Case Discussion Internal Medicine (3)

Low Gradient SAAG

in patient with MDS

Hariogie Putradi

Moderator: dr. Dian Sukma H, Sp. PK, M. Biomed

1
 Summary of Data Base
Female, 23 y.o

Anamnesa :
 Chief complaint : Patient suffered from black-tarry stools.
 History of present illness :
– Patient came with chief complaint black-tarry stools
appeared since two days ago, it coloured like “petis”, it
happens two until three times a day, around 100 cc. It
appeared until this morning.
– She also complained nausea and vomiting since this
morning, she vomit one time, with maroon-coloured
residue around 10 cc. Patient didn’t complaint about
abdominal pain. 2
 Summary of Data Base

 History of present illness :

• She usually felt weakness all over her body, easily feeling
tired and headache since 7 months ago.
• The complaint got worsened day by day and caused
limitation for her to perform daily activities.
• So she decided to go to Mardi Waluyo Hospital and got
hospitalized there.

3
 Summary of Data Base

 History of present illness :

• Blood laboratory examination showed low level of
Hemoglobin and then the Doctor decided to perform
Bone Marrow examination and the result revealed that
she had hematological problem (MDS) in October 2019.
• She got transfuse 4 bag of PRC back then. After
diagnosed with MDS, she got referred to RSSA.

4
 Summary of Data Base
Past Medical History:
• No remarkable prior medical history
• History of paracentesis 3 times in 7 months. Last
paracentesis 1 day ago.
• No history of taking pain killer drug nor traditional herbs

Family History: -

Social History:
• She is a housewife.
• She was married for 2 years and live with her husband with
no children up to now.
5
 Physical Examination
Tax: 36,9°C
HR = 123
BP = 90/60 RR = 20 Weight: 60 kg
bpm
mmHg tpm Height: 167 cm
regular

GA : looked moderately ill GCS 456

Head/
Anemic +/+, ict - Neck = Within normal limits
Neck
Chest Ictus invisible and palpable at ICS V MCL Sinistra
LHM ~ ictus, RHM ~ SL D
Heart: S1, S2 single, murmur-
Lung:
Symetric, percussion s s Rh - - Wh - - V V
ss -- -- V V
ss -- -- V V6
 Physical Examination

Flat, soefl, Bowel Sound (+) normal,

shifting dullness (+)
Abdomen: Liver/ unpalpable, liver span 10 cm,
epigastrium tenderness (-)
Lien/ Traube space dullness(+)

Extremities: edema -/-, warm acral

Genitalia ext: RT/ Tonus sphincter ani (+); colon mucous
slippery; melena (+); hematoschezia (-)

7
LABORATORY RESULT
05/02/ 07/02/ Normal
HEMATOLOGY - -
20 20 reference
Hemoglobin 9,70 - 6,00 - 11,4 – 15,1 g/dL
Erythrocyte 4,01 - 2,45 - 4,0 – 5,0.106 /µL
Leukocyte 6,07 - 7,38 - 4,7 - 11,3 .103 /µL
Hematocrit 31,70 - 19,80 - 38 – 42 %
Thrombocyte 197 - 179 - 142 – 424. 103 /µL
MCV 79,10 - 80,80 - 80 – 93 fL
MCH 28,50 - 29,00 - 27 – 31 pg
MCHC 30,60 - 30,30 - 32 – 36 g/dL
RDW 17,30 - 18,00 - 11,5-14,5
Diff.count: 1/0/0/ 0/0/0/ 0-4/<1/3-5/
Eo/Baso/Neut/ - -
Lymph/Mono 77/18/4 74/21/5 51-67/25-33/2-5

8
 LABORATORY RESULT
Clinical 05/02/ 06/02/ Normal
Chemistry - - reference
20 20
16,6 – 48,5
Ureum 9,9 - - - mg/dL
Creatinine 0,50 - - - <1,2 mg/dL
eGFR 136,419 - mL/min/1,73m2
(CKD EPI) - -
AST/SGOT - 38 - - 0 – 32 U/L

ALT/SGPT - Para- 28 - - 0 – 33 U/L

centesis
Albumin 2,52 1,24 - - 3,5 – 5,5 g/dL
Total Bilirubin - 0,99 - - <1,0 mg/dL

Direct 0,60 <0,25 mg/dL

Bilirubin - - -
Indirect 0,39 <0,75 mg/dL
Bilirubin - - - 9
 LABORATORY RESULT
Clinical 05/02/ 06/02/ - - Normal
Chemistry reference
20 20
SI - 42 - - 49-151 ug/dL
TIBC - 109 - - 250-350
ug/dL
Transferin - 39 - - 16-45 %
saturation

05/02/ - - - Normal
Electrolyte reference
20
136 - 145
Natrium 144 - - -
mmol/L
3,5 - 5,0
Kalium 2,21 - - -
mmol/L
98 - 106
Chloride 124 - - -
mmol/L
10
 LABORATORY RESULT

Hemostasis
PPT 06/02/20 Normal reference
Patient 16,50 second 9,4 – 11,3
Control 11,2 second -
INR 1,64 < 1,5
APTT
Patient 31,00 second 24,6 – 30,6
Control 25,5 second -

11
 LABORATORY RESULT
ASCITES FLUID ANALYSIS
06/02/20 Normal reference
Macroscopic
Color Yellow
Clot Negative
Clarity Rather cloudy
Microscopic
Erythrocyte 1900/µL
Leukocyte 110/µL
PMN 45%
MN 55%
12
 LABORATORY RESULT
ASCITES FLUID ANALYSIS
Clinical Chemistry 06/02/ Normal reference
20
Total Protein 0,81 <3 g/dL
Glucose 130 >60 mg/dL
Chylous > 110 mg/dL
Triglyceride 24 Pseudochylous <50 mg/dL
Transudate (<45-60 mg/dL)
Cholesterol 11 Exudate (>45-60 mg/dL)
Transudate (<320 IU/L)
LDH 61 Exudate (>320 IU/L)
Ascites Albumin 0,43 g/dL
Serum Ascites Albumin
Gradient (SAAG)
0,81 g/dL
SAAG < 1.1
Low Gradient
13
 Urinalysis 05/02/20 Reference
Clarity Clear
Colour Yellow
pH 6,0 4.5 - 8.0
SG 1.025 1.005 - 1.030
Glucose Negative Negative
Protein Trace Negative
Keton Trace Negative
Bilirubin 2+ Negative
Urobilinogen 33 <17 umol/L
Nitrit Positive Negative

14
 Urinalysis 05/02/20 Reference
Leukocyte Trace Negative
Blood Negative Negative
Epithel 3,3 ≤ 3 /LPF
Cast Negative
Erythrocyte 0,9 ≤ 3 /HPF
Eumorphic: - %
Dismorphic: - %
Leukocyte 8,2 ≤ 5 /HPF
Crystal - HPF
Bacteria 397,3 x 103 /mL ≤ 93 x 103 /mL

15
16
Peripheral Blood Smear (22/10/2019)
RSUD Mardi Waluyo Blitar
Hb 9,47 g/dL
Leukocyte 4.090 / cmm
Thrombocyte 76.600 / cmm
PCV 30,1 %
LED 48 mm/hour
Reticulocyte 34 promil
Diff count 1/1/5/65/20/8
Erythrocyte Normochromic normocyter
Leukocyte normal count, blast cell (-)
Thrombocyte decreased count, and normal
morphology

17
 Bone Marrow Aspiration (22/10/2019)
RSUD Mardi Waluyo Blitar

1. Cellularity: Hypercelullar
2. M:E = 1:1
3. Erythropoiesis: increased activity, dyserythropoiesis
(binucleated, internuclear bridging, giant cell)
4. Granulopoiesis: normal activity, dysgranulopoiesis
(pseudo pelger-huet, giant stab)
5. Thrombopoiesis: normal activity, dysmegakaryopoiesis
(hyponucleated megakaryocyte)
6. Fe storage : negative
Conclusion: Myelodysplasia Syndrome (MDS)
 Chest X-Ray (26/12/2019)

Conclusion: normal chest x-ray

 Abdominal USG (02/02/2020)

Conclusion:
 Chronic Liver Disease impressed Cirrhosis hepatis with Severe fibrosis
(Nishiura Score = 7) suspected portal hypertension
 Splenomegaly
 Ascites permagna
 Left pleural effusion
 Therapy

 IVFD NS 1500 cc/24 hours

 Inj. Omeprazole 2x40 mg
 Inj. Metoclopramide 3x10 mg
 po: Lactulose syr 3xCI
 Data Interpretation
• Laboratory finding showed:
 Normochromic anisocytosis anemia,
hypoalbuminemia, low SI & TIBC, hypokalemia, low
gradient SAAG, UL: bilirubinuria, urobilinogenuria,
positive nitrite, leukocyturia, bacteriuria, BMA:
Myelodysplasia Syndrome (MDS), Abdominal USG:
Chronic Liver Disease impressed Cirrhosis hepatis,
Splenomegaly, Ascites permagna, Left pleural effusion.

22
 Data Interpretation
• Based on medical history, physical examination,
laboratory data & other examinations showed:
Myelodysplasia Syndrome (MDS); Liver Cirrhosis
with complication susp. esophageal varices, portal
hypertension gastropathy, and anemia; Susp. UTI.

• Suggestions: RBG, ALP, GGT, SPE, HBsAg, Anti

HCV, BGA, urine culture, urine electrolyte, endoscopy.
• Monitoring: CBC, PBS, SI, TIBC, serum electrolyte,
SAAG (re-examine), urinalysis.

23
 Discussion
Establishment of Diagnosis

Low Gradient SAAG

Hypokalemia

22
 25

Establishment of Diagnosis
Myelodysplasia Syndrome (MDS)
• MDS  are a group of clonal BM neoplasms
characterized by ineffective hematopoiesis, manifested
by morphologic dysplasia in hematopoietic cells and
by peripheral cytopenia(s).
• Epidemiology
– there are approximately 10,000 cases diagnosed
annually in the United States
– MDS occurs most commonly in older adults, with a
median age at diagnosis in most series of ≥65 years
and a male predominance .
BLOOD, 19 MAY 2016xVOLUME 127, NUMBER 20
 26

Myelodysplasia Syndrome (MDS)

• MDS  has been associated with environmental
factors (eg, exposure to chemicals, particularly
benzene, radiation, tobacco, or chemotherapy drugs),
inherited genetic abnormalities (eg, trisomy 21,
Fanconi anemia, Bloom syndrome, ataxia
telangiectasia), and other benign hematologic
diseases (eg, paroxysmal nocturnal hemoglobinuria,
congenital neutropenia).
• Familial MDS, while rare, has been associated with
germ line mutations in RUNX1, ANKRD26, CEBPA,
DDX41, ETV6, TERC, TERT, SRP72, and GATA2.

BLOOD, 19 MAY 2016xVOLUME 127, NUMBER 20

Patophysiology MDS

27
 28

Myelodysplasia Syndrome (MDS)

The 2016 WHO classification of MDS
• MDS with single-lineage dysplasia (MDS-SLD) – 1 or 2 blood
cytopenias; in bone marrow, dysplasia in ≥ 10% of one cell line,
< 5% blasts
• MDS with multilineage dysplasia (MDS-MLD) – 1-3 blood
cytopenias, < 1 × 109/L monocytes; in bone marrow, dysplasia in
≥ 10% of cells in ≥ 2 hematopoietic lineages < 15% ring
sideroblasts (or < 5% ring sideroblasts if SF3B1 mutation
present) < 5% blasts
• MDS with ring sideroblasts (MDS-RS) – Anemia, no blasts; in
bone marrow, ≥ 15% of erythroid precursors with ring
sideroblasts or ≥ 5% ring sideroblasts if SF3B1 mutation is
present
 29

Myelodysplasia Syndrome (MDS)

The 2016 WHO classification of MDS
• MDS with isolated del(5q) – Anemia, platelets normal or
decreased; in bone marrow, unilineage erythroid dysplasia,
isolated del(5q), < 5% blasts ± one other abnormality
except -7/del(7q)
• MDS with excess blasts (MDS-EB) – 1-3 blood cytopenias,
0-3 dysplastic bone marrow lineages, and 5-9% blasts in
bone marrow or 2-4% blasts in blood (MDS-EB1) or 10-19%
blasts in bone marrow or 5-19% blasts in blood (MDS-EB2)
• Unclassifiable MDS – Cytopenias, ±1% blasts on at least 2
occcasions; in bone marrow, single-lineage dysplasia or no
dysplasia but characteristic MDS cytogenetics, < 5% blasts
 30

Myelodysplasia Syndrome (MDS)

The 2016 WHO classification of MDS
• The WHO classification also includes provisional category of
refractory cytopenia of childhood, with cytopenias and < 2%
blasts in peripheral blood and, in bone marrow, dysplasia in 1–3
lineages and < 5% blasts.
Signs and symptoms
• are nonspecific.
• many patients are asymptomatic at diagnosis and only come to
the physician's attention based upon abnormalities found on
routine blood counts (eg, anemia, neutropenia, and
thrombocytopenia).
• Others present with symptoms or complications resulting from
a previously unrecognized cytopenia (eg, infection, fatigue).
This Patient
 Female, 23 yo Myelo-
 Lab: Normochromic anisocytosis anemia, dysplasia
 BMA: Hypercelullar, M:E = 1:1, Syndrome
dyserythropoiesis (binucleated, internuclear (MDS)
bridging, giant cell), dysgranulopoiesis
(pseudo pelger-huet, giant stab),
dysmegakaryopoiesis (hyponucleated
megakaryocyte), Fe storage : negative
Myelodysplasia Syndrome (MDS),

Monitoring: CBC, PBS, SI, TIBC

28
 32

Liver Cirrhosis

• Liver Cirrhosis (LC)  diffuse hepatic process

characterized by fibrosis and conversion of the
normal liver architecture into structurally abnormal
nodules.
• Clinically it classified as compensated and
decompensated. Decompensated LC includes
cases with ascites, variceal bleeding, hepatic
encephalopathy, or jaundice. 
• Alcohol abuse and viral hepatitis are the most
common causes of cirrhosis

Tae Suk et al. 2012. Revision and Update clinical practice guidelines for liver cirrhosis. Korean Journal Hepatology
 Pathogenesis Liver Cirrhosis

Macrophages  initiate the recruitment and

transformation of resident quiescent hepatic stellate cells
(HSCs) to a myofibroblast (highly activated, proliferative,
motile, and contractile)  redundant extracellular matrix
(ECM)  accumulated  Liver Cirrhosis induction.
33
RSC Adv., 2018, 8, 6699–6708
 Child-Pugh-Turcotte (CPT)

0,99
2,52

1,64
Keith D. Lindor, MD
BMJ Best Parctice
Cirrhosis
BMJ Publishing Group Ltd
2018. Score: 9
23 25
 Complications of Cirrhosis
• Portal hypertension • Coagulopathy
• Gastroesophageal varices • Factor deficiency
• Portal hypertensive • Fibrinolysis
gastropathy • Thrombocytopenia
• Splenomegaly, hypersplenism • Bone disease
• Ascites • Osteopenia,
• Spontaneous bacterial osteoporosis,
peritonitis osteomalacia
• Hepatorenal syndrome • Hematologic
• Hepatic encephalopathy abnormalities
• Hepatopulmonary syndrome • Anemia
• Portopulmonary hypertension • Hemolysis
• Malnutrition • Thrombocytopenia
• Neutropenia

26
Harrisons Principles of Internal Medicine, 18e
 36
Yasuko Iwakiri, Clinics in liver disease, 2014
PORTAL HYPERTENSION & ANEMIA

Acute gastrointestinal hemorrhage :

• common and potentially serious
complication of portal hypertension.
• usually caused by rupture of an
esophageal varices (70%).
• the second most common cause of mortality
in patients with cirrhosis.

World J Gastroenterol 2009 October 7; 15(37): 4653-4658 37

PORTAL HYPERTENSION & ANEMIA

• According to Sheila Sherlock and Oxford text

book of hepatology  most common anemia
seen in cirrhotic patients is normochromic and
normocytic anemia.
• Incidence of normochromic and normocytic
anemia according to :
• study by Malhotra (1951) was 90%.
• study by Bhatia (1961)  was 59%.
• study by Mishra et al (1982)  was 79%.

J of Evidence Based Med & Hlthcare, p2349-2570/

38
Vol. 2/Issue 7/Feb 16, 2015
Liver Cirrhosis In This Patient
Female, 23 y.o Liver Cirrhosis
Laboratory result with complication
• Normochromic anisocytosis
susp. esophageal
anemia, hypoalbuminemia, low
SI & TIBC, low gradient SAAG,
varices, portal
Abdominal USG: Chronic Liver hypertension
Disease impressed Cirrhosis gastropathy, and
hepatis, Splenomegaly, Ascites anemia.
permagna, Left pleural effusion

Suggestions: RBG, ALP, GGT, SPE, HBsAg, Anti

HCV, endoscopy.
Monitoring: CBC, PBS, SI,TIBC, SAAG(re-examine),
urinalysis. 27
 Urinary Tractus Infection (UTI)

• Urinary tract infection (UTI)  is a term that

encompasses a broad range of clinical entities that
have in common a positive urine culture.
• A conventional threshold  is growth of >100,000
colony-forming units per milliliter from a midstream-
catch urine sample.
• In symptomatic patients, a smaller number of
bacteria (between 100 and 10,000 colony-forming
units per milliliter of midstream urine) is recognized
as an infection.

40
Ferri's Clinical Advisor, E-book, 2018
 Urinary Tractus Infection (UTI)
LABORATORY TESTS
• Urinalysis with microscopic evaluation of clean-catch
urine for bacteria and pyuria. The presence of ≥10
leukocytes/μl of unspun urine from a midstream catch
indicates UTI. If urine dipsticks are used, the presence
of positive nitrite and positive leukocyte esterase is
indicative of UTI in a symptomatic patient.
• Urine culture and sensitivity are useful in complicated
UTIs.
• Complete blood count with differential count (shows
leukocytosis).
41
Ferri's Clinical Advisor, E-book, 2018
This Patient
Female, 23 yo

UL: positive nitrite, leukocyturia, bacteriuria,

Susp. UTI

Suggestions: BGA, urine culture.

Monitoring: urinalysis.

28
 Low Gradient SAAG
• The term ‘ascites’ denotes the pathologic
accumulation of fluid in the peritoneal cavity.
• The most common cause of ascites is portal
hypertension secondary to chronic liver
disease, which accounts for more than 80%
cases.
• The most common causes of non-portal
hypertensive ascites include infections and
intra-abdominal malignancy.
ROLE OF SERUM-ASCITES ALBUMIN GRADIENT IN DIFFERENTIAL
DIAGNOSIS OF ASCITES
M. Younas, Abdus Sattar, Rizwan Hashim, Aamir Ijaz, M. Dilawar,
Sayed Mohsin Manzoor, Asif Ali, Farooq Ahmad Khan
J Ayub Med Coll Abbottabad 2012;24(3) 43
 SAAG
• The SAAG is the best single test for classifying ascites
into portal hypertensive (SAAG > 1.1 g/dL) and non–
portal hypertensive (SAAG < 1.1 g/dL) causes.
• Calculated by subtracting the ascitic fluid albumin
value from the serum albumin value, it correlates
directly with portal pressure.
• The accuracy of the SAAG results is approximately
97% in classifying ascites.
• The terms high-albumin gradient and low-albumin
gradient should replace the terms transudative and
exudative in the description of ascites.
30
 Old New
due to portal hypertension
Transudate High gradient
(< 2,5 g/dL) (≥1,1 g/dL) Parameter:
Parameter: SAAG
AFTP (Serum
(Ascites Ascites
Fluid Total Albumin
Protein) Exudate Low gradient Gradient)
(≥ 2,5 g/dL) (<1,1 g/dL )
ROLE OF SERUM-ASCITES ALBUMIN GRADIENT IN DIFFERENTIAL
DIAGNOSIS OF ASCITES
unrelated to portal hypertension
M. Younas, Abdus Sattar, Rizwan Hashim, Aamir Ijaz, M. Dilawar,
Sayed Mohsin Manzoor, Asif Ali, Farooq Ahmad Khan 31
J Ayub Med Coll Abbottabad 2012;24(3)
 This patient…
Test Result Test Result Reference ranges
Macroscopic Chemistry
Color Yellow Total 0,81 g/dL <3
protein AFTP < 2,5
Clot Negative Glucose 130 >60 g/dL
mg/dL Transudate
Clarity Rather Triglyceride 24 mg/dL Chylous: >110
cloudy Pseudochylous: <50
Microscopic 1.900/ Cholesterol 11 mg/dL Transudate: <45-60
RBC µL Exudate: >45-60
WBC 110/µL LDH 61 IU/L Transudate: <320
Exudate: >320 Transudate
PMN 45% -
- -
MN 55% - - -

Serum albumin: 1,24 g/dL Low

Ascites albumin: 0,43 g/dL Gradient
SAAG: 0,81 32
 Low Gradient SAAG
• A SAAG less than 1.1 g/dL  suggests the cause of
ascites is not related to portal hypertension.
• Low SAAG ascites (<1.1 g/dL)  is usually caused by
peritoneal malignancies, chronic peritoneal
infection (i.e., mycobacterium tuberculosis), and
nephrotic syndrome.
• Cancers that spread to the omentum and result in
ascites are typically of ovarian, gastric, or pancreatic
origin. It is uncommon for hepatocellular carcinoma
to cause malignant ascites.

30
CLINICAL LIVER DISEASE, VOL 7, NO 3, MARCH 2016
 Low Gradient SAAG
• However, the presence of low SAAG in the clinical
context of suspected cirrhosis  should be repeated
because up to 3.3% of patients with portal
hypertension may have SAAG less than 1.1 g/dL.
• A repeat paracentesis  will often reveal a high
SAAG.

30
CLINICAL LIVER DISEASE, VOL 7, NO 3, MARCH 2016
 Hypokalemia
• It is usually defined as a serum potassium of less than
3.5 mmol/L
• Patients with mild hypokalemia (serum potassium 3,0-
3,5 mmol/L) usually have no symptoms
• More severe hypokalemia (serum potassum of less
than 2,5 mmol/L0, generalised weakness can occur,
develop muscle necrosis (rhabdomyolisis) and
paralysis.
• Both mild and severe hypokalemia can increase the
incidence of cardiac arrhytmias.
Rastergar A, Soleimani M. Hypokalaemia and hyperkalaemia. Postgraduate 49
Medical Journal. 2001 Dec 1;77(914):759-64.
50
 Hypokalemia in cirrhosis

• Hypokalemia  is a serious complication of

cirrhosis, its treatment or due to its complications.
• 50-80% of patients with treatment for cirrhosis and
its complications develop hypokalemia.
• Hypokalemia  results due to the movement of
potassium from intracellular to extracellular stores.

30
IAJPS 2018, 05 (03), 1831-1838
 Hypokalemia in cirrhosis

• Several factors including diet, gastrointestinal

losses, and diuretic treatment  may affect
adversely the potassium status of cirrhotic
patients.
• Use of diuretics  can result in hypokalemia in
subjects with chronic liver disease and ascites.
• Large volume paracentesis  also contribute for
hypokalemia.

30
IAJPS 2018, 05 (03), 1831-1838
In This Patient
Female, 23 yo
Lab: hypokalemia
Ax : nausea and vomiting since this morning, she vomit
one time, with maroon-coloured residue around 10 cc,
history of paracentesis 3 times in 7 months. Last
paracentesis 1 day ago.

Hypokalemia d.t. GI Loss dd. Paracentesis

Suggestions: urine electrolyte.

Monitoring: serum electrolyte.
28
 Conclusion
• It has been discussed female 23 y.o with
Myelodysplasia Syndrome (MDS); Liver Cirrhosis
with complication susp. esophageal varices, portal
hypertension gastropathy, and anemia; Susp. UTI.

• Low SAAG in liver cirrhosis  should be repeated

because up to 3.3% of patients with portal
hypertension may have SAAG less than 1.1 g/dL 
will often reveal a high SAAG.

• Hypokalemia in this patient  d.t. GI Loss dd.

Paracentesis
54
 Conclusion
• Suggestions: RBG, ALP, GGT, SPE, HBsAg,
Anti HCV, BGA, urine culture, urine electrolyte,
endoscopy.

• Monitoring: CBC, PBS, SI, TIBC, serum

electrolyte, SAAG (re-examine), urinalysis.

55
THANK YOU

56
No PCCL PL IDx PDx
1 Female, 23 yo Myelo- Myelo- Monitoring:
dysplasia dysplasia CBC, PBS, SI,
 Lab: Normochromic
Syndrome Syndrome TIBC
anisocytosis anemia,
(MDS) (MDS)
 BMA: Hypercelullar, M:E
= 1:1, dyserythropoiesis
(binucleated,
internuclear bridging,
giant cell),
dysgranulopoiesis
(pseudo pelger-huet,
giant stab),
dysmegakaryopoiesis
(hyponucleated
megakaryocyte), Fe
storage : negative
Myelodysplasia
Syndrome (MDS)

57
No PCCL PL IDx PDx
2 Female, 23 yo Liver Liver Cirrhosis Suggestions:
Cirrhosis with RBG, ALP,
complication GGT, SPE,
Laboratory result susp. HBsAg, Anti
Normochromic esophageal HCV,
anisocytosis anemia, varices, portal endoscopy.
hypoalbuminemia, low hypertension
SI & TIBC, low gradient gastropathy, Monitoring:
SAAG, Abdominal and anemia. CBC, PBS,
USG: Chronic Liver albumin, SI,
Disease impressed TIBC, SAAG
Cirrhosis hepatis, (re-examine),
Splenomegaly, Ascites urinalysis.
permagna, Left pleural
effusion

58
No PCCL PL IDx PDx
3 Female, 23 yo Hypo- Hypo- Suggestions:
kalemia kalemia urine
d.t. GI d.t. GI electrolyte.
Lab: hypokalemia Loss dd. Loss dd.
Paracente Paracente
Monitoring:
Ax : nausea and sis sis
serum
vomiting since this electrolyte.
morning, she vomit
one time, with
maroon-coloured
residue around 10
cc, history of
paracentesis 3 times
in 7 months. Last
paracentesis 1 day
ago.

59
 Myelodysplasia-Like Syndrome and
End-Stage Liver Disease Report of 2 Cases
Yi-Kong Keunga David Morganc David Hodgesb Melissa Blannc
Everardo Cobosa

• Mild-to-moderate pancytopenia is commonly associated

with liver cirrhosis.
• It is usually attributed to hypersplenism due to portal
hypertension and liver cirrhosis.
• We report 2 cases of myelodysplastic-like syndrome
associated with liver cirrhosis caused by primary biliary
cirrhosis and ·1-antitrypsin deficiency.
• The etiology of myelodysplasia and its implication in liver
transplantation is discussed.
60
Acta Haematol 2001;105:100–102
 Myelodysplasia-Like Syndrome and
End-Stage Liver Disease Report of 2 Cases
Yi-Kong Keunga David Morganc David Hodgesb Melissa Blannc
Everardo Cobosa

• Since liver cirrhosis is not listed as one of the known causes of

myelodysplasia, it is conceivable that the myelodysplasia-like
morphology and the end-stage liver disease are isolated
events and the concurrent diagnoses in these cases are simply
coincidental.
• Alternatively, it is possible that the myelodysplasia-like
morphology manifests in end-stage liver disease presumably
as a result of accumulation of toxic metabolites that affect the
normal maturation of the bone marrow progenitors.
61
Acta Haematol 2001;105:100–102
 Myelodysplasia-Like Syndrome and
End-Stage Liver Disease Report of 2 Cases
Yi-Kong Keunga David Morganc David Hodgesb Melissa Blannc
Everardo Cobosa

• The distinction in these two scenarios is important in

the era of liver transplantation.
• If the myelodysplasia is an independent event, these
patients would unlikely be transplanted because of
the presence of serious concomitant medical problems.
• However, if the myelodysplasia is a result of end-stage
liver disease, liver transplantation may theoretically
be able to reverse the myelodysplastic process.
62
Acta Haematol 2001;105:100–102
 Myelodysplasia-Like Syndrome and
End-Stage Liver Disease Report of 2 Cases
Yi-Kong Keunga David Morganc David Hodgesb Melissa Blannc
Everardo Cobosa

• These diseases have not previously been associated

with myelodysplastic syndrome.
• Neither of the patients was exposed to any toxic
chemicals or drugs that could cause myelodysplastic
syndrome.

63
Acta Haematol 2001;105:100–102
 prognostic scoring systems for MDS
• International Prognostic Scoring System (IPSS)

64
 prognostic scoring systems for MDS
• The Revised International Prognostic Scoring System (IPSS-R)

65
 prognostic scoring systems for MDS
• The WHO Prognostic Scoring System (WPSS)

66
 prognostic scoring systems for MDS
• Risk Groups

• Lower-risk MDS tends to grow and progress slowly. It may not cause many or
even severe symptoms for a long time. Hence, less intensive treatment is
frequently used.

• In contrast, higher-risk MDS is likely to progress more quickly or become AML

more quickly without treatment. It may cause more symptoms and health
complications in a short amount of time. Thus, more intensive treatment is often
67
required.
 Criteria Remission MDS
• 4. Clinical benefit associated with a response duration of 8 weeks
versus 4 weeks

• In higher-risk MDS, a CR or PR lasting for 4 weeks or more may be

associated with improved survival based on experience with AML
and MDS.42  The need for an additional marrow confirmatory
specimen a month later is often impractical and has not been
required in recent guidelines.

• In lower-risk MDS, durability of a response (mostly HI) should be

sustained for 8 weeks or more to prove clinically beneficial.
Stability of the improved counts would be sufficient to define CR
or PR without a need to repeat a second bone marrow study.

Clinical application and proposal for modification of the International Working Group (IWG) response criteria in 68
myelodysplasia . Blood (2006) 108 (2): 419–425.
 Criteria Remission MDS

Clinical application and proposal for modification of the International Working Group 69
(IWG) response criteria in myelodysplasia . Blood (2006) 108 (2): 419–425.
Criteria Remission MDS

70
Criteria Remission MDS

71
Criteria Remission MDS

72
 Hypokalemia and hepatic encephalopathy in
cirrhosis

• The effect of hypokalemia is thought to be mediated by

potassium movement out of the cells to replenish
extracellular stores.
• Electroneutrality is maintained in part by movement of
extracellular hydrogen into the cells, the intracellular
acidosis in renal tubular cells increased the production of
ammonia.
• The often concurrent metabolic alkalosis may contribute
by promoting the conversion of ammonium (NH4+), a
charged particle which cannot cross the blood brain
barrier into ammonia, which can enter the brain. 73
 Hypokalemia in cirrhosis
• Hypokalemia results due to the movement of potassium
from intracellular to extracellular stores.
• Extracellular hydrogen moves into the cells to maintain
Electroneutrality, thus ammonia production increases due
to intra cellular acidosis in renal tubular cell.
• The conversion of ammonium (NH4+) is promoted by
concomitant contribution of metabolic alkalosis; NH4+ is a
charged element that cannot cross the blood brain barrier,
while ammonia can enter the brain.

74
IAJPS 2018, 05 (03), 1831-1838
 Hypokalemia in ascites

• Hypokalemia  may result from excess urinary

potassium loss due to increased circulating
aldosterone, renal retention of ammonium ion in
exchange for potassium (K), secondary renal
tubular acidosis, or diuretic therapy.
• Management  consists of giving oral potassium
chloride supplements.

Systemic Abnormalities in Liver Disease

30
By Danielle Tholey , MD, Thomas Jefferson University Hospital
 Hyponatremia in cirrhosis

76
World J Gastroenterol. 2015 Mar 21; 21(11): 3197–3205.
 Paracentesis ascites
• To avoid hypovolemia, daily weight loss in patients with ascites
should not exceed 1000 g in the presence of peripheral edema or
500 g in the absence of peripheral edema [
Pockros and Reynolds, 1986].
• The diuretic effect is sufficient when only small amounts of ascitic
fluid remain and peripheral edema has disappeared completely.
• Complications of diuretic therapy include hepatic
encephalopathy, renal failure, gynecomastia, electrolyte
disturbances such as hyponatremia and hypokalemia or
hyperkalemia, and muscle cramps [Santos et al. 2003].
• To minimize these complications, it is advisable to reduce the
dosage of diuretic drugs after the mobilization of ascites.

77
Ther Adv Gastroenterol2015, Vol. 8(2) 83 –100
 78
CLINICAL LIVER DISEASE, VOL 7, NO 3, MARCH 2016
 Low SAAG in cirrhosis
• In a 2009 study of patients with cirrhosis and a low
SAAG, Khandwalla et al. found that only a minority of
these patients had a second cause (most commonly
peritonitis or peritoneal carcinomatosis).
• As such, the recommendation is to evaluate the other
usual peritoneal fluid studies (e.g. cell count/diff,
protein, cytology).
• If there is no clear secondary cause, it is reasonable to
repeat the paracentesis – the aforementioned study
found that on repeat testing, the SAAG often returned
to the expected level >1.1! 79
 Low SAAG in cirrhosis
• RESULTS
• We identified 92 patients (76 with cirrhosis and 16 with no
cirrhosis) with ascites and a SAAG of < 1.1 g / dl. Of the 76
patients with cirrhosis, only 29 (38 % ) had an identifiable cause,
most commonly primary bacterial peritonitis (11, 38 % ),
followed by peritoneal carcinomatosis or malignant ascites (8,
28 % ) and nephrotic syndrome (5, 17 % ).
• There were 47 patients with cirrhosis and a low SAAG for
whom no etiology was identified. Thirty-three patients
underwent a repeat paracentesis, 24 (73 % ) of whom changed
to a high SAAG.
• Most patients (65, 86 % ) had the serum and ascites albumin
levels measured < 12 h apart.
Am J Gastroenterol 2009; 104:1401 – 140 80
 Low SAAG in cirrhosis

• In summary, among patients with cirrhosis found to

have a low SAAG, the overall yield of a workup for
additional causes of low SAAG level is low.
• Standard workup for these patients should include
analysis of the ascitic fluid for cell count, bacterial
culture, albumin, and total protein.
• A repeat measurement should be performed, as
reversion to a SAAG of ≥ 1.1 g / dl is commonly
observe

Am J Gastroenterol 2009; 104:1401 – 140 81

 Low SAAG in cirrhosis
• diagnosis of SBP was based on bacterial growth in an ascitic fluid
collected in blood culture bottles inoculated at the bedside or an
ascitic absolute neutrophil count of at least 0.25 × 10 9 cells / l (8) .
• A diagnosis of secondary bacterial peritonitis was made if a
perforated viscus, intestinal ischemia, and / or obstruction were
documented by a radiographic or surgical evaluation.
• diagnosis of mycobacterial peritonitis required mycobacterial
growth in an ascitic fluid culture or peritoneal biopsy or positive
results of a polymerase chain reaction scan of ascitic fluid for a
mycobac-terium.
• Mycobacterial peritonitis diagnosis was also made if a
mycobacterial smear was positive in the presence of a positive
puri' ed protein derivative or if ascitic L uid adenosine deaminase
level was at least 40 IU / l (9)
Am J Gastroenterol 2009; 104:1401 – 140 82
 Low SAAG in cirrhosis
• We searched for commonly described etiologies for
low SAAG levels through ascites fluid analysis for
neutrophil count; bacterial and fungal culture; acid-
fast bacillus (AFB) culture; fluid cytology and
imaging modalities, including ultrasonography,
computerized tomography (CT), and magnetic
resonance imaging (MRI), to rule out malignancies,
peritoneal biopsy where indicated, and urine
protein measurement.
83
84
Dyserythropoiesis

Binucleated

85
 Dyserythropoiesis

Internuclear bridging

86
Dysgranulopoiesis

Pseudo pelger huet

87
Dysmegakaryopoiesis

88
 Meigs Syndrome
• Meigs syndrome is defined as the triad of benign ovarian
tumor with ascites and pleural effusion that resolves after
resection of the tumor. Ovarian fibromas constitute the
majority of the benign tumors seen in Meigs syndrome.
• Pseudo-Meigs syndrome consists of pleural effusion (an
example of which can be seen in the image below),
ascites, and benign tumors of the ovary other than
fibromas. These benign tumors include those of the
fallopian tube or uterus and mature teratomas, struma
ovarii, and ovarian leiomyomas. [4] This terminology
sometimes also includes ovarian or metastatic
gastrointestinal malignancies.
89
 Meigs Syndrome
• This supports the conclusion that Meigs’ syndrome
is associated with an exudate rather than a
transudate. It should be emphasized, however, that
a transudative pleural effusion does not rule out
Meigs’ syndrome.
• Exudative effusion in patients with Meigs’ syndrome
seems to be consistent with the mechanisms
involved in pleural fluid accumulation. It is believed
that the direct cause of pleural fluid formation is the
translocation of ascites via diaphragmatic pores.
90
 Meigs Syndrome
• Although the mechanism of peritoneal fluid
formation has not been fully explained, several
observations provide evidence that it may be linked
to inflammatory cytokines and growth factor
release, resulting in increased vascular permeability
and capillary leakage. Abramov et al found
extremely elevated serum, ascitic, and pleural fluid
levels of vascular endothelial growth factor (VEGF),
fibroblast growth factor (FGF), and interleukin-6 (IL-
6) in a patient with Meigs’ syndrome.
91
 Meigs Syndrome

• Other hypotheses on the mechanism of ascitic fluid

accumulation have also been formulated. Some
suggest that ascites results from stromal tumor
edema and transudation of interstitial fluid.

92
93
 Kriteria Light
Leukosit:
• <1000 sel/uL: transudat
• >1000 sel/uL: eksudat
• >10.000 sel/uL: keganasan/ trauma pd punksi pleura
• Pd cairan peritoneal leuko >500/uL predominan neutrofil>50% sesuai
kesan peritonitis bakteri.

Eritrosit
• Nilai hematokrit <1% tdk bermakna
• Ht>1%--rasiokan Ht pleura/Ht darah tepi
• Rasio Ht >0,5 : hematoraks
• Rasio 0,1-0,5 : keganasan pleura, emboli paru, efusi krn trauma
94
• Whenever ascites is sampled, a cell count should be
performed.
• This is a critical test to determine whether spontaneous
bacterial peritonitis is present.
• In patients with cirrhotic ascites, the presence of more
than 250 polymorphonuclear cells (PMNs) is consistent
with spontaneous bacterial peritonitis.
• The PMN count can also be elevated in pancreatic ascites,
but the SAAG in these patients will be less than 1.1 g/dL.

95
CLINICAL LIVER DISEASE, VOL 7, NO 3, MARCH 2016
• In patients with malignant-related ascites and peritoneal
carcinomatosis, cytology is positive in 96.7% of cases.
• However, in cases of hepatocellular carcinoma and cirrhosis, the
yield of cytology for malignancy is extremely low and is not
warranted.
• In cases where chronic infection is suspected, positive cultures
or peritoneal biopsy is required for the diagnosis.
• Ascites caused by chronic infections (e.g., tuberculosis and
filariasis) is more common in the Far East and developing
nations.
• Low serum oncotic pressure can also cause low SAAG ascites.
Testing for nephrotic syndrome and protein-losing enteropathy
should be performed in patients with low SAAG ascites and a
suspicion of either one of these conditions.
96
CLINICAL LIVER DISEASE, VOL 7, NO 3, MARCH 2016
 Myelodysplasia-Like Syndrome and
End-Stage Liver Disease Report of 2 Cases
Yi-Kong Keunga David Morganc David Hodgesb Melissa Blannc
Everardo Cobosa

• Case 1. A 50-year-old Latin-American female presented with anemic

symptoms since December 1996.
• The patient was admitted to this institution in May 1997 with mental
changes, and hepatic failure and encephalopathy were diagnosed.
• On admission, the ammonia level was 105 Ìmol/l (normal 9–33).
WBC was 3.5 ! 109/l, hemo- globin 10.4 g/dl, platelets 74 ! 109/l,
MCV 90.2 fl. Prothrombin time was prolonged to 15.5 s (normal 9.4–
11.8). Serum albumin was 2.6, total bilirubin 3.3 mg/dl, ALT was 35
and ALT 42 IU/l. Serum vitamin B12 and folate levels were normal.
• Hepatitis C virus RNA, HBsAg and ANA were negative.
97
Acta Haematol 2001;105:100–102
 Myelodysplasia-Like Syndrome and
End-Stage Liver Disease Report of 2 Cases
Yi-Kong Keunga David Morganc David Hodgesb Melissa Blannc Everardo
Cobosa

• Upper endoscopy revealed moderate esophageal varices

and portal hypertensive gastropathy.
• Bone marrow aspiration and biopsy showed hypercellular
marrow with erythroid dysplasia as reported in figure 1.
Iron staining was decreased. Abnormal localization of
immature precursors was present.

98
Acta Haematol 2001;105:100–102
 Myelodysplasia-Like Syndrome and
End-Stage Liver Disease Report of 2 Cases
Yi-Kong Keunga David Morganc David Hodgesb Melissa Blannc Everardo
Cobosa

• The bone marrow findings were interpreted as consistent

with refractory anemia according to the French-American-
British classification.
• The cytogenetic study of the bone marrow was normal
46,XX. ·1- antitrypsin quantitation was 79 mg/dl (normal:
45–180) but with MZ phenotype, suggesting heterozygous
·1-antitrypsin deficiency.
• The patient died of liver failure while being evaluated for
liver transplantation.
99
Acta Haematol 2001;105:100–102
 Myelodysplasia-Like Syndrome and
End-Stage Liver Disease Report of 2 Cases
Yi-Kong Keunga David Morganc David Hodgesb Melissa Blannc
Everardo Cobosa

• Case 2. A 50-year-old African-American female was diagnosed with

primary biliary cirrhosis since 1994.
• WBC then was 4.4 ! 109/l, hemoglobin 9.8 g/dl, platelets 67 ! 109/l.
• She was admitted to this institution 3 years later with hepatic
encephalopathy and severe pancytopenia.
• She was taking omeprazole, spironolactone, furosemide, and
cholestyramine.
• On admission, WBC was 1.6 ! 109/l, hemoglobin 6.1 g/dl, platelets 35
! 109/l, MCV 77 fl. Serum vitamin B12 and folate levels were normal.

100
Acta Haematol 2001;105:100–102
 Myelodysplasia-Like Syndrome and
End-Stage Liver Disease Report of 2 Cases
Yi-Kong Keunga David Morganc David Hodgesb Melissa Blannc
Everardo Cobosa

• Bone marrow examination revealed normocellular marrow with

erythroid and myeloid dysplasia.
• Iron staining was normal with no ringed sideroblast.
• Cytogenetic study of the bone marrow was normal 46,XX.
• She was treated conservatively.
• Her blood counts have remained relatively stable with WBC 3.3 !
109/l, hemoglobin 8.2 g/dl, platelets 53 ! 109/l.
• She is being evaluated for liver transplantation.

101
Acta Haematol 2001;105:100–102
 Patophysiology MDS
• It has been hypothesized that the pathogenesis of MDSs may lie in a
targeted injury to or mutations within multipotential hematopoietic
stem cells that are followed by immunologic responses that adversely
affect progenitor survival.
• This results in accelerated proliferation and premature death of
marrow cells amplified by apoptosis-inducing cytokines such as TNF-
α and Fas ligand.
• In MDSs, many proinflammatory cytokines have elevated expression,
and whether this is a primary or subsequent phenomenon is
uncertain.
• In MDS marrows, cells demonstrate impaired dif- ferentiation and
increased propensity to apoptosis, but as the disease progresses,
increased proliferation and decreased apoptosis occur, and
progression to AML can occur.
102
• Anemia – Anemia is almost uniformly present and is generally
associated with an inappropriately low reticulocyte response.
The mean corpuscular volume (MCV) may be macrocytic (>100
femtoliters) or normal. The red cell distribution width (RDW) is
often increased reflecting the presence of increased variability
in red cell size, also called anisocytosis. The mean corpuscular
hemoglobin concentration (MCHC) is usually normal, reflecting
a normal ratio of hemoglobin to cell size.

• Leukopenia – Approximately half of patients have a reduced

total white blood cell count (ie, leukopenia), usually resulting
from absolute neutropenia. Circulating immature neutrophils
(myelocytes, promyelocytes, and myeloblasts) may be
identified, but blasts constitute fewer than 20 percent of the
leukocyte differential. 103
• Thrombocytopenia – Varying degrees of
thrombocytopenia are present in roughly 25 percent
of patients with MDS. Unlike anemia, isolated
thrombocytopenia is not a common early
manifestation of MDS. However, a thrombocytopenic
presentation with minimal morphologic dysplasia has
been described in patients in whom del(20q) was the
sole karyotypic abnormality. Such patients may be
easily misdiagnosed as having immune
thrombocytopenia (ITP).

104
105
106
107
108
 JAMA. 2016;315(8):801-810. doi:10.1001/jama.2016.0287

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

197
0,99

70

456

0,5

TOTAL : 0 109
110
 Chole-acute renal failure

• Bile is normally excreated through biliary tract.

• When this route is blocked, kidney becomes the
main excretory pathway for biliary products.
Therefore, the jaundice patient is critically
dependent on kidney for survival.
• In such a situation if renal function declines due
to pre renal reasons, bilirubinemia mounts to
very high levels complicating established acute
renal failure
Indian J Nephrol 2001;11: 177-181 111
 Chole-acute renal failure
• Mechanism responsible for acute renal failure in
obstructive jaundice is multifactorial.
• Several factors have been implicated such as
– (i) endotoxemia
– (ii) hyperbilirubinemia
– (iii) increased serum levels of bile salts
– (iv) renovascular fibrindeposition
– (v) alterations in systemic and renal hemodynamics
– (vi) fluid depletion.

Indian J Nephrol 2001;11: 177-181 112

 Chole-acute renal failure
• Endotoxins derived from intestine seems to be the
cause of initial decline in GFR since systemic
endotoxemia has been demonstrated in 50% of
these patients in post operative period.
• Endotoxins act through liberation of cytokines
which alter renal hemodynamics apart from their
direct toxic action on kidneys.
• Cytokines also produce procoagulants leading to
DIC and fibrin deposition in glomerular capillaries
and peritubular capillaries.
• In obstructive jaundice, extracellular fluid depletion
also plays a major role in addition to endotoxemia.
113
Indian J Nephrol 2001;11: 177-181
 Diagnosis Criteria for Hepatorenal Syndrome

• Cirrhosis with ascites

• Serum Creatinine > 1.5 mg/dL
• Absence of shock
• No improvement of serum creatinine (decrease to a
level of 1.5 mg/dL or less) after at least 2 d of diuretic
withdraw and volume expansion with albumin.
• No current of recent exposure to nephrotoxic drugs
• Absence of parenchymal disease as indicated by
proteinuria >500 mg/dl, microscopic hematuria (50
RBC/HPF) and abnormal renal USG

Baraldi et al. Hepatorenal syndrome: Update on diagnosis and treatment. World J Nephrol 2015
Characteristics of type I and type II Hepatorenal
Syndrome
HRS Doubling of A precipitating No history 10%
I serum event is of diuretic survival in
creatinine in present in the resistant 90 day
<2wk most of case ascites without
treatment
HRS Renal No Always Median
II impairment precipitating ascites survival 6
gradually events diuretic month
progressive resistance
 Patophysiology CCA

International Journal of Hepatology Volume 2012, Article ID 630543, 7 pages116

 Cirrhosis and CCA
• Cirrhosis is a well-established risk factor for HCC; however, its
association with iCCA has not been well recognized, a recent
meta-analysis has shown that cirrhosis is, in fact, a risk factor
for iCCA with an overall odds ratio of 22.9 (95%CI: 18.2-26.8)
• This correlation was not fully acknowledged at the beginning
of the 20th century as Cirrhosis was not thought to be
related to CCA.
• Conversely, other studies have shown that around 24% of
patients with iCCA have a concurrent diagnosis of cirrhosis.
• In the chronic cases of cirrhosis, iCCA might be left
undiagnosed or misdiagnosed as HCC due to the chronic
inflammation of the liver which makes screening and
diagnosing patients with iCCA challenging.
Nov Appro Drug Des Dev 4(1): NAPDD.MS.ID.555634 (2018) 117
118
119
 Creatinin
Test principle
Enzymatic colorimetric method

120
 Creatinin
Test principle
Enzymatic colorimetric method
Icterus: No significant interference up to an I index of
15 for conjugated bilirubin (approximate conjugated
bilirubin concentration: 257 μmol/L (15 mg/dL)) or an
I index of 25 for unconjugated bilirubin
(approximate unconjugated bilirubin concentration:
428 μmol/L (25 mg/dL)).

Hemolysis: No significant interference up to an H

index of 800 (approximate hemoglobin concentration:
497 μmol/L (800 mg/dL)).
121
 Creatinin
Test principle
Enzymatic colorimetric method
Lipemia (Intralipid): No significant interference up
to an L index of 2000. There is a poor correlation
between the L index (corresponds to turbidity) and
triglycerides concentration.

Ascorbic acid: 1.70 mmol/L or <300 mg/L does not

interfere.

122
 Ascitic fluid analysis

123
IOSR Journal of Dental and Medical Sciences Vol 16, Issue 12 Ver. III (Dec. 2017), PP 01-07
• Because SAAG is proved to be superior to AFTP, AFLDH,
AFTP/STP, AFLDH/SLDH, serum cholesterol and ascitic
cholesterol, it should replace the total protein level as the
initial factor in classifying ascites.
• So all ascitic fluid samples should be classified as high gradient
or low gradient rather than as transudate or exudate.
• But AFTP has some value in specific circumstances.
• Patients with low AFTP are at high risk for SBP.
• In addition to assisting in classification of ascites, SAAG has
also importance in predicting response to treatment. Ascites
due to portal hypertension (eg. Cirrhosis) usually responds to
dietary sodium restriction and diuretics. Ascites unrelated to
portal hypertension (eg. Peritoneal TB) is refractory to diuretic
therapy.
124
IOSR Journal of Dental and Medical Sciences Vol 16, Issue 12 Ver. III (Dec. 2017), PP 01-07
Journal of Clinical and Translational 125
Hepatology 2014 vol. 2 | 58–64
 Ascitic fluid analysis
• Previous classification of Exudative and Transudative
Ascitis based on AFTP is unable to correctly identify the
aetiological factors and offers little insight to the
pathophysiology of ascitic fluid formation.
• It has been challenged in clinical conditions especially in
cirrhotic patients on prolonged diuretic theray, cardiac
ascites, malignant ascites, and Mixed ascitis like cirrhotic
patients with spontaneous bacterial peritonitis.
• SAAG classification is much more physiologic and
correlates well with the pathogenesis even in patients on
diuretic, cardiac ascitis and mixed ascitis.
International Journal of Research in Medical Sciences
Sastry AS et al. Int J Res Med Sci. 2017 Feb;5(2):429-436 126
 Ascitic fluid analysis
• Now Ascitis due to Malignancies are on rise and difficult to diagnose
by routine Ascitic fluid analysis. Althouh SAAG accurately differentiate
Ascitis due to Portal Hypertension from other causes, but SAAG is not
able to differentiate between malignant ascites and tuberculous
ascites as both are having low SAAG (<1.1 gm%).
• Fluid cytology has low sensitivity for malignancy as the differentiation
between reactive atypical mesothelial cells and malignant cells is
sometimes difficult.
• Most of the time, diagnosis in not possible without invasive and
expensive investigations like CT abdomen, Biopsy and FNAC of
peritoneal nodes and diagnostic laparotomy/laparoscopy. So there is a
need for more specific and a highly sensitive new marker in
presumptive diagnosis of ascites.
International Journal of Research in Medical Sciences
Sastry AS et al. Int J Res Med Sci. 2017 Feb;5(2):429-436 127
128
129
130
131
132
133
 Klatskin tumour

• The name Klatskin tumour from Gerald Klatskin, who

in 1965 described 15 cases and found some
characteristics for this type of cholangiocarcinoma.
• Klatskin tumours are cholangiocarcinomas localized in
the bifurcation of the common hepatic bile duct in the
liver hilum.
• The tumor is rare. The recent increase in incidence is
probably due to more accurate diagnostic procedures.
The tumours constitute approximately 30 percent of
the extrahepatic cholangiocarcinomas.

134
 Klatskin tumour

• The symptoms are progressive obstructive jaundice,

weight loss and pain. In the early stage of the disease
the diagnosis is difficult, as is preoperative histological
verification.
• Ultrasonography reveals dilated intrahepatic bile ducts
and a normal common duct. Sometimes the tumour in
the liver hilum can be seen and fine-needle biopsy
obtained. In nearly all cases transhepatic
cholangiography can verify the diagnosis. Evaluation of
resectability includes hepatic arteriography and
portography.
135
 Klatskin tumour
• The tumour is very rarely resectable when vessel
involvement is apparent.
• Resection of the tumour provides the only chance of
cure, but only 25 per cent of the tumours are resectable
and only half of these can be resected completely.
• Resection of the quadrate liver lobe facilitates
dissection, and hemihepatectomy is often necessary for
a curative resection.
• Surgical bypass and intubation may palliate jaundice, but
a similar palliation may be obtained by non-operative
biliary drainage by endoprostheses.

136
 Klatskin tumour

• The median survival for resected patients is

approximately 1 1/2 year.
• Median survival for patients with unresectable
tumours is less than 6 months and
insignificantly prolonged by palliative
procedures.

137
138
139
140
141
142
143
144
145
146
147
148
Determine ascites
Serum osmolality:
• (2x Na) + (BUN/2,8) + (Gluk/18)
• (2x 131) + ((30,80:2,14)/ 2,8) + (109/18)
• 262 + 5,14 + 6,05
• 273,19
 Classification Liver Cirrhosis
• Compensated cirrhosis
• In compensated cirrhosis, biochemical,
radiological, or histological findings consistent
with the pathological process of cirrhosis are
present with preservation of hepatic synthetic
function and no evidence of complications
related to portal HTN, such as ascites, gastro-
oesophageal varices and variceal bleeding,
hepatic encephalopathy, and/or jaundice.
Keith D. Lindor, MD
BMJ Best Parctice Cirrhosis
BMJ Publishing Group Ltd 2018. 152
 Classification Liver Cirrhosis
• Decompensated cirrhosis
• Cirrhosis is regarded as decompensated
when there is evidence of the development
of complications of liver dysfunction with
reduced hepatic synthetic function and
portal HTN including ascites, gastro-
oesophageal varices and variceal
bleeding, hepatic encephalopathy, and/or
jaundice.
Keith D. Lindor, MD
BMJ Best Parctice Cirrhosis
BMJ Publishing Group Ltd 2018. 153
158
159
160
 Inkubasi Fase Akut Fase Sembuh
Konvalesen
4-12 minggu 2-12 minggu 2-16 bulan Tahun

Total Anti-HBc

Anti HBs
Anti HBe
HBsAg

IgM Anti-HBc

HBeAg

Imunitas
Kontak
HBV DNA Window period

HBV- DNA , HBe Ag, HBs Ag muncul hampir bersamaan.

161
HBc Ag tidak terdapat diserum.
162
 Cause of false positive and false-negative
urinalysis results
Dipstick test False positive False negative
bilirubin Phenazopyridine Chlorpromazine
(pyridium) (thorazine), selenium
Blood Dehydration, exercise, Captopril, elevated
hemoglobinuria, specific gravity, pH
menstrual blood, <5.1, proteinuria,
myoglobinuria vitamin C
Glucose Ketones, levodopa Elevated specific
gravity, uric acid,
vitamin C
Ketones Acidic urine, elevated Delay in examination
specific gravity, of urine
mesna,
phenolphthalein, some
drug metabolite (e.g,
levodopa)
163
Leucocyte Containation Elevated specific gravity,
esterase glycosuria, ketonuria,
proteinuria, some oxiding
drugs (cephalexin,
nitrofurantoin,
tetracycline, gentamicin),
vitamin C

Nitrites Contamintaion Elevated specific gravity,

exposure of dipstick to elevated urbilinogen levels,
air, phenazopyridine nitrate reductase-negative
bacteria, pH < 6.0, vitamin
C

Protein Alkaline or Acidic or dilute urine,

concentrated urine, primary protein is not
phenazopyridine, albumin
quatemary ammonia
compounds 164
Protein Alkaline or Acidic or dilute urine,
concentrated urine, primary protein is not
phenazopyridine, albumin
quatemary ammonia
compounds
Specific Detran solutions, IV Alkaline urine
gravity radiopaque dyes,
proteinuria
Urobilinogen Elevated nitrite levels, -
phenazopyridine

165
 Dipstick urine
• BILIRUBIN AND UROBILINOGEN
• Urine normally does not contain detectable amounts of bilirubin.
Unconjugated bilirubin is water insoluble and cannot pass
through the glomerulus; conjugated bilirubin is water soluble and
indicates further evaluation for liver dysfunction and biliary
obstruction when it is detected in the urine.
• Normal urine contains only small amounts of urobilinogen, the
end product of conjugated bilirubin after it has passed through
the bile ducts and been metabolized in the intestine.
Urobilinogen is reabsorbed into the portal circulation, and a small
amount eventually is filtered by the glomerulus. Hemolysis and
hepatocellular disease can elevate urobilinogen levels, and
antibiotic use and bile duct obstruction can decrease urobilinogen
levels. 166
 Dipstick urine
• HEMATURIA
• According to the American Urological Association,
the presence of three or more red blood cells (RBCs)
per high-powered field (HPF) in two of three urine
samples is the generally accepted definition of
hematuria.18–20  The dipstick test for blood detects
the peroxidase activity of erythrocytes. However,
myoglobin and hemoglobin also will catalyze this
reaction, so a positive test result may indicate
hematuria, myoglobinuria, or hemoglobinuria.
167
168
169
170
171
172
173
 Hypokalemia
K+ redistribution True K+ deficit
• Insulin response Renal loss
• Alkalosis -Metabolic acidosis (RTA)
• Catecholamine or β- -ATN, diuretic phase, amphotericin
adrenergic excess toxicity, hypomagnesemia
• Pseudohypokalemia -Metabolic alkalosis
due to ↗ WBC - Extrarenal loss (diarrhea,
• Hypothermia sweating>)
• Hypokalemic periodic -↓dietary intake
paralysis

Rastergar A, Soleimani M. Hypokalaemia and hyperkalaemia. Postgraduate Medical

Journal. 2001 Dec 1;77(914):759-64. 174