Correlation Liver Disfunction and Infection Disease

(Dengue and Typhoid Fever)

Dr Erwin, SpPD, FINASIM

Metabolic Carbohidrat metabolism Protein and lipoprotein metabolism Fatty acid metabolism Biotransformation of drugs

Storage Glycogen Vitamins A, D, E, and K Iron and copper

Functions of the Liver

Immunological function s Synthesis of immunoglobulins Phagocytosis by Kupffer cells Filtration of bacteria Degradation of endotoxins

Excretion of bilirubin and urea formation

Haematological functions Blood reservoir Haematopoiesis in the foetus

Functions of the Liver

Major Determinants of Disease

The metabolic consequences of liver disease are serious & include toxic accumulations of

metabolic waste (ammonia & bilirubin) drugs & toxins endogenous hormones (estrogen)

Bleeding a deficiency of coagulation factors Edema a deficiency of albumin failure to absorb intestinal fat because of a deficiency of

bile acids Viral hepatitis is a common contagious disease Cirrhosis is the final endpoint for many liver

diseases Portal HTN is the most important consequence of

cirrhosis & can be associated with liver failure & severe hemorrhage

Stones often form in the gallbladder & may pass into & obstruct the bile duct

Response to Injury

Responds well as it has a functional reserve that must suffer a large loss before become symptomatic

Liver function tests (LFTs) enzymes

Lactic dehydrogenase (LDH) Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Alkaline phosphatase (ALKP)

bilirubin albumin PT & PTT viral antigens & antibodies autoimmune antibodies

Anatomic Patterns of Injury

Inflammation hepatitis

Degeneration hydropic fatty

Necrosis infarct Councilman bodies

Fibrosis cirrhosis

Hepatic Failure Die within a few weeks or months May be sudden injury or chronic injury Loss of 90% of function Clinically

jaundice ascites fetor hepaticus hypoalbuminemia hypoglycemia palmar erythema spider angiomata testicular atrophy balding gynecomastia bleeding disorders hepatorenal syndrome hepatic encephalopathy

LIVER FAILURE

Classification. Acute - no pre-existing liver disease.

Chronic - pre-existing liver disease

Causes. Acute - viral hepatitis, drugs, toxins, severe fatty change (eg

fatty liver of pregnancy, Reye syndrome), vascular. Chronic - cirrhosis, chronic hepatitis.

Morphology. Acute - varying degrees of necrosis up to massive liver

necrosis (zonal to panacinar histologically). Chronic - that of cirrhosis or chronic hepatitis.

Chronic liver failure is more common than acute liver failure.

Mortality from liver failure without liver transplantation is 75% to 90%. Drugs and viruses account for about 80% & 15% of cases of acute liver failure respectively; figures vary according to geographical area.

FEATURES OF LIVER FAILURE

Hepatic encephalopathy - a neuropsychiatric disturbance leading to coma. The

cardinal feature of acute liver failure, progressing over hours to days. More insidious in chronic liver failure when it is a sign of worsening liver failure.

- Pathogenesis:- nitrogenous compounds derived from bacterial action in the colon are not metabolised in the failing liver; in addition shunting of portal blood to systemic circulation by-passes the liver.

- Compounds involved - ammonia and derivatives of aromatic amino acids (eg mercaptans, a cause of foetor hepaticus) false neurotransmitters (eg octopamine) neuroinhibitors, eg gamma-aminobutyric acid (GABA), endogenous benzodiazepines. Morphology of brain - oedema; Alzheimer type 2 astrocytic reaction.

Jaundice - hyperbilirubinaemia; deep jaundice = worse prognosis.

Haematological - decreased clotting factors (II,VII,IX,X) results in a bleeding tendency.

Cardiovascular - hyperkinetic circulation. Respiratory - hepatopulmonary syndrome. Renal - hepatorenal syndrome. Endocrine - in chronic failure - gonadal atrophy, gynaecomastia, amenorrhoea. Skin changes - in chronic failure - spider naevi, palmer erythema. Others - impaired metabolism of amino acids, carbohydrates

(hypoglycaemia) and drugs; impaired protein synthesis (low albumin), systemic infections and endotoxaemia. Laboratory investigations

- bilirubin (>300umol/l = poor prognosis). - prothrombin (>50sec.= poor prognosis).

- transaminases. - albumin.

Possible factors precipitating liver failure in chronic liver disease: - increase in liver injury due to virus or alcoholic binge, infection, GIT haemorrhage (which can precipitate encephalopathy, as can excess dietary protein,constipation, drugs, uraemia, hypokalaemia).

FEATURES OF LIVER FAILURE

Infections. Viral hepatitis, other infection (dengue and typhoid) Toxins and drugs. Alcohol.

Therapeutic drugs. Autoimmune. Hepatitis.

Primary biliary cirrhosis. Metabolic. Haemochromatosis.

Wilson disease.Alpha-1-antitrypsin deficiency.

Glycogen storage disease and many others.

Biliary obstruction. Congenital atresia.Sclerosing cholangitis.

Hepatic outflow obstruction. Cryptogenic.

The etiology of cirrhosis varies throughout the world. In the Western world, alcohol is the most common factor at 60% and viral hepatitis 10%. Viral hepatitis is the most common factor in Asia and Africa. Cryptogenic cirrhosis (cause unknown) forms 10%. Once cirrhosis has developed, it is usually not possible to determine the aetiology by morphology alone and results of other investigations are required.

FEATURES OF LIVER FAILURE

FEATURES OF LIVER FAILURE

Liver Injury Chronic Inflamation Activation Kupffer Cell

CytokinesHepatic Stellete Cells

Portal Hypertension Liver Cell Damage

Acute Liver Failure

The mortality rate for acute liver failure ranges between 56% and 80%

Formal diagnosis of acute liver failure

An increase in PT by 4-6 seconds (INR>1.5)

And the development of hepatic encephalopathy (HE).

In a patient without pre-existing cirrhosis and with an illness of less than six months duration.

Cause Agent Responsible

Viral Hepatitis Hep. A, B, D, E, CMV, HSV, seronegative hepatitis (14-25% in UK)

Drug-relatedDose-related, e.g.paracetamol; idiosyncratic reactions, e.g. anti-TB, statins, recreational drugs, anticonvulsants, NSAIDs, many others

Toxins Carbon tetrachloride, amanita phalloides

Vascular events Iscahemic hepatitis, veno-occlusive disease, Budd-Chiari, heatstroke

OtherPregnancy-related liver disease, Wilson’s disease, lymphoma, carcinoma, trauma, Dengue, Typhoid Fever

Etiology

Epidemiology of Dengue Fever

20

Transmission

Infected person

Healthy person

Infected mosquito

Incubation Period: 3 to 14 daysMost commonly 4 to 7 days

Circulation of Dengue Infected

Hiperbilirubinemia

Hipoalbuminemia

Glukoneogenesis

Hipoglikemia Asidosis Laktat Decreased

synthesis of Clotting factor

TYPHOID FEVER

Epidemiology

♦  strongly endemic ♦  endemic

♦  sporadic cases

Transmission

fecal-oral route

close contact with patients or carriers

contaminated water and food

flies and cockroaches.

S.Typhi.

stomach

Lower ileum

peyer's patches &mesenteric lymph nodes

thoracic duct

1st bacteremia(Incubation stage)

10-14d

(mononuclear phagocytes )

2nd bacteremia

liver 、 spleen、 gall、BM ,ect

early stage&acme stage(1-3W）

LN Proliferate,swell necrosis

defervescence stage

（ 3-4w ）

Bac. In gall

Bac. In feces

S.Typhi eliminatedconvalvescence stage

(4-5w)

Enterorrhagia,intestinal perforation

Pathology

essential lesion: proliferation of RES (reticuloendothelial

system ) specific changes in lymphoid tissues and mesenteric lymph nodes.

"typhoid nodules“ Most characteristic lesion: ulceration of mucous in the region of the

Peyer’s patches of the small intestine

Complications

Intestinal hemorrhageCommonly appear during the second-third week of illnessdifference between mild and greater bleedingoften caused by unsuitable food, diarrhea et al

serious bleeding in about 2~8%a sudden drop in temperature 、 rise in pulse 、 and signs of shock followed by dark or fresh blood in the stool.

Intestinal perforation: The more serious .Incidence,1-4% Commonly appear during 2-3 weeks. Take place at the lower end of ileum. Before perforation,abdominal pain or diarrhea,intestinal bleeding . When perforation, abdominal pain, sweating, drop in

temperature, and increase in pulse rate, then, rebound tenderness when press abdomen,

abdomen muscle entasia, reduce or disappear in the sonant extent of liver, leukocytosis .

Temperature rise .peritonitis appear. celiac free air under x-ray.

Toxic hepatitis: common,1-3 weeks hepatomegaly, ALT elevated get better with improvement of

diseases in 2~3 weeks Toxic myocarditis. seen in 2-3 weeks, usually severe toxemia. Bronchitis, bronchopneumonia. seen in early stage

ILUSTRASI KASUS

Pasien Laki-laki 34Thn, Keluhan utama demam 5 hr smrs, disertai sakit

kepala, mual, muntah, nyeri ulu hati, diare dan nyeri sendi.

PF : KU : sakit sedang, CM, TD : 110/70 N 98X/mnt suhu 39O C RR 18X/mnt, lidah

kotor C/P DBN nyeri tekan epigastrium hepar 1 jari BAC limfa tidak teraba

Masalah pada pasien ini ?

a. Febris b. Dispepsiac. Cephalgiad. Diare e. Hepatomegali

Pemeriksaan Lab

HB :16,7. HT : 49 L : 4.700Tr : 98.000Widal : O 1/320 H 1/160

Analisa pada pasien ini : a. DHFb. DFc. Typhoid d. A dan Ce. B dan C

Observasi Selanjutnya

S : Demam mulai berkurang, mual O : TD 100/70 N 96x/mnt suhu 38,2OC

NT ulu hati lab HB :15,9 HT: 48 L :4.900 Tr : 72rbSGOT/PT 198/114 TUBEK T skala 6 GDS 104 Ur/Cr 40/1,2 Na 133 K 3,4

Masalah pada pasien ini

a. DHF dan Typhoidb. Gangguan fungsi hatic. DHF, typhoid, inbalance elektrolitd. B dan C

Planning

RL 40 tts/mnt DPL/hari DL III 1700 kal Pct 3x1 Antasida 3x1 Omeprazole inj 1x1 amp Ceftriaxon 1x2 g Hepatoprotector

D i s k u s i

Apakah infeksi virus bisa bersamaan dengan infeksi bakteri?

Apakah gangguan fungsi hati sering bersamaan dengan penyakit infeksi atau gangguan fungsi hati oleh karena penyebab lain?

Perlukah gangguan fungsi hati pada penyakit infeksi diobati ?

Kapan gangguan fungsi hati menjadi normal pada penyakit infeksi?