Elektrokardiogram (EKG atau ECG)

Elektrokardiogram (EKG atau ECG) adalah grafik yang merekam perubahan potensial listrik jantung yang dihubungkan dengan waktu. Elektrodiografi adalah ilmu yang mempelajari perubahan-perubahan potensial atau perubahan voltage yang terdapat dalam jantung.
Penggunaan EKG dipelopori oleh Einthoven pada tahun 1903 dengan menggunakan Galvanometer. Galvanometer senar ini adalah suatu instrumen yang sangat peka sekali yang dapat mencatat perbedaan kecil dari tegangan (milivolt) pada jantung.
Beberapa tujuan dari penggunaan EKG dapat kegunaan :
1. Untuk mengetahui adanya kelainan-kelainan irama jantung/disritmia
2. Kelainan-kelainan otot jantung
3. Pengaruh/efek obat-obat jantung
4. Ganguan -gangguan elektrolit
5. Perikarditis
6. Memperkirakan adanya pembesaran jantung/hipertropi atrium dan ventrikel
7. Menilai fungsi pacu jantung.

Anatomi dan Fisiologi Jantung

Jantung berukuran sekitar satu kepalan tangan dan terletak di dalam dada, batas kanannya tepat pada sternum kanan dan apeksnya pada ruang intercostalis kelima kiri pada linea mid clavicular. Batas atas jantung terdapat pembuluh darah besar (aorta, truncus pulmonalis, dll); bagian bawah terdapat diafragma; batas belakang terdapat aorta descendens, oesophagus, dan columna vertebralis; sedangkan di setiap sisi jantung adalah paru.

Atrium Kanan
Atrium kanan berada pada bagian kanan jantung dan terletak sebagian besar di belakang sternum. Darah memasuki atrium kanan melalui :

• Vena cava superior pada ujung atasnya
• Vena cava inferior pada ujung bawahnya
• Sinus coronarius (vena kecil yang mengalirkan darah dari jantung sendiri)

Auricula dextra adalah penonjolan runcing kecil dari atrium, terletak pada bagian depan pangkal aorta dan arteria pulmonalis. Pada sisi kiri atrium lubang atrioventrikular kanan membuka ke dalam ventrikel kanan.

Ventrikel Kanan
Ventrikel kanan adalah ruang berdinding tebal yang membentuk sebagian besar sisi depan jantung. Valva atrioventricular dextra (tricuspidalis) mengelilingi lubang atrioventrikular kanan, pada sisi ventrikel. Katup ini, seperti katup jantung lain, terbentuk dari selapis tipis jaringan fibrosa yang ditutupi pada setiap sisinya oleh endocardium. Katup trikuspidalis terdiri dari tiga daun katup. Basis setiap daun katup melekat pada tepi lubang. Tepi bebas setiap daun katup melekat pada chordae tendineae (tali jaringan ikat tipis) pada penonjolan kecil jaringan otot yang keluar dari myocardium dan menonjol ke dalam ventrikel. Lubang pulmonalis ke dalam arteria pulmonalis berada pada ujung atas ventrikel dan dikelilingi oleh valva pulmonalis, terdiri dari tiga daun katup semilunaris.

Atrium Kiri
Atrium kiri adalah ruang berdinding tipis yang terletak pada bagian berlakang jantung. Dua vena pulmonalis memasuki atrium kiri pada tiap sisi, membawa darah dari paru. Atrium membuka ke bawah ke dalam ventrikel kiri melalui lubang atrioventrikular. Auricula sinistra adalah penonjolan runcing kecil dari atrium, terletak pada sisi kiri pangkal aorta.

Ventrikel Kiri
Ventrikel kiri adalah ruang berdinding tebal pada bagian kiri dan belakang jantung. Dindingnya sekitar tiga kali lebih tebal daripada ventrikel kanan. Valva atrioventrikular sinistra (mitralis) mengelilingi lubang atrioventrikular kiri pada bagian samping ventrikel, katup ini memiliki dua daun katup mendapat nama yang sama dengan topi (mitre uskup), tepinya melekat pada chordae tendineae, yang melekat pada penonjolan kerucut myocardium dinding ventrikel. Lubang aorta membuka dari ujung atas ventrikel ke dalam aorta dan dikelilingi oleh ketiga daun katup aorta, sama dengan katup pulmonalis.

Myocardium
Myocardium membentuk bagian terbesar dinding jantung. Myocardium tersusun dari serat – serat otot jantung, yang bersifat lurik dan saling berhubungan satu sama lain oleh cabang – cabang muscular. Serat mulai berkontraksi pada embrio sebelum saraf mencapainya, dan terus berkontraksi secara ritmis bahkan bila tidak memperoleh inervasi.

Endocardium
Endocardium melapisi bagian dalam rongga jantung dan menutupi katup pada kedua sisinya. Terdiri dari selapis sel endotel, di bawahnya terdapat lapisan jaringan ikat, licin dan mengkilat.

Pericardium
Pericardium adalah kantong fibrosa yang menutupi seluruh jantung. Pericardium merupakan kantong berlapis dua, kedua lapisan saling bersentuhan dan saling meluncur satu sama lain dengan bantuan cairan yang mereka sekresikan dan melembabkan permukaannya. Jumlah cairan yang ada normal sekitar 20 ml. Pada dasar jantung (tempat pembuluh darah besar, limfatik, dan saraf memasuki jantung) kedua lapisan terus berlanjut. Terdapat lapisan lemak di antara myocardium dan lapisan pericardium di atasnya.

Arteria Coronaria
Kedua arteria coronaria, kanan dan kiri, menyuplai darah untuk dinding jantung. Arteri ini keluar dari aorta tepat di atas katup aorta dan berjalan ke bawah masing – masing pada permukaan sisi kanan dan kiri jantung, memberikan cabang ke dalam untuk myocardium. Arteri ini menyuplai masing – masing sisi jantung tetapi memiliki variasi individual dan pada beberapa orang, arteria coronaria dextra menyuplai sebagian ventrikel kiri. Arteri ini memiliki relatif sedikit anastomosis antara arteria dextra dan sinistra.

Siklus Jantung
Siklus jantung adalah urutan kejadian dalam satu denyut jantung. Siklus ini terjadi dalam dua fase yaitu :

A. Diastole

Diastole adalah periode istirahat yang mengikuti periode kontraksi. Pada awalnya :

1. Darah vena memasuki atrium kanan melalui vena cava superior dan inferior.
2. Darah yang teroksigenasi melewati atrium kiri melalui vena pulmonalis.
3. Kedua katup atrioventikular (tricuspidalis dan mitralis) tertutup dan darah dicegah untuk memasuki atrium ke dalam ventrikel.
4. Katup pulmonalis dan aorta tertutup, mencegah kembalinnya darah dari arteria pulmonalis ke dalam ventrikel kanan dan dari aorta ke dalam ventrikel kiri.
5. Dengan bertambah banyaknya darah yang memasuki kedua atrium, tekanan di dalamnya meningkat dan ketika tekanan di dalamnya lebih besar dari ventrikel, katup AV terbuka dan darah mulai mengalir dari atrium ke dalam ventrikel.

B. Sistole
Sistole adalah periode kontraksi otot, berlangsung selama 0,3 detik.

1. Dirangsang oleh nodus sino-atrial, dinding atrium berkontraksi, memeras sisa darah dari atrium ke dalam ventrikel.
2. Ventrikel melebar untuk menerima darah dari atrium dan kemudian mulai berkontraksi.
3. Ketika tekanan dalam ventrikel melebihi tekanan dalam atrium, katup AV menutup, chordae tendinea mencegah katup terdorong ke dalam atrium.
4. Ventrikel teruss berkontraksi. Katup pulmonalis dan aorta membuka akibat peningkatan tekanan ini.
5. Darah menyembur keluar dari ventrikel kanan ke dalam arteria pulmonalis dan darah dari ventrikel kiri menyembur ke dalam aorta.
6. Kontraksi otot kemudian berhenti dan dengan dimulainya relaksasi otot, siklus baru dimulai.

Setiap kontraksi diikuti periode refrakter absolut yang singkat saat tidak ada stimulus yang dapat menghasilkan kontraksi, dan diikuti periode refrakter relatif yang singkat saat kontraksi membutuhkan stimulus yang kuat.

Denyut Jantung
Nodus sino-atrial (nodua SA atau pacemaker jantung) adalah daerah kecil serat otot dan sel saraf yang terletak pada dinding jantung di dekat tempat masuk vena cava superior. Pada awalnya sistole, gelombang kontraksi mulai pada nodus ini dan menyebar melalui dinding kedua atrium, merangsang atrium untuk berkontraksi, kontraksi atrium ini tidak menyebar ke ventrikel karena tidak dapat melalui cincin jaringan ikat yang memisahkan atrium dari ventrikel, mencapai dan merangsang nodus atrioventrikularis.

Nodus atrioventrikularis (nodus AV) adalah daerah kecil jaringan khusus di dalam dinding di antara atrium kanan dan ventrikel kanan. Berkas atrioventrikularis (berkas His) adalah pita otot dan serat saraf yang berjalan pada septum di antara kedua ventrikel, mencapai apeks jantung dan di bagi menjadi dua cabang utama, satu untuk tiap ventrikel yang terbagi menjadi beberapa cabang kecil di dalam dinding ventrikel. Gelombang kontraksi menyebar dari nodus AV ke bawah ke berkas AV dan set off kontraksi kedua ventrikel secara simultan. Gelombang kontraksi yang dimulai pada nodus SA menyebabkan atrium berkontraksi tepat sebelum ventrikel karena gelombang segera mencapai atrium dan gelombang yang menuju ventrikel harus melalui berkas AV.

Curah Jantung
Curah jantung bergantung pada :

A. Frekuensi denyut jantung
Saat istirahat biasanya sekitar 70 kali per menit. Frekuensi denyut jantung dikontrol terutama oleh reduksi dalam stimulasi melalui serat nervus parasimpatis (vagus), pengaruh yang lebih kecil oleh stimulasi melalui serat nervus simpatis.

B. Curah sekuncup
Curah sekuncup adalah jumlah darah yang keluar dari ventrikel pada setiap denyut. Saat istirahat biasanya sekitar 70 ml. Pada latihan ringan meningkat sampai 125 ml. Pada awal kontraksi ventrikel, dengan tubuh dalam keadaan istirahat mengandung sekitar 120 ml. Sekitar 50 ml berasal dari ventrikel kiri pada setiap denyutnya.

Curah sekuncup dikontrol oleh perubahan panjang serat otot jantung. Makin panjang (pada otot yang salah) makin besar kontraksinya. Ketika lebih banyak darah memasuki jantung (seperti pada latihan), makin besar kontraksi dan dengan demikian makin besar curah sekuncup.
Curah jantung diukur dengan mengukur jumlah oksigen yang diambil oleh paru per menit, dan berbagai teknik dilusi dengan zat pewarna, isotop radioaktif, dll.

Cirrhosis

Introduction

The term cirrhosis was coined by Laennec in 1826. It is from the Greek word scirrhus to describe the orange or tawny surface of the liver seen at autopsy. There is diffuse fibrosis and the development of widespread nodules. The process can take from weeks to many years to develop. Hepatitis C can take 30 to 40 years to progress to cirrhosis.

Epidemiology

The disease is often silent and may be unsuspected until diagnosed post mortem. 

Worldwide, the largest cause of cirrhosis is hepatitis B with hepatitis C also making a significant contribution. In western societies, alcohol is a major component and in the UK there has been a worrying trend of increasing incidence of injudicious alcohol consumption and alcohol-related disease. According to the report of the Chief Medical Officer for 2001, in 2000 over 4,000 people died from the disease, two thirds of them before their 65th birthday.¹ Large rises in death rates from chronic liver disease and cirrhosis have occurred in most age groups. In 45 to 54 year olds, there has been a greater than 4-fold increase amongst men since the early 1970s and a 3-fold increase in women. In 35 to 44 year olds, there has been an 8-fold increase in men and approaching a 7-fold increase in women. The rise in deaths from cirrhosis amongst younger people is of particular concern and, no doubt, related to binge drinking patterns that appear to be common. In 2000, cirrhosis accounted for nearly 500 deaths in men aged 25 to 44 years and nearly 300 deaths in women of this age group.
Reference to this report is made by the British Liver Trust's Alcohol Related Liver Disease Working Party.²

Between 1960 and 2002, the death rate from cirrhosis in men rose by 69% in England and Wales and 106% in Scotland. Amongst women it rose by nearly half.³ The rising trends in deaths from cirrhosis seen in England are in contrast to our European Union neighbours, although Eastern Europe still has a considerable problem. Most European Union countries are showing declining trends, although generally at levels still higher than the current rates in England. Alcohol consumption increases the rate of progression of cirrhosis from any cause. Within various European countries, there is a good correlation between per capita alcohol consumption and death rate from cirrhosis.⁴ The recent upsurge in binge drinking amongst young women is of particular concern as women are much more susceptible to the adverse effects of alcohol and this is over and above the relative lean body mass. We may expect to see a very significant rise in alcohol related mortality in relatively young women in the near future.

Causes of cirrhosis

There are many causes including:

• Alcohol abuse, either alone or in combination with other factors, especially hepatitis C
• Chronic hepatitis including from hepatitis B and C
• Congestive heart failure or tricuspid regurgitation although this is rarely seen nowadays due to improved management
• Primary biliary cirrhosis
• Secondary biliary cirrhosis occurs from back-pressure due to chronic biliary obstruction and is rarely seen nowadays
• Hereditary haemochromatosis, although it can also be acquired
• Tyrosinaemia
• Wilson's disease
• Alpha-1-antitrypsin deficiency
• Sarcoidosis
• Type IV glycogen storage disease
• Venous outflow obstruction in Budd-Chiari syndrome or veno-occlusive disease
• Drugs including methotrexate and amiodarone
• Certain herbal remedies.⁵

Many of these topics have their own article. A significant number of cases will be classified as cryptogenic cirrhosis. This means of unknown aetiology.

Presentation

Symptoms

Many cases are completely asymptomatic and only discovered on routine blood test. It may present with vague symptoms such as:

• Fatigue
• Malaise
• Anorexia
• Nausea
• Weight loss

In advanced, decompensated liver disease, presentation may include:

• Oedema
• Ascites
• Easy bruising
• Poor concentration and memory

It may present with complications such as bleeding oesophageal varices or spontaneous bacterial peritonitis. 

Take a full drug and alcohol history. Enquire about drugs that have been prescribed, OTC or recreational as well as "alternative remedies" especially herbal.

Signs

Physical signs are also very variable and depend upon the progress of the disease.

• Cutaneous features of cirrhosis include:
  • Jaundice
  • Spider angiomata (spider naevi)
  • Skin telangiectasias (called "paper money skin")
  • Palmar erythema
  • Bruising
  • Petechiae or purpura
  • Hair loss
  • White nails
  • Disappearance of lunulae
  • Finger clubbing, especially in hepatopulmonary syndrome
• General Signs:
  • Tachycardia
  • Raised pulse pressure
  • Orthodeoxia (decrease in PaO₂ with shortness of breath when patient stands up from lying down)
  • Low grade fever
  • Oedema
  • Gynaecomastia
  • Testicular atrophy or amenorrhoea
  • Ascites
  • Collateral vessels around the umbilicus
  • Enlarged spleen
  • Nodular liver
  • Asterixis (flapping tremor) suggests fulminant hepatic failure
  • Increased plantar reflexes

The article on abdominal examination includes description of examination for hepatomegaly andsplenomegaly. To detect asterixis, take the patient's hand and gently hyperextend the wrist and joints of the hand, pushing gently on the tips of the 4 fingers. Ignore the thumb. Hold that position for several seconds and you will feel a slow, clonic flexion, relaxation movement against your hand. This sign tends to suggest quite advanced end stage liver failure and holds a poor prognosis. It has been poetically described as like the patient waving goodbye.

Investigations

This will depend to a considerable extent upon clinical suspicion of the aetiology:

Blood tests

• FBC, U&E, LFTs are fundamental.
• Red cell folate
• Coagulation screen
• Ferritin.
• Viral antibody screen for Hepatitis B and C
• Autoantibody screen for anti-nuclear factor and anti-smooth muscle. Anti-mitochondrial antibodies are a very strong indicator of primary biliary cirrhosis⁶
• Alpha-1-antitrypsin level
• Caeruloplasmin and urinary copper for Wilson's disease
• Check alpha feto-protein as a screen for hepatocellular carcinoma

Interpretation:

• Occult bleeding may produce iron deficiency anaemia or non-anaemic iron deficiency.
• Low ferritin may indicate iron deficiency from diet or blood loss. Ferritin is raised in haemochromatosis.
• Alcohol abuse is often associated with a diet inadequate in folate but even with normal folate there may be macrocytosis.
• Abnormalities of coagulation are a very sensitive test of liver function.
• Hypersplenism may cause thrombocytopenia.
• Poor renal function may represent hepatorenal syndrome.

Imaging

• U/S liver and possibly CT or MRI
• CXR may show an elevated diaphragm and even pleural effusion

Biopsy

Liver biopsy may be helpful but any coagulation defect must be corrected first and blood must be available for transfusion.

Management

The basis of management is to prevent or retard progression and to treat complications as they arise. The former may involve copper chelation in Wilson's disease or venesection in haemochromatosis. Anti-viral agents may be helpful in hepatitis B⁷ or C.⁸ For specific management of specific diseases see the articles about those diseases. Whatever the cause, alcohol must be banned. If diet has been poor this should be rectified and vitamin supplements are often useful. Cholestasis may reduce the absorption of fat soluble vitamins and stores of vitamin K are minimal. Administration by injection may improve clotting factors.

Liver transplantation has become an important strategy in the management of patients with decompensated cirrhosis. Patients should be referred for consideration of liver transplantation after the first signs of hepatic decompensation, with a Child-Pugh score (vide infra) of 7 or more. It may also be performed for hepatocellular carcinoma. Contraindications for liver transplantation include severe cardiovascular or pulmonary disease, active drug or alcohol abuse, malignancy outside the liver, sepsis, HIV or psychosocial problems. Nowadays, survival rates are around 75 to 90% at the end of a year with 70% at 5 years and a good quality of life.⁹ However, transplantation should be performed before complications such as hepato-renal syndrome or massive ascites develop. With the latter, the 1 year survival rate after transplantation is less than 50%. The optimum timing is when the patient is neither too well nor too ill for transplantation.¹⁰

Complications

Portal hypertension

This can lead to oesophageal varices that may bleed profusely. It is a condition with a high mortality. The complex issue has evidence based guidelines, laid down by the British Society of Gastroenterology.¹¹ Beta blockade appears to reduce mortality and they suggest that propranolol is the drug of choice. They also suggest that as infection is a major cause of death after bleeding, that ciprofloxacin at 1g daily should be given for a week.

Ascites

Ascites is a common feature of cirrhosis. The clinical diagnosis of ascites is described in abdominal examination but much smaller volumes may be detected by ultrasound. Its aetiology and management are discussed in ascites and ascites tapping. 

Ascites may be associated with spontaneous bacterial peritonitis that occurs in 15 to 25% of patients in hospital with ascites. It is commonest with low-protein ascites (<1>Escherichia coli, Streptococcus pneumoniae, Klebsiella species, and other gram-negative enteric organisms. It is diagnosed by the presence of neutrocytosis in ascitic fluid, which is defined as greater than 250 polymorphs per cubic millimetre of ascites, with a positive culture. Culture-negative neutrocytic ascites is more common. Both represent serious infections that carry a 20 to 30% mortality rate. There is a 70% chance of recurrence within a year but prophylactic antibiotics can reduce this to 20%. There is much more in the articles about ascites and ascites tapping.

Gross ascites may push on the diaphragm and impair ventilation and it can push out herniae. Pressure on the gut impairs appetite.

Encephalopathy

Hepatic encephalopathy results from the failure of the liver to detoxify certain substances, especially ammonia, although this is not the only toxin involved.¹² It is partly due to toxins from the gut bypassing the liver through anastomotic channels, especially oesophageal varices.

The condition is characterised by mental slowing, somnolence, memory loss, asterixis (hepatic flap) and finally coma. In a late stage the breath may have the characteristic fetor hepaticus.

Treatment includes a low protein diet and laxatives. Encephalopathy may be aggravated or precipitated by shunts or by a GI bleed. The latter is like a sudden high protein meal as blood enters the gut.

A Cochrane review looked at the benzodiazepine receptor antagonist flumazanil¹³ in hepatic encephalopathy. It concluded that flumazenil had a significant beneficial effect on short-term improvement of hepatic encephalopathy in patients with cirrhosis and a highly favourable prognosis but no significant effect on recovery or survival. Flumazenil may be considered for patients with chronic liver disease and hepatic encephalopathy, but cannot be recommended for routine clinical use.

The treatment of hepatic encephalopathy involves the removal of all drugs that require detoxification in the liver and the reduction of protein in the diet. Restricted protein will generally lower the levels of aminoacids and ammonia in the bloodstream and brain. Limitation to 40 grams of protein a day is the usual advice.Lactulose or neomycin are prescribed to lower amino acid production. Non-meat proteins, such as those in vegetables and milk, are preferred. Certain amino acids are used in treatment, since they are considered less likely to cause mental impairment. Zinc supplements may be beneficial. Emphasis should be on preventing the precipitating factors.¹²

The scoring system for hepatic encephalopathy is:

Grade 0 - Subclinical; normal mental status, but minimal changes in memory, concentration, intellectual function, coordination. Grade 1 - Mild confusion, euphoria or depression, decreased attention, slowing of ability to perform mental tasks, irritability, disorder of sleep pattern such as inverted sleep cycle. Grade 2 - Drowsiness, lethargy, gross deficits in ability to perform mental tasks, obvious personality changes, inappropriate behaviour, intermittent disorientation. Grade 3 - Somnolent but rousable, unable to perform mental tasks, disorientation to time and place, marked confusion, amnesia, occasional fits of rage, speech is present but incomprehensible. Grade 4 - Coma, with or without response to painful stimuli.

Hepatorenal syndrome

Hepatorenal syndrome represents a spectrum of renal dysfunction with cirrhosis and is caused by vasoconstriction of large and small renal arteries, so reducing renal perfusion.¹⁴ NSAIDs may potentiate renal vasoconstriction, and reduce glomerular filtration. They must be avoided in patients with decompensated cirrhosis.

Histological changes in the kidneys are minimal and renal function usually recovers well after liver transplantation. A kidney donated by a patient dying from hepatorenal syndrome functions normally when transplanted into a recipient.

Progression of the disease may be rapid (type 1) or slow (type 2). Type 1 often occurs with rapidly progressive liver failure. Haemodialysis gives temporary respite and liver transplantation is required. In type 2, renal insufficiency is stable or slowly progressive but the patient may develop ascites that is resistant to diuretics.

Diagnostic criteria are:

• Creatinine clearance <40>1.5 mg/dL.
• Urine volume <500>
• Urine sodium <10>

Urine osmolality is greater than plasma osmolality. 

Nephrotoxic drugs, including aminoglycosides, should be avoided in patients with cirrhosis. Early hepatorenal syndrome may be treated by aggressive expansion of intravascular volume with albumin and fresh frozen plasma and avoidance of diuretics.

Hepatocellular carcinoma

Cirrhosis is associated with the risk of hepatocellular carcinoma. This risk varies according to cause. It is most often associated with haemochromatosis, alpha-1-antitrypsin deficiency, hepatitis B or C and alcoholic cirrhosis. It is less common in primary biliary cirrhosis and is rare in Wilson's disease. Hepatocellular carcinoma is discussed more fully in its own article.

Prognosis

The Child-Pugh classification system offers important and validated prognosis.

Child-Pugh Classification Criterion Score 1 point Score 2 points Score 3 points Serum albumin (g/L) >3.5 3.0-3.5 <3.0 Serum bilirubin (g/dL) <2.0 2.0-3.0 >3.0 Prothrombin time (seconds) or INR PTT = 1-4 or INR<1.7 PTT = 4-6 or INR = 1.7-2.3 PTT>6 or INR>2.3 Ascites none moderate severe Encephalopathy none mild severe

It is sometimes called the Child-Turcotte-Pugh (CTP) system. Child and Turcotte introduced their scoring system in 1964 as a means of predicting the operative mortality associated with portocaval shunt surgery. Pugh's classification in 1973 substituted albumin for nutritional status. More recent revisions use INR in addition to prothrombin time.

• Score 5-6 class A
• Score 7-9 class B
• Score 10 or more class C

Patients with a score of 10 or more (Class C) have a 1-year survival around 50%. Patients with Class A or B have a 5-years survival rate of 70% to 80%. Ascites, albumin below 3.2 gm/l, and a recent episode of spontaneous bacterial peritonitis are each associated with a one-year survival of 50% or less.

Prevention

• Worldwide the most important factor in prevention of cirrhosis is immunisation against hepatitis B.
• There is no vaccine against hepatitis C but some treatments delay progress and alcohol must be forbidden.
• Hepatitis C is becoming more important as a cause of cirrhosis in western societies.
• Sensible drinking is essential and the CMO's report makes depressing reading.
• Beware of hepatotoxic medications, including herbal remedies.
• Preventive care can significantly reduce the progression of liver disease.
• Weight reduction and exercise can improve liver function in patients with fatty liver.¹⁵

---

Document references

1. CMO report on the Health of the Nation; DOH (2001)
2. Alcohol Related Liver Disease, British Liver Trust
3. Leon DA, McCambridge J; Liver cirrhosis mortality rates in Britain from 1950 to 2002: an analysis of routine data. Lancet. 2006 Jan 7;367(9504):52-6. [abstract]
4. Ramstedt M; Per capita alcohol consumption and liver cirrhosis mortality in 14 European countries. Addiction. 2001 Feb;96 Suppl 1:S19-33. [abstract]
5. Stickel F, Seitz HK, Hahn EG, et al; Z Gastroenterol. 2001 Mar;39(3):225-32, 234-7. [abstract]
6. Jones DE, James OF, Bassendine MF; Primary biliary cirrhosis: clinical and associated autoimmune features and natural history. Clin Liver Dis. 1998 May;2(2):265-82, viii. [abstract]
7. Borgia G, Gentile I; Treating chronic hepatitis B: today and tomorrow. Curr Med Chem. 2006;13(23):2839-55. [abstract]
8. Toniutto P, Fabris C, Pirisi M; Antiviral treatment of hepatitis C. Expert Opin Pharmacother. 2006 Oct;7(15):2025-35. [abstract]
9. O'Grady JG; Acute liver failure. Postgrad Med J. 2005 Mar;81(953):148-54. [abstract]
10. Merion RM; When is a patient too well and when is a patient too sick for a liver transplant? Liver Transpl. 2004 Oct;10(10 Suppl 2):S69-73. [abstract]
11. UK Guidelines on the Management of Variceal Haemorrhage in Cirrhotic Patients, British Society of Gastroenterology (2000); Evidence based guidelines
12. Shawcross D, Jalan R; Dispelling myths in the treatment of hepatic encephalopathy. Lancet. 2005 Jan 29-Feb 4;365(9457):431-3. [abstract]
13. Als-Nielsen B, Gluud LL, Gluud C; Benzodiazepine receptor antagonists for hepatic encephalopathy. Cochrane Database Syst Rev. 2004;(2):CD002798. [abstract]
14. Cardenas A; Hepatorenal syndrome: a dreaded complication of end-stage liver disease. Am J Gastroenterol. 2005 Feb;100(2):460-7. [abstract]
15. Riley TR 3rd, Bhatti AM; Preventive strategies in chronic liver disease: part I. Alcohol, vaccines, toxic medications and supplements, diet and exercise. Am Fam Physician. 2001 Nov 1;64(9):1555-60. [abstract]

---

Internet and further reading

• British Liver Trust; Support and information
• Wolf DC Cirrhosis eMedicine February 2007.

Allergic Phenomena

Allergy is a immune reaction causing local or systemic acute inflammation after repeated exposure to certain antigens (allergens) in susceptible individuals.

Allergies may take many forms, from mild specific food intolerance, hayfever and allergic conjunctivitis to life-threatening anaphylaxis. It is essential to distinguish between allergy and other phenomena. Gastro-intestinal intolerance of NSAIDs, lactose intolerance and simply not liking something are not allergies.

Approximately one-third of people will suffer from an allergy at some time in their life. Around 15% of people are affected by hayfever at some time in their lives, and 1 in 6 children suffer from skin conditions associated with allergy, especially eczema. Asthma is the commonest chronic disease of children, affecting about 11% of children in the UK. Food allergies, particularly to peanuts, are increasing, although they are still relatively uncommon, as is allergy to bee or wasp stings.

Atopy is a condition that is probably caused by immaturity of the T-cell system.¹ It tends to run in families and is associated with atopic eczema, asthma, urticaria and hayfever.

The term allergy was coined by Clemens von Pirquet in 1906.

Prevalence

In one study, around 20% of people thought they suffered from food allergy,² but on formal testing with the gold standard, double blind, placebo controlled food challenge, only 1.4% of adults showed signs. In children the overall prevalence of IgE mediated food allergies is 5 to 7%.³ Allergy to occupational or environmental agents (e.g. house dust mite) is also extremely common and increasing.

Classification

It is important to distinguish between:

• IgE mediated (Coombs type I). Timing is closely related to food intake and specific food triggers may be identified. There may be a personal or family history of atopy. Symptoms are typical and affect more than one organ or system. Non-anaphylactic reactions tend to affect single organ systems eg peri-oral swelling or itching, gastroenterological symptoms (abdominal pain, nausea and D&V), urticaria, rhinitis and bronchospasm, angio-oedema and ultimately anaphylaxis. About a third of patients presenting with anaphylaxis have food allergy.
• Delayed hypersensitivity (type IV) reactions are also immunologically mediated (e.g. the aggravation of eczema by dairy products in susceptible individuals)
• Non allergic food intolerances (e.g. toxins and drugs such as that due to monosodium glutamate causing Chinese Restaurant Syndrome)
• Simple food aversion

Presentation

Allergy can occur at any age. Neonates tend to suffer from atopic dermatitis and food allergies, young children tend to have house dust mite allergy and asthma, teenagers have hay fever while adults may have urticaria, angio-oedema (±aspirin sensitivity), allergy to bee and wasp stings and nasal polyps.³ Symptoms develop 1-10 hours after exposure in 25-50%, becoming more severe and rapid in onset as sensitivity increases.

Certain types of allergy are characteristic in the way they present. Contact dermatitis from cheap jewellery, especially if it contains nickel, is a type IV reaction. Some plants, especially Primula, may produce a delayed reaction. This can be aggravated by sunlight to produce a phyto-photosensitive reaction. Inhaled allergens such as pollens may cause asthma or hayfever. Asthma can also be triggered by chemical irritants rather than allergic sensitivity.

Allergy to medications, especially antibiotics, can be a great problem for the doctor.

• Usually the response is a rash sometimes called a fixed drug reaction but it can be more severe witherythema multiforme with Stevens-Johnson syndrome, exfoliative dermatitis, anaphylaxis and even death.
• Anaphylaxis tends to occur 5 minutes to 2 hours after taking the offending drug.
• Diarrhoea with antibiotics is due to upset of the gut flora and not allergy.
• If antibiotics are used topically there is a much greater risk of allergy. Penicillins are a high risk.Aminoglycosides are less of a problem but still significant.
• Reactions to drugs taken systemically are sometimes typical such as urticaria from aspirin or Stevens-Johnson syndrome from sulphonamides.
• Some reactions that are not allergic must be born in mind including the Jarisch Herxheimer reactionon starting to treat syphilis or the rash that frequently occurs if amoxycillin is given to a patient withglandular fever.
• Only 10% to 20% of patients who reported a history of penicillin allergy were truly allergic when assessed by skin reaction.⁴
• On the other hand, failure to note a reported allergy, giving the drug and producing a severe reaction is medico-legally indefensible.
• Cross reactivity between penicillin allergy and sensitivity to cephalosporins is probably no more than around 10%. The American Academy of Pediatrics, evidence-based guidelines endorse the use of cephalosporin antibiotics for patients with reported allergies to penicillin, for the treatment of acute bacterial sinusitis and acute otitis media.⁵

Gluten sensitivity occurs with allergy to gluten in wheat. It may present, usually in children, with coeliac diseasein which there is subtotal villous atrophy in the small intestine. In adults it may appear as dermatitis herpetiformis in which there is little if any disturbance of the gut but the skin is the affected organ. Both respond to strict gluten avoidance.

History

• Ask about past allergies, personal and family history of asthma, hay fever, dermatitis and childhood eczema.
• Ask about the frequency, duration and severity of the symptoms.
• Do they occur in any particular season, or are there any known triggers?
• Have allergen avoidance and dietary exclusions had any effect?
• Are there any significant environmental factors at home or work?
• Finally take a full drug history, with particular note of any anti-histamine, steroid or adrenaline use.

Investigations

The skin prick test is the most widely used. In primary care, skin prick tests using common aeroallergens (e.g. house dust mite, cat, dog and grass) are safe and can be carried out by a trained nurse. Anaphylactic reactions are extremely rare but it is prudent to have injectable adrenaline readily available.

• The aqueous solutions of allergens are placed on the skin - including just diluent (control) and histamine solution (positive control).
• The skin is then pricked with a new orange needle (25G) for each drop, and excess allergen removed.
• Read after 15 minutes.
• If the wheal is larger than an arbitrary 2mm greater than the negative control, the test is positive.

Remember that any antihistamines the patient is taking will suppress the reaction. 

Although food allergen solutions are available, they are not well standardised, and they are more often associated with anaphylactic reactions. Food tests should not be performed if the diagnosis is very obvious from the history as there is a risk of severe reaction and even fatal anaphylaxis. Dietary challenge in food allergy is time-consuming and requires "wash out" periods. Skin prick tests are a useful procedure for evaluating clinical reactivity to egg, milk, peanut and wheat, but not to soy.⁶

The patch test is available for diagnosing allergic contact dermatitis, using either specific allergens or a "standard set". An eczematous reaction after 48-72 hours indicates a positive result. It can cause contact sensitization and subsequent allergic contact dermatitis, and may need specialist interpretation.

A radioallergosorbent test (RAST) or enzyme linked immunosorbent assay (ELISA) test both measure allergen specific IgE, so are unaffected by drug therapy, safe as they are in vitro, and highly specific. They can be performed when there is extensive skin disease so that patch testing may be difficult, but they are expensive.

Treatment

For emergency treatment see anaphylaxis

With a history of anaphylaxis, absolute allergen avoidance is essential. Advise patients in the use of self-injectable adrenaline (epinephrine) and recommend that they wear Medic Alert bracelets or necklaces.

Anti-histamines, topical steroids (occasionally oral), and allergen avoidance are the mainstays of therapy. Intramuscular steroid injections (eg Kenalog®) are not recommended. They are extremely effective but the risk of adverse effects is not justified. If house dust mite allergy is detected, arrange for mite proof allergen covers for all bedding and ensure the room is well ventilated and vacuumed (obtain appropriate vacuum filter). Remove bedroom carpet if possible, and keep soft toys to a minimum. In the case of pet allergy, the animal should be excluded from the home if possible, although confining the animal to kitchen and outside may be all that can reasonably be expected.

Indications for referral for specialist allergy advice :

• For investigation and management of anaphylaxis
• If diagnosis is uncertain or to exclude allergy in "non-specific" illness
• Food allergy - for specialist dietetic advice
• If occupational allergy is suspected
• Persistent allergic urticaria
• Severe sting allergy or severe hayfever for possible immunotherapy

Allergen injection immunotherapy (hyposensitisation) should only take place in hospital outpatient departments where there is immediate access to resuscitation equipment. It is generally only considered for patients with severe hayfever, inadequately controlled by anti-allergic drugs or in the case of wasp or bee sting anaphylaxis. Patients need at least 60 minutes observation after each injection and longer if even mild hypersensitivity develops. The place of oral cromoglycate for food allergy is disputed. Despite apparent benefit in food intolerance⁷ causing irritable bowel syndrome it has never been a popular treatment.

Of babies allergic to cow's milk about 90% will have grown out of it by age 3 as will 50% of those with allergy to eggs.⁸ Allergy to nuts and cod tends to stay for life.

Allergy and Somatization

One reason for the discrepancy between perceived and true prevalence may be that the self-reporting of allergy is a manifestation of somatization, and that declaring an allergy is more acceptable than "admitting" to psychological problems.⁹ It is known that 65% of those who think they are suffering from the total allergy syndrome fulfil criteria for past or current anxiety or a somatoform disorder, compared with 28% of peers.¹⁰ The label Allergy covers a vast range of human suffering, and a complaint of allergy should prompt explicit questions to uncover (and treat) all the psychological and psychiatric unhappiness with which this label is associated. Patients with gastrointestinal symptoms who report drug or food allergies or worsening of symptoms with various foods are more likely to have functional than organic illness.¹¹ Enquiry about perceived allergies and intolerances may help in the early identification of functional gastrointestinal disorders. Cow's milk allergy can present as constipation in young children.¹²

The withdrawal of a food, especially in young children, should not be undertaken lightly. There is evidence that allergy to cow's milk or bovine proteins may aggravate atopic eczema¹³ but enthusiasm for this is limited.¹⁴Cow's milk can be replaced with goat's milk. If soya milk is used or dairy products simply avoided in young children other sources of calcium must be sought.

In the 1980s there was much enthusiasm for linking hyperactivity in children to artificial colouring in food, especially tartrazine. This seems less fashionable nowadays and the evidence was never strong¹⁵ but it is difficult to distinguish between the effect of removing the colouring and the associated parental attention.

---

Document references

1. Loza MJ, Peters SP, Penn RB; Atopy, asthma, and experimental approaches based on the linear model of T cell maturation. Clin Exp Allergy. 2005 Jan;35(1):8-17. [abstract]
2. Young E, Stoneham MD, Petruckevitch A, et al; A population study of food intolerance. Lancet. 1994 May 7;343(8906):1127-30. [abstract]
3. Bindslev-Jensen C; ABC of allergies: Food allergy; BMJ 1998 316:1299-1302.
4. Salkind AR, Cuddy PG, Foxworth JW; The rational clinical examination. Is this patient allergic to penicillin? An evidence-based analysis of the likelihood of penicillin allergy. JAMA. 2001 May 16;285(19):2498-505. [abstract]
5. Pichichero ME; A review of evidence supporting the American Academy of Pediatrics recommendation for prescribing cephalosporin antibiotics for penicillin-allergic patients. Pediatrics. 2005 Apr;115(4):1048-57. [abstract]
6. Eigenmann PA, Sampson HA; Interpreting skin prick tests in the evaluation of food allergy in children. Pediatr Allergy Immunol. 1998 Nov;9(4):186-91. [abstract]
7. Lunardi C, Bambara LM, Biasi D, et al; Double-blind cross-over trial of oral sodium cromoglycate in patients with irritable bowel syndrome due to food intolerance. Clin Exp Allergy. 1991 Sep;21(5):569-72. [abstract]
8. Rusznak C, Davies RJ; Clinical review ABC of allergies: Diagnosing allergy; BMJ 1998 316:686
9. Howard LM, Wessely S; The psychology of multiple allergy. BMJ. 1993 Sep 25;307(6907):747-8.
10. Black DW, Rathe A, Goldstein RB; Environmental illness. A controlled study of 26 subjects with '20th century disease'. JAMA. 1990 Dec 26;264(24):3166-70. [abstract]
11. Bhat K, Harper A, Gorard DA; Perceived food and drug allergies in functional and organic gastrointestinal disorders. Aliment Pharmacol Ther. 2002 May;16(5):969-73. [abstract]
12. Iacono G, Carroccio A, Cavataio F, et al; Chronic constipation as a symptom of cow milk allergy. J Pediatr. 1995 Jan;126(1):34-9. [abstract]
13. Oranje AP, Wolkerstorfer A, de Waard-van der Spek FB; Natural course of cow's milk allergy in childhood atopic eczema/dermatitis syndrome. Ann Allergy Asthma Immunol. 2002 Dec;89(6 Suppl 1):52-5. [abstract]
14. Werfel T, Breuer K; Role of food allergy in atopic dermatitis. Curr Opin Allergy Clin Immunol. 2004 Oct;4(5):379-85. [abstract]
15. Wender EH; The food additive-free diet in the treatment of behavior disorders: a review. J Dev Behav Pediatr. 1986 Feb;7(1):35-42. [abstract]

---

Internet and further reading

• Cross S, Buck S, Hubbard J; ABC of allergies: Allergy in general practice; BMJ 1998 316:1584-1587.
• Kay AB; Clinical review: ABC of allergies: Good allergy practice; BMJ 1998 316:535-537.
• Atkins D; Food Allergy; emedicine. January 2006