anxiety;
shortened attention span; impaired performance of
addition or subtraction
• Grade 2 - Lethargy or apathy; minimal disorientation
for time or place; subtle personality change;
inappropriate behaviour
• Grade 3 - Somnolence to semi stupor, but responsive
to verbal stimuli; confusion; gross disorientation
• Grade 4 - Coma (unresponsive to verbal or noxious
stimuli)

27. Other signs & symptoms
• Jaundice,
• Ascites,
• Peripheral oedema.
• Tendon reflexes exaggerated,
• Babinski's sign positive
• Foetor hepaticus

28. Hepatic encephalopathy- Causes
• Liver failure,
• Large amount of protein consumption,
• GIT bleeding,
• Renal failure,
• Constipation,
• Hyponatremia,
• Hypokalemia,
• Alkalosis,
• Hypoxia,
• Dehydration,
• Sedatives, narcotics, alcohol intoxication,
• Surgery,
• Unknown (2o-3o%).

29. Hepatorenal syndrome
• Patients of (both acute and chronic) hepatic failure who
develop renal failure as well, in the absence of
clinical, laboratory or morphologic evidence of
other causes of renal dysfunction.
• Hepatorenal syndrome develops in about 10%
cases of acute and chronic liver diseases.
Kidney function promptly improves (reversible ) if
hepatic failure is reversed.

30. Etiology• Splanchnic vasodilation &
• systemic vasoconstriction,
leading to severe reduction of renal blood flow.
The pathogenesis of the syndrome is poorly understood but appears to be
initiated by effective reduction of the renal blood flow (effective hypovolaemia) as
a consequence of systemic vasodilatation and pooling of blood
in portal circulation.

31. Clinical features
• Drop in urine output, associated with rising blood
urea nitrogen and creatinine values.
• The renal failure may hasten death in the
patient with acute fulminant or advanced chronic
hepatic disease.
• Alternatively, borderline renal insufficiency may
persist for weeks to months.
The acute renal failure is usually associated with oliguria and uraemia but
with good tubular function.

32. Hepatopulmonary syndrome.
The pulmonary changes in chronic hepatic failure
such as in cirrhosis consist of pulmonary
vasodilatation with intra-pulmonary arteriovenous
shunting. This results in ventilation-perfusion
inequality that may lead to impaired pulmonary
function, clubbing of fingers and sometimes
cyanosis.

33. Coagulation defects
Impaired synthesis of a number of coagulation
factors by the diseased liver may result in
coagulation disorders. These include disseminated
intravascular coagulation (consumption coagulopathy),
thrombocytopenia and presence of fibrin
degradation products in the blood.

34. Ascites and oedema
Chronic liver failure due to cirrhosis may result in
portal hypertension and ascites.
Decreased synthesis of albumin by the liver resulting
in hypoproteinaemia and consequent fall in
plasma oncotic pressure, increased hydrostatic
pressure due to portal hypertension and
secondary hyperaldosteronism, contribute to the
development of ascites and oedema in these
patients.

35. Endocrine changes
The changes are more common in alcoholic cirrhosis
in active reproductive life. In the male, the
changes are towards feminisation such as
gynaecomastia and hypogonadism. In the female,
the changes are less towards masculinisation but
atrophy of gonads and breasts occurs. The
underlying mechanism appears to be changed end-
organ sensitiveness to sex hormones in cirrhosis.

36. Skin changes
In alcoholic cirrhosis ‘arterial spiders’ having
radiating small vessels from a central arteriole are
frequent in the vascular region drained by superior
vena cava such as in the neck, face, forearms and
dorsum of hands.
• Less frequently, palmar erythema, especially in the
hypothenar and thenar eminences and on the
pulps of the fingers, is observed in chronic liver
disease.

37. Foetor hepaticus
A sweetish pungent smell of the breath
is found in severe cases of acute and chronic
hepatocellular diseases. It appears to be of
intestinal origin, possibly due to failure of the liver
to detoxify sulfur-containing substances absorbed
from the gut.