Correlation Liver Disfunction and Infection Disease (Dengue and Typhoid Fever) Dr Erwin, SpPD, FINASIM Disampaikan pada acara PIT VI IDI Kota Bogor | 9 Nopember 2013

1. Correlation Liver Disfunction and Infection Disease
(Dengue and Typhoid Fever)
Dr Erwin, SpPD,
FINASIM

2. Functions of the Liver

Metabolic
 Carbohidrat
metabolism
 Protein and lipoprotein metabolism
 Fatty acid metabolism
 Biotransformation of drugs

Storage
 Glycogen
 Vitamins
A, D, E, and K
 Iron and copper

3. 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

4. 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

5. 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

6. Anatomic Patterns of Injury

Inflammation


Degeneration



hydropic
fatty
Necrosis



hepatitis
infarct
Councilman bodies
Fibrosis

cirrhosis

7. 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

8. 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.

9. 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 gammaaminobutyric acid (GABA), endogenous benzodiazepines.
Morphology of brain - oedema; Alzheimer type 2 astrocytic
reaction.

10. FEATURES OF LIVER FAILURE
- hyperbilirubinaemia; deep jaundice = worse prognosis.

- 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).

Jaundice
Haematological

11. FEATURES OF LIVER FAILURE







Infections.
Toxins and drugs.
Viral hepatitis, other infection (dengue and typhoid)
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.

12. FEATURES OF LIVER FAILURE
Liver Injury
Chronic Inflamation
Hepatic Stellete Cells
Portal Hypertension
Activation Kupffer Cell
Cytokines
Liver Cell Damage

13. Acute Liver Failure

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

15. 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.

17. Etiology
Cause
Agent Responsible
Viral Hepatitis
Hep. A, B, D, E, CMV, HSV, seronegative hepatitis
(14-25% in UK)
Drug-related
Dose-related, e.g.paracetamol; idiosyncratic
reactions, e.g. anti-TB, statins, recreational drugs,
anticonvulsants, NSAIDs, many others
Toxins
Vascular events
Other
Carbon tetrachloride, amanita phalloides
Iscahemic hepatitis, veno-occlusive disease, BuddChiari, heatstroke
Pregnancy-related liver disease, Wilson’s
disease, lymphoma, carcinoma, trauma, Dengue, Ty
phoid Fever

19. Epidemiology of Dengue Fever

20. Transmission
Infected
mosquito
Healthy person
Infected
person
Incubation Period: 3 to 14 days
Most commonly 4 to 7 days
20

21. Circulation of Dengue Infected






Hiperbilirubinemia
Hipoalbuminemia
Glukoneogenesis
Hipoglikemia
Asidosis Laktat
Decreased
synthesis of
Clotting factor

22. TYPHOID FEVER

23. Epidemiology
strongly endemic
endemic
sporadic cases

24. Transmission
fecal-oral route
close contact with patients or
carriers
contaminated water and food
flies and cockroaches.

26. liver、spleen、gall、
S.Typhi.
2nd bacteremia
BM ,ect
early stage&acme stage
(1-3W）
stomach
(mononuclear
phagocytes )
Bac. In gall
Bac. In
feces
Lower
ileum
S.Typhi eliminated
convalvescence stage
(4-5w)
peyer's patches &
mesenteric lymph nodes
LN Proliferate,swell
necrosis
defervescence stage
Enterorrhagia,i
ntestinal
perforation
（3-4w）
thoracic
duct
1st bacteremia
(Incubation stage)
10-14d

27. 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

28. Complications
Intestinal hemorrhage
Commonly appear during the second-third week of illness
difference between mild and greater bleeding
often 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.

29. 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.

30. 
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

32. 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

33. Masalah pada pasien ini ?
a.
b.
c.
d.
e.
Febris
Dispepsia
Cephalgia
Diare
Hepatomegali

34. Pemeriksaan Lab
HB :16,7.
HT : 49
L : 4.700
Tr : 98.000
Widal : O 1/320 H 1/160
Analisa pada pasien ini :
a. DHF
b. DF
c. Typhoid
d. A dan C
e. B dan C

35. 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 : 72rb
SGOT/PT 198/114 TUBEK T skala 6
GDS 104 Ur/Cr 40/1,2 Na 133 K 3,4

36. Masalah pada pasien ini
a.
b.
c.
d.
DHF dan Typhoid
Gangguan fungsi hati
DHF, typhoid, inbalance elektrolit
B dan C

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

38. Diskusi




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?