SudaMediCa, The Sudanese Medical Community

First (olfactory) nerve
Causes of anosmia:
Bilateral:
1. Upper respiratory tract infection( commonest)
2. Meningioma of the olfactory groove(late)
3. Ethmoid tumour
4. Head trauma (including cribriform plate fracture)
5. Meningitis
6. Hydrocephalus
7. Congenital-Kallmann,s syndrome(hypogonadotrophic hypogonadism)
Unilateral:
1. Meningioma of the olfactory groove (early)
2. Head trauma
How to examine?
Series of sample bottles containing vanilla, coffee or other non irritant substances. Remember to test each nostril separately.

Second ( optic) nerve:
Light reflex
Constriction of the pupil in response to light is relayed via the optic nerve and tract, the superior quadrigeminal brachium, the Edinger-Westphal nucleus and its efferent sympathetic fibers in the third nerves.
Acommodation reflex:
Constriction of the pupil with accommodation originates in the cortex ( in association with convergence) and is relayed via the sympathetic fibers in the third nerve.
Causes of absent light reflex but intact accommodation reflex:
1) Midbrain lesion(e.gArgyll Robertson pupil)
2) Ciliary ganglion lesion(e.g Adie,s pupil)
3) Parinaud,s syndrome
4) Bilateral anterior visual pathway lesions( i.e bilateral afferent pupil deficits)
Causes of absent convergence but intact light reflex
Cortical lesion(e.g cortical blindness).
Visual field defects
1. TUNNEL VISION:concentric diminution( glaucoma, papilloedema, syphilis).
2. ENLARGED BLIN SPOT: optic nerve head enlargement.
3. CENTRAL SCOTOMA: optic nerve head to chiasmal lesion( e.g demyelination, toxic, vascular, nutritional)
4. UNILATERAL VISUAL FIELD LOSS: optic nerve lesion( e.g. vascular, tumour)
5. BITEMPORAL HEMIANOPIA: optic chiasmal lesion( e.g pituitary tumor, sella meningioma)
6. HOMONYMOUS HEMIANOPIA: optic tract to occipital cortex, lesion at any point ( e.g vascular, tumour. Note : Incomplete lesion results in macular sparing.
7. UPPER QUADRANT HOMONYMOUS HEMIANOPIA: temporal lobe lesion (e.g vascular or tumour)
8. LOWER QUADRANT HOMONYMOUS HEMIANOPIA:parietal lobe lesion.
Pupil abnormalities
Causes of constriction
1. Horner,s syndrome
2. Argyll Robertson pupil.
3. Pontine lesion( often bilateral but reactive to light).
4. Narcotics
5. Pilocarpine drops
6. Old age
Causes of dilatation:
1. Mydriatics, atropine poisoning or cocaine.
2. Third nerve lesion
3. Adie,s pupil
4. Post trauma, deep coma ,cerebral death
5. Congenital
How to examine second ( optic ) nerve?
Test visual acuity ( with the patient spectacles on, as refractive errors are not cranial nerve abnormalities) using a visual a cuity chart. Test each eye separately, covering the other eye with a small card.
Examine the visual fields by confrontation using a red-tipped hatpin, making sure your head is level with the patient,s head. A red hatpin enables you to detect earlier peripheral field loss. Test each eye separately. If the patient has such poor acuity that hatpin is difficult to use, map the fields with your fingers. When you are testing his right eye, he should look straight in to your left eye. His head should be at arm,s length and should cover the eye not being tested with his hand. Bring the hatpin from the four main directions diagonally towards the centre of the field of vision.
Next map out the blind spot by asking about disappearance of the hatpin lateral to the centre of the field of vision of each eye. A gross enlargement may be detectable by comparison with your own blind spot.
Look in to fundi
Holmes-Adie syndrome
Cause
Lesion in the efferent parasympathetic pathway
Signs:
1. Dilated pupil
2. Decreased or absent reaction to light( direct and consensual)
3. Slow or incomplete reaction to accommodation with slow dilation afterwards.
4. Decreased tendon reflexes
5. The patients are commonly young women
6. Denervation supersensitivity to a weak (e.g 0.125%) pilocarpine solution.
Argyll Robertson pupil
Cause
Lesion of irridodilator fibres in the midbrain, as in:
1. Syphilis
2. Diabetes mellitus
3. Alcoholic midbrain degeneration( rarely)
4. Other midbrain lesions
Signs
1. Small irregular, unequal pupil
2. No reaction to light
3. Prompt reaction to light
4. If tabes associated, decreased reflexes
5. Some mydriatics( e.g.atropine, cocaine) dilate slowly. Direct sympathetic agonists dilate promptly

Causes of papilloedema:
1. Space-occupying lesion (causing raised intracranial pressure) or a retro-orbital mass.
2. Hydrocephalus ( associated with large ventricles)
3. Idiopathic intracranial hypertension
4. Hypertension (grade 1V)
5. Central retinal vein thrombosis
6. Cerebral venous sinus thrombosis
7. High cerebrospinal fluid protein level-Guillain-Barre syndrome
Causes of optic atrophy:
1. Chronic papilloedema or optic neuritis
2. Optic nerve pressure or division
3. Glaucoma
4. Ischaemia
5. Familial- retinitis pigmentosa, leber,s disease, Friedreich,s ataxia.
Causes of ptosis
1- With normal pupils:
 Myasthenia gravis
 Myotonic dystrophy
 Fascioscapulohumeral dystrophy
 Ocular myopathy
 Thyrotoxic myopathy
 Senile ptosis
 Botulism, snake bite
 Congenital
 Fatigue
2-With constricted pupils:
 Horner syndrome
 Tabes dorsalis
2- With dilated pupil:
Third nerve lesion







Third ( occulomotor) nerve
Clinical features of a third cranial nerve palsy
1. Complete ptosis ( partial ptosis may occur with an incomplete lesion).
2. Divergent strabismus( eye down and out)
3. Dilated pupil unreactive to direct or consensual light and unreactive to accommodation
Aetiology:
Central
1. Vascular (e.g. brain stem infarction).
2. Tumour.
3. Demyelination ( rare)
4. Trauma
5. Idiopathic
Peripheral
1. Compressive lesions:
a) Aneurysm(usually on the posterior communicating artery).
b) Tumour causing raised intracranial pressure
c) Nasopharyngeal carcinoma
d) Orbital lesions-Tolosa-Hunt syndrome( superior orbital fissure syndrome-painful lesion of the third, fourth, sixth and the first division of the fifth cranial nerve)
e) Basal meningitis
2. Infarction-diabetes mellitus, arteritis ( pupil is usually spared)
3. Trauma
4. Cavernous sinus thrombosis
Sixth (abducens) nerve
Clinical features of a sixth nerve palsy
1. Failure of lateral movement
2. Affected eye is deviated inwards in severe lesions.
3. Diplopia-maximal on looking to the affected side. The images are horizontal and parallel to each other. The outermost image is from the affected eye and disappears on covering this eye( the image is usually more blurred)
Aetiology:
Bilateral
1. Trauma( head injury)
2. Wernicke,s encephalopathy
3. Raised intracranial pressure
4. Mononeuritis multiplex
Unilateral
1.central:
a) Vascular
b) Tumour
c) Wernickes encephalopathy
d) Multiple sclerosis ( rare)
3- Peripheral:
a) Diabetes
b) Trauma
c) Idiopathic
d) Raised intracranial pressure
Eye movement:
With the eye abducted: the elevator is the superior rectus( third nerve). The depressor is the inferior rectus( third nerve). With the eye adducted: the elevator is the inferior oblique( third nerve). The depressor is the superior oblique( fourth nerve).
Examination of third, fourth and sixth nerves:
Look at the pupils. Note the shape, relative sizes and any associated ptosis. Use your pocket torch and shine the light from the side to gauge the reaction to light on both sides. Practise assessing the direct and consensual responses rapidly.
Look for the Marcus Gunn phenomenon ( afferent papillary defect) by moving the torch in an arc from pupil to pupil. The affected pupil will paradoxically dilate after short time when the torch is moved from a normal eye to one with optic atrophy or very decreased visual acuity from other causes. Test accommodation by asking the patient to look in to the distance and then at your red hatpin placed about 15cm from his nose.
Assess eye movements with both eyes first. Ask the patient to look voluntarily and then follow the red hatpin In each direction-right and left lateral gaze, plus up and down in the lateral position. Look for failure of movement and nystagmus. Ask about diplopia when eyes are in each position. With complex lesions then assess each eye separately. Move the patient,s head if the patient is unable to follow movements.



Fifth nerve:
Ask permission first to test the corneal reflexes. Make sure you touch the cornea( not the conjunctiva) gently with a peace of cotton wool. Come in from the side and do this only once on each side. If the nerve pathways are intact, the patient will blink both eyes. Ask him wether he can actually feel the touch (V is the sensory component).
Note :With an ipsilateral seventh nerve palsy, only the contralateral eye will blink- sensation is preserved( nerveV11 is the motor component).Also with an ipsilateral seventh nerve palsy, the eye on the side of the lesion may roll superiorly with corneal stimulus (Bell,s phenomenon).
Test facial sensation in the three divisions:ophthalmic, maxillary and mandibular. Use a pin first to assess pain. Map out any area of sensory loss from dull to sharp and check for any loss up on the posterior part of the head(C2) and neck (C3). Light touch must be tested also, as there may be sensory dissociation.
Note: A medullary or upper cervical lesion of the fifth nerve causes loss of pain and temperature sensation with preservation of light touch. A pontine lesion may cause loss of light touch with preservation of pain and temperature sensation.
Examine the motor division by asking the patient to clench his teeth( feeling the masseter muscles) and open his mouth;the pterigoid muscles will not allow you to force it closed if the nerve is intact. A unilateral lesion causes the jaw to deviate towards the weak ( affected ) side.
Always test the jaw jerk (with the mouth just open, the finger over the jaw is tapped with a tendon hammer).
Seventh cranial nerve:
Aetiology:
Upper motor neurone lesion( supranuclear)
1. Vascular
2. Tumour
Lower motor neurone lesion
Pontine ( often associated with nerves V,V1 )
1. Vascular
2. Tumour
3. Syringobulbia
4. Multiple sclerosis
Posterior fossa
1. Acoustic neuroma
2. Meningioma
Petrous temporal bone
1. Bell,s palsy
2. Ramsy Hunt syndrome
3. Otitis media
4. Fracture
Parotid
1. Tumour
2. Sarcoid
Causes of bilateral lower motor neurone facial weakness:
1. Guillain-Barre syndrome
2. Bilateral parotid disease ( sarcoid)
3. Mononeuritis multiplex )( rare)
Note: Myopathy and neuromuscular junction defects can also cause bilateral facial weakness.
Examination of seventh nerve:
Look for facial asymmetry and then test the muscles of facial expression. Ask the patient to look up and wrinkle his forehead. Look for loss of wrinkling and feel the muscle strength by pushing down on each side. This is preserved in an upper motor neurone lesion because of bilateral cortical representation of these muscles.
Next ask the patient to shut his eyes tight-compare how deeply the eyelashes are buried on the tow sides and then try to open each eye. Tell him to grin and compare the nasolabial grooves.
If a lower motor neurone lesion is detected, quickly check for ear and palatal vesicles of herpes zoster of the geniculate ganglion- the Ramsy Hunt syndrome.
Examining for taste on the anterior tow-thirds of the tongue is not usually required.
Eighth (acoustic) nerve:
To differentiate nerve deafness from conductive deafness, use the following tests.
Rinne,s test
A 256-Hertz vibrating tuning fork is first placed on the mastoid process, behind the ear, when the sound is no longer heard,it is placed in line with the external meatus.

Results:
1. Normal-the note is audible at the external meatus.
2. Nerve deafness-the note is audible at the external meatus as air and bone conduction are reduced equally, so that air conduction is better ( as is normal). Positive result.
3. Conduction(middle ear) deafness-no note is audible at the external meatus. Negative result.
Weber,s test:
A 256-Hertz running fork is placed on the centre of the forehead.
Results:
1. Normal-the sound is heard in the centre of the forehead.
2. Nerve deafness-the sound is transmitted to the normal ear.
3. Conduction deafness-the sound is heard louder in the abnormal ear
Note :A lthoughof traditional importance, these tests are not very accurate and are now rarely used by neurologists.
Causes of deafness
Nerve ( sensorineural) deafness:
1. Degeneration
2. Trauma (e.g high noise exposure, fracture of the petrous temporal bone)
3. Toxic( e.g aspirin, alcohol, streptomycin)
4. Infection (e.g. congenital rubella syndrome, congenital syphilis)
5. Tumour (e.g. acoustic neuroma).
6. Brain stem lesion.
7. Vascular disease of the internal auditory artery.
Conductive deafness:
1. Wax.
2. Otitis media.
3. Otosclerosis
4. Paget,s disease of bone
Ninth (glossopharyngeal ) and tenth (vagus) nerve palsy:
Aetiology:


Central:
1. Vascular (e.g.lateral medullary infarction owing to vertebral or posterior inferior cerebellar artery disease)
2. Tumour.
3. Syringobulbia.
4. Motor neuron disease (vagus nerve only)
Peripheral-posterior fossa
1. Aneurysm.
2. Tumour.
3. Chronic meningitis
4. Guillain-Barre syndrome(vagus nerve only)
Examination of the ninth and tenth nerve:
Look at the palate and note any uvular displacement. Ask the patient to say (aaah) and look for asymmetrical movement of the soft palate. With a unilateral tenth nerve lesion the uvula is drawn towards the unaffected (normal) side.
Testing the gag reflex is traditional butadds little to the examination.Ask the patient to speak ( to assess hoarseness) and to cough ( listen for a bovine cough, which may occur with a recurrent laryngealnerve lesion).
Eleventh nerve:
Ask the patient to shrug his shoulders and then the trapezius bulk and push the shoulders down. Then instruct the patient to turn his head against resistance(your hand) and also feel the muscle bulk of the sternomastoids.
Twelfth(hypoglossal) nerve palsy:
Aetiology
Upper motor neurone lesion
1) Vascular.
2) Motor neurone disease.
3) Tumour
4) Multiple sclerosis.
Note: The syndrome of bilateral upper motor neurone lesions of the ninth, tenth and twelfth nerves is called pseudobulbar palsy.

Lower motor neurone lesion-unilateral:
Note: It is difficult to detect unilateral lesions as the tongue muscles ( except the genioglossus) are bilaterally innervated.
Central:
1) Vascular-thrombosis of the vertebral artery.
2) Motor neurone disease
3) Syringobulbia.
Peripheral( Posterior fossa):
1) Aneurysm.
2) Tumour.
3) Chronic meningitis.
4) Trauma.
5) Arnold-Chiari malformation of the base of the skull.
Note;The Arnold-Chiari malformation is a protusion of the cerebellar tonsils through the foramen magnum. The more severe types (11-1V) cause basilar compression with lower cranial nervepalsies, cerebellar limb signs( owing to tonsillar compression) and upper motor neurone signs in the legs.
Lower motor neurone lesion-bilateral
1. Motor neurone disease.
2. Arnold-Chiari malformation
3. Guillain-Barre syndrome
4. Polio.
Examination of the twelfth nerve:
While examining the mouth, inspect the tongue for wasting and fasciculation( bet seen with the tongue not protruded and which may be unilateral or bilateral). Next ask the patient to protrude his tongue. With a unilateral lesion the tongue deviates towards the weaker side.
Causes of multiple cranial nerve palsies:
Think of cancer first.
1) Nasopharyngeal carcinoma.
2) Chronic meningitis.(e.g.carcinoma,tuberculosis,sarcoidosis)
3) Guillain-Barre syndrome( spares nerves 1,11 andV111), including the Miller-Fisher variant.
4) Brain stem lesion.
5) Arnold-Chiari malformation.
6) Trauma
7) Lesion of the base of the skull( e.g. Paget disease, large meningioma, metastasis).
8) Mononeuritis multiplex, rarely (e.g. diabetes mellitus).

Chronic liver disease is liver damage occurring for more than 6 months. It results in progressive fibrosis and eventually cirrhosis. Cirrhosis comprises fibrotic liver damage with regenerative nodule formation, and consequent portal hypertension.
Causes of chronic progressive liver disease are:
Chronic viral hepatitis( hepatitis B,delta, C)- The damage is most likely due to immune mediated mechanisms rather a viral cytopathic effect.
Alcohol- induced liver disease
Non-alcoholic steatohepatitis ( NASH)
Genetic haemochromatosis-Excess iron absorption from the intestine results in accumulation in hepatocytes, hepatocytes necrosis and cirrhosis.
Autoimmune liver disease-Immune cell infiltration and hepatocytes damage leads to rapidly progressive fibrosis and cirrhosis.
Primary biliary cirrhosis.
Secondary biliary cirrhosis
Primary sclerosing cholangitis.
Alpha1-antitrypsin deficiency-Abnormal protein cannot be adequately exported from hepatocytes, where accumulates causing hepatocytes damage.
Wilson,s disease-Abnormalities in the biliary copper transporter results in excess copper accumulation in the liver and brain,with hepatocytes damage and basal ganglia disease. The disease is geneticall, heterogeneous and this is reflected in variable clinical presentation ( e.g.rapid neurological deterioration, early onset fulminant liver failure, or chronic liver disease presenting with cirrhosis).
Drug induced ( methyl dopa, nitrofurantoin, isoniazid, chlorpromazine, propylthiouracil, methotrexate, amiodarone)
Cystic fibrosis
Budd-CHiari syndrome
Cardiac failure, chronic constrictive pericarditis
Cryptogenic (Idiopathic).
Epidemiology:
Incidence varies with geographic region, age and sex. The commonest cause of chronic hepatitis in the world is hepatitis C. In the UK the commonest cause of cirrhosis is alcohol, followed by hepatitis C.
Hepatitis C: Is an RNAvirus that is parenterally transmitted. The majority of those infected develop hepatitis 14-160 days after exposure.Prodromal symptoms are fever and malaise,jaundice is rare, and the vast majority are asymptomatic. Fifty percent recover completely, but 50% go on to develop persistant viraemia and slowly progressive chronic liver disease,passing in the course of 20-40 years from acute to chronic persistent hepatitis, to chronic active hepatitis, to cirrhosis( in 10%) and eventually hepatocellular carcinoma.
Clinical presentation:
Common
Non-specific malaise, loss of lipido,mental changes. Hepatic decompensation:jaundice, ascites, hepatic encephalopathy, variceal haemorrhage. Most patients with chronic liver disease are asymptomatic until cirrhosis develops. It is also possible to be asymptomatic in the presence of cirrhosis if portal hypertension has not developed.
The history:
1-Ask about length of history of liver disease:
a) Past history of hepatitis or jaundice, including contact.
b) Alcohol intake (in men 80 g per day for more than 10 years is usually necessary; women need less exposure)
c) History of drug addiction( intravenous),sexual preference,transfusions,tattoos etc.
d) Drug history
e) History of diabetes mellitus, cardiac failure or arthropathy( haemochromatosis)
2-Ask about treatment( e.g. protein restriction, fluid restriction, alcohol abstinence, steroid, lactulose, neomycin)
3-Ask about complications, such as any history of encephalopathy, any history of portal hypertension( ascites or bleeding from varices)
4-Ask about investigations( e.g.liver biopsy)
5-Ask about operations ( e.g.portacaval shunt)
6-Ask about erectile dysfunction, loss of lipido.
7-Inquire about social problems( e.g.employment, family)
The examination:
General signs of chronic liver disease:
These may include:
• Jaundice
• Scratch mark secondary to itch
• Palor/anaemia
• Cyanosis( due to pulmonary venous shunting
• Purpura
• Spider naevi
• Gynaecomastia
• Paucity of body hair
• Testicular atrophy
• Muscle wasting
• In the hand , you may find clubbing, Duputren,s contracture, palmar erythema, leuconychia, muscle wasting.
• Hepatomegaly ( in cirrhosis the liver may be small or large and nodular due to regeneration. It may alsobe enlarged by acute inflammation)
General signs of hepatic decompensation:
Hepatic decompensation can occur in both chronic and acute liver disease.
The main signs are:
 Jaundice
 Evidence of hepatic encephalopathy(e.g. asterixis)
 Ascites
 Evidence of bleeding( e.g. purpura)
Signs which suggest an underlying cause:
 Dupuytren,s contracture Alcohol
 Parotid hypertrophy

 Tattoos
 Track marks Viral hepatitis

 Signs of associated autoimmune disease- autoimmune hepatitis
 Xanthelasma-PPBC
 Slate grey pigmentation- haemochromatosis
 Kayser- Fleischer rings-Wilson disease
 Signs of obstructive airways disease-alpha-1 antitrypsin defeciency
Sequelae of cirrhosis:
1) Portal hypertension and ascites
2) Spontaneous bacterial peritonitis
3) Hepatic encephalopathy
4) Heptorenal syndrome
5) Hepatocellular carcinoma
6) Portal vein thrombosis ( rare)

Portal hypertension :
The portal vein enters the liver at the porta-hepatis and sends a branch to each lobe. It receives blood from all veins draining the abdominal part of the gastrointestinal tract and is formed from union of the superior mesenteric vein and the splenic vein. Normal portal flow rate is about 1-1.5 L/min with a pressure of 5-10 mmHg.
When portal flow is obstructed , either from within or without the liver,collateral circulation develops to carry blood into systemic veins( portosystemic shunt). Tow problem then arise:
1. The liver,s metabolic function is bypassed
2. Increasing pressure in collaterals( termed varices) causes bleeding.
Varices are commonly oesophageal, derived from the left gastric vein. There are multiple layers of veins in the oesophagus and varices usually develop in the deep intrinsic layer. Varices occur at the other sites including the stomach,colon and rectum.
Hyperdynamic circulation accompanies portal hypertension and may in part develop to maintain portal flow as collaterals lower the blood pressure.
Clinical consequences of portal hypertension:
1. Gastrointestinal bleeding, often the first indication of varices.
2. Caput medusa
3. Venous hum
4. Splenomegaly (but size correlates poorly with portal pressure)
5. Secondary hypersplenism ( can cause peripheral blood cytopenias)
Ascites
Mechanism of ascites:
Over 75% of ascites is due to liver disease. The pathogenesis is uncertain but contributing factors include hypoalbuminaemia and portal hypertension. It is also likely that peripheral vasodilatation promotes sodium and water retension by stimulating the renin-angiotensin-aldosterone system.
Look for/consider causes:
1. Chronic liver disease/ cirrhosis: look for signs of chronic liver disease.
2. Malignancy( especially gastric,ovarian and liver metastases): look for cachexia and lymphadenopathy.
3. Right/biventricular failure: look for a raised JVP and peripheral oedema
4. Nephrotic syndrome and other cause of hypoalbuminaemia( check the urinalysis)
5. Rare causes include hypothyroidism, constrictive pericarditis, Meig,s syndrome.

Spontaneous bacterial peritonitis:
A third of patients admitted with chronic liver disease and ascites develop spontaneous bacterial peritonitis, which carries a poor prognosis and is diagnosed by a neutrophil count in ascetic fluid of greater than 250 cells/mL. Spontaneous bacterial peritonitis is fatal if left untreated. A diagnostic ascetic tap is essential in all patients admitted with ascites. Early diagnosis, treatment and prevention are critical. Cephalosporin and the quinolone antibiotics are effective.
Hepatic encephalopathy:
The pathogenesis of hepatic encephalopathy is multifactorial:
1. Gut derived substances fail to be cleared because of hepatocellular failure and may be directly shunted to the brain through the portosystemic veins which open up when portal pressure is high( especially in CLD)
2. Impaired protein metabolism leads to build up of neuroactive toxins impairing neurotransmission.
The metabolic changes account for hepatic encephalopathy is supported by its tendency for reversibility. The clinical picture is complex and may include, in approximate order of onset:
Clinical features of Hepatic Encephalopathy:
 Mild confusion
 Mood or behavioural change,especially flattening of affect.
 Asterixis or flapping tremor
 Apraxia, notably constructional apraxia( inability to draw a five-pointed star) and impaired handwriting.
 Dysarthria
 Drowsiness
 Hyperreflexia or hyporeflexia
 Coma and decerebrate posuring
Hepatic encephalopathy may be precipitated by:
• Gastrointestinal bleeding
• Drugs especially sedatives
• Sepsis ( including SBP)
• Other catabolic states., such as surgery or trauma
• Transjugular intrahepatic portosystemic shunt (TIPS)
• Fluid and electrolytes imbalance ( vomiting,diuretic, large volume paracentesis)
• Constipation
• High protein diet

Hepatorenal failure:
HRS is not well understood. It occurs in approximately 18% of cirrhotic patients with ascites,showing splanchnic arterial vasodilatation, decrease effective circulatory volume, ( decrease venous return and cardiac output). Intense renal vasoconstriction, decrease GFR, and normal renal histology. Raised neuropeptide y and activation of the renin-angiotensin-aldosterone axis occur, further worsening renal vasoconstriction. ADH levels also increases in an attempt to restore intravascular volume, it is importantto make the diagnosis only after causes of renal impairment have been excluded.
Tow types of HRS have been described:
HRS 1 is a rapidly progressive deterioration in circulatory and renal function( median survival < 2weeks).
HRS2 is a more steady deterioration ( median survival 6months). Treatment is iv albumin+arterial vasoconstrictor eg.terlipressin to replenish the depleted volume. Haemodialysis ( as supportive therapy) and TIPS may be required. Liver transplantation remain treatment of choice, even after improvement in renal function , snce prognosis is so poor.

Investigations:
Management of cirrhosis depends on aetiology, morphology and hepatic function. It is important to make a diagnosis and exclude potentially reversible causes of further liver deterioration.
1. Liver function tests. These should be used to confirm abnormalities, follow progression and give an idea of prognosis (particularly a low albumin level and prolonged INR). An aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio of >2.0 suggests alcoholic liver disease.
2. Full blood count. This is helpful as anaemia may be caused by chronic disease, blood loss, folate deficiency, bone marrow depression, hypersplenism, haemolysis or sideroplastic anaemia. Roun macrocytes are common in alcoholics. Remember that leucopenia and thrombocytopenia occur in hypersplenism.
3. Renal function tests are important to exclude the hepatorenal syndrome. Hyponatremia is common in cirrhosis.
4. Ascitic tap:
Causes of ascites and interpretation of ascetic fluid studies
Causes:
1. Related to portal hypertension(serum-to-ascites albumin gradient (SAAG) equal to or greater than11 g/l (97% specificity):
a) Cirrhosis
b) Alcoholic hepatitis
c) Cardiac ascites
d) Veno-occlusive disease
e) Budd-Chiari syndrome(hepatic vein thrombosis) or inferior vena caval obstruction
f) Myxoedema
2.Not related to portal hypertension (SAAG<11 g/l):
a) Peritoneal carcinomatosis
b) Peritoneal tuberculosis
c) Pancreatitis
d) Nephritic syndrome
Examination of ascitic fluid following a diagnostic paracentesis:
1. SAAG-equal to or more than 11 g/l in portal hypertension ( e.g.cirrhosis)
2. Blood-suggests malignancy or a recent invasive test
3. Turbid or white fluid- suggest infection or chylous ascites.
4. Cell count: >500cells or >250 polymorphsx106 /l suggest SBP.
5. Lactate-increased in SBP.
6. Amylase-elevated in pancreatic ascites
7. Cytology- for malignant cells
8. Culture-for SBP
5.Ultrasound.This may help eclude biliary obstruction and infiltration. The texure of the liver may suggest infiltration (e.g.fat) or nodularity ( cirrhosis).
6. Liver biopsy. This is adefinitive test and probably should be done if the diagnosis is uncertain, unless there are specific contraindications(e.g.coagulapathy).

7.Finding the cause of chronic liver dysfunction:
The cause Diagnostic test
Chronic viral hepatitis HBsAg,HBeAg, HBV DNA, Anti-HCV antibody, HCV RNA
Genetic haemochromatosis Raised serum iron, transferring saturation and ferritin levels
Increased hepatocytes iron on liver biopsy
Increased hepatic iron index
Autoimmune liver disease Raised IgG levels, positive autoantibodies( antinuclear, antismooth muscle, antiliver and kidney microsomal antigen)
Alcohol-induced liver disease May be raised IgA, relatively higher AST than ALT and disproportionately raised GGT


8.Looking for complications: Abdominal ultrasound and or/CT-scanning and alpha-fetoprotein level to detect hepatocellular carcinoma which develops almost exclusively in cirrhotic livers, and patients with chronic viral hepatitis are most at risk, followed by those with haemochromatosis. HCC is less common in females of reproductive age. Development of HCC can precipitate ascites, encephalopathy and rapid hepatic failure.

Treatment:
Decide whether the patient has acute or acute-on-chronic disease, and decide whether the disease is compensated or decompensated. Management includes treating hepatocellular failure and portal hypertension. Cirrhosis is irreversible. However, removing causative factors,such as alcohol, iron overload and drugs, or treating viral infection is of value.
Hepatic encephalopathy:
 Removing the precipitating factors
 Removing blood from the gut (e.g.enema)
 Giving a low protein diet
 Treating infection
 Correcting electrolytes disturbances
 Avoiding sedative
 Attacking the urea-splitting bacteria with lactulose or lactitol, or neomycin or both
Portal hypertension:
Investigations include endoscopy for eosophageal varices, ascetic tap and abdominal ultrasound with Doppler arterial and venous flow studies.
An attempt should be made to assess the bleeding risk for a patient with varices. High-risk patients(75% risk of haemorrhage over 1 year are those with Child,s class C cirrhosis, gross ascites and large varices.All high-risk patients should be recommended prophylactic treatment-usually with beta-blockers.
Bleeding varices should be managed acutely by replacing blood and correcting coagulation abnormalities. Intravenous octreotide ( or vasopressin combined with glyceryl trinitrate) is first-line therapy but is only a temporary measure.
Oesophageal banding therapy is effective ( and superior to sclerotherapy) in stopping acute bleeding.
Balloon tamponade is now uncommonly required;oesophageal balloon tamponade may worsen the prognosis. To prevent recurrent variceal bleeding, elective endoscopic banding to obliterate varices may be effective.
Beta-blockers (propranolol) can reduce portal pressure and may be useful in patients with good liver function.TIPS is preferable to shunt surgery.
Treatment of ascites cosists of gentle duieresis( maximum weight loss of 500 g per day). Begin with bed rest, salt restriction and spironolactone but increase the dose slowly. Therapeutic paracentesis is a safe alternative inpatients with tense ascites,especially when there is alsoperipheral oedema. Therapeutic paracentesis is contraindicated in renal failure and severe coagulapathy. In resistant ascites, alternatives include TIPS or surgical shunts.
Liver transplantation is the definitive treatment in suitable patients.