REFRESH

Typical changes of CRP, fibrinogen, ESR and albumin

during an acute phase reaction
Stein B, Fuster V, Israel DH, et al. Platelet inhibitor agents in cardiovascular disease: an update. J Am Coll Cardiol. 1989;14:813–836.
 PROSES KOAGULASI – CASCADE / WATERFALL
F XII
Pencetus Pre Kalikrein

EKSTRINSIK
JALUR INTRINSIK

HMWK
F VII

JALUR
F XI
Pencetus
F XII a Kalikrein
Ion Ca
F VII a
HMWK F IX
APTT - CT

F XI a
Ion Ca F IX a

PT
F IX a – PF 3 – F VIII – Ion Ca

FX F Xa

F X a – F V – PF 3 - Ion Ca Fibrinogen
BERSAMA
JALUR

Protrombin Trombin
Fibrin

TT
F XIII F XIII a
Fibrin Insoluble
 PROSES KOAGULASI

INJURY IX

XI a
IX IX a
VIIa
TF XI
TFPI VIII a

X Xa
Va Thrombin activation
Prothrombin Thrombin

Fibrinogen Fibrin
 FIBRINOLISIS
F XIII
Trombin

AT III F XIII a

Fibrin Cross
Fibrinogen
Monomer Linked
2 Anti Fibrin
plasmin Plasmin 2 Anti
plasmin
FDP t PA
Uro PAI-1 D Dimers

Plasminogen
 Fibrinogenolysis Fibrinolysis
Thrombin
D D
Fibrinogen Cross-linked fibrin
Plasmin

X
X-oligomer
Y
D

D E D-dimer E

Single fragments
Plasmin cleavages of fibrinogen and fibrin E D-Dimer

2004-02-03(tb\pp\ovhd04) Axis-Shield PoC AS 1

 Sites of Haemopoiesis
• Yolk sac

• Liver and spleen

• Bone marrow
– Gradual replacement
of active (red) marrow
by inactive (fatty)
tissue
– Expansion can occur
during increased need
for cell production
Cell hierarchy (Haemopoiesis schematic
representation)
Life cycle of red blood cells.
Neutrophil kinetics
 PSC
TPO
CFU
GEMM
IL-3, IL-6, IL-11, GCSF, TPO
CFU
MEG
TPO, EPO , IL-3, IL-6, IL-11
IMM.MEG
M.BLAST 7 – 10 hari
TPO, IL-6, IL-11,

MEGAKA
RIOSIT

TPO 1/ 3 KE LIMPA
4000 TROMBOSIT 36 JAM
KORTIKOSTEROID

faal_imun/ikun/2006 19
faal_imun/ikun/2006 21
Staging of CLL according to Rai (1975)
 Causes of icterus
Icterus (jaundice) :
bilirubin darah > 10 mg/l (hyperbilirubine-mia)  kuning
o Pre-hepatic : haemolysis (haemolytic anaemia, neonatal
jaundice)  overproduksi bilirubin  unconjugated bilirubin in
blood and urobilinogen in urine

o Hepatic : liver damage (hepatitis, cirrhosis)   kemampuan

metabolisme bilirubin (uptake, conjugation, excretion) 
 bilirubin D & In di darah, urobilinogen in urine  
microobstruction  menurunnya enterohepatic cycle.

o Post-hepatic : obstruction biliari  birubin direk regurgitasi di

hepatic veins and lymphatics   conj. bilirubin in blood,
urobilinogen in urine 
Increased red cell
breakdown.
o Serum bilirubin-
unconjugated 
o Urine Urobilinogen 
o Faecal Stercobilinogen 
o Haemoglobinaemia,
haemoglobinuria,
haemosiderinuria
 Interdependence of Cardiac Biomarkers
Pathophysiology Biochemical Markers
Coronary artery disease Risk factors (eg, cholesterol)

Coronary inlammation CRP, homocysteine, MPO

Plaque instability/disruption MPO, Lp(a)

Myocardial ischemia/necrosis Cardiac troponins, CK-MB, myoglobin

Ventricular overload BNP, Nt-proBNP

Adapted from Panteghini. Eur Heart J. 2004;25:1187-1196.

26/42
 Taylor, FB, et al. Thromb Haemost 2001;86:1327

Overt DIC Scoring System

 KUALIFIKASI PETANDA TUMOR
PENGGUNAAN
JENIS MARKER CONTOH
UTAMA
CEA Kolon, Hepatoma
Antigen Onkofetal
AFP Germ cell tumor
PSA Prostat
CA 125 Ovarium
Cancer Related Ag
CA 15.3 Payudara
CA 19.9 Pankreas
Antigen Cel T & B Leukemia & Limfoma
CD
Antigen Myeloid Leukemia
PSA, PAP Prostat
Komponen sel normal
LDH Limfoma
Paraproteinemia &
Immunoglobulin Ig : A, G, M, D, E
limfoma
Beta HCG Korio Ca, Germ cel
Hormon
Calcitonin Tiroid
 UJI SARING PENANDA TUMOR

PENANDA TUMOR SASARAN SKRINING

PSA (Prostate Specific Pria berusia > 50 tahun,

Antigen) Untuk deteksi kanker prostat

HPV - DNA Pada pasien dengan hasil

Pap smear “inconclusive”

IgA anti EBV-VCA/EA Pada pasien berisiko tinggi

terkena kanker nasofaring

AFP Pada penderita hepatitis kronis

untuk deteksi kanker hati
 BAGAN TUMOR MARKER
JENIS KANKER SKRINING DIAGNOSIS PROGNOSIS PEMANTAUAN PENGOBATAN
& DETEKSI KEKAMBUHAN
T.Sel Germinal - AFP, HCG, LDH AFP, HCG, LDH AFP, HCG, LDH, PLAP
Kolorektal Darah Samar - CEA CEA, CA 19-9
Payudara - - ER, PR, cErb2 CA 15-3, MCA, CEA, CA 27.29
Ovarium - CA 125, CA 72-4 CEA, CA 125
CEA/CA 19-9, AFP, HCG
Prostat PSA (+ DRE) PSA (+ DRE), f-PSA PSA, f-PSA PSA
Paru - NSE, Cyfra 21-1 - Cyfra 21-1, CEA, NSE
Tiroid Thyroglobulin, Calcitonin Thyroglobulin, Calcitonin
MultipleMyeloma SPE, Imunoelek, b2-mikro b2-mikroglobulin SPE, imunoelek, b2-mikroglog
Neuroblastoma Cathecolamin, VMA, NSE - NSE
Hati AFP AFP, PIVKA II - AFP
Pankreas - CA 19-9, CEA CA 19-9 CA 19-9
Lambung - - CA 72-4 CA 72-4, CA 19-9, CEA
Nasofaring IgA EBV-VCA/EA IgA anti EBV VCA - IgA anti EBV-VCA
Esofagus - CEA, SCC - -
Serviks HPV-DNA - - SCC
 THALASSEMIA : Penyakit genetik
Defek sintesis Hb

Molekul Hemoglobin Komposisi

Hb dewasa
heme

 b


heme 
HbA (2b2) 98%
Thalassemia-: sintesis rantai globin-  atau ()
HbA2 (22) ~ 2.5%
Thalassemia-b: sintesis rantai globin-b  atau () HbF (22) <1%
 DIAGNOSIS IN THE DEVELOPMENT OF IRON DEFICIENCY ANAEMIA

Hemoglobin Serum iron TIBC Saturation Serum ferritin RBC

(g/dL) (ug/dL) (ug/dL) (%) (ng/mL) morphology
Stage 1
Iron depletion N N N or  N  Normochromic,
normocytic

Stage 2
Iron deficient N     Normochromic,
erythropoiesis normocytic

Stage 3A
Iron deficient      Normochromic,
anaemia normocytic

Stage 3B
Iron deficient      Hypochromic,
anaemia microcytic

Normal 13 – 16 35 – 150 260 – 400 20 – 45 30 – 400 Normochromic,

normocytic
12 – 14 35 – 150 260 – 445 20 – 45 13 – 150 Normochromic,
normocytic
PATOGENESIS SEPSIS

39
SIKLUS HIDUP
TOXOPLASMA

Siklus
Hidup
HIV life cycle
Steps in HIV Infection and Pathogenesis
 Respon Immun terhadap Infeksi HIV

• Terdapat respon humoral dan cell-mediated immune responses

specific pada pasien yg terinfeksi HIV.
• CTL respons thd HIV terdeteksi 2-3 minggu setelah infeksi awal 
puncak : minggu 9-12, dilanjutkan ekspansi yg nyata dari klon virus-
specific CD8+ T cell .
• Respon imun humoral mencapai puncaknya pada minggu ke-12.
 Curve of pancreatic enzymes

amylase
IU/L

trypsin

lipase

2 hrs 4 hrs 8 hrs 12 hrs 72 hrs 3 days 7 days 14 days

SIMPTOMS
 Perjalanan Infeksi HIV
• Segera setelah virus masuk ke
aliran darah, HIV mulai
replikasi secara cepat, dan
viral load meloncat tajam
• Banyak sel CD4 dihancurkan
 jumlah sel CD4 turun
drastis.
• Setelah bbrp minggu, sistem
imun mulai membentuk
antibodi thd HIV  viral load
mulai menurun dan jumlah
CD4 meningkat kembali.
• Antibodi baru dapat terdeteksi
setelah beberapa minggu.
Pada masa ini, viral load dan
daya menular paling tinggi.
• Kelanjutan infeksi setelah
infeksi akut.
• Tahap ini biasanya mulai
dengan masa tanpa gejala, yg
bertahan rata-rata 7-10
tahun/lebih/kurang.
• Selama masa ini viral load
meningkat pelan-pelan,
sementara jumlah CD4 terus-
menerus merosot
• HIV replikasi terus kemudian
viral load mulai meningkat
tajam, sementara jumlah CD4
menurun < 200/mm3 
didefinisikan AIDS.
1
7
3

7
4
6

2 5
Normal catabolism
of aged RBCs

50
Intravascular
hemolytic
anemia

51
Removal of hemoglobin from blood plasma after intravascular hemolysis
Lysed RBC
In blood vessel

α/β dimers

Kidney

Hemoglobinuria
Hemosiderinuria
Urobilinogenuria

52
Extravascular
hemolytic
anemia

53
Intravascular hemolytic anemia
Serum:
• increased unconjugated &bilirubin
• increased urobilinogen
• increased LDH activity
• absence of haptoglobin
• decreased glycosylated hb
• increased free hb
• increased methemalbumin
• decreased hemopexin
•
Urine
• increased urobilinogen (urobilinogenuria)
• positive free hb (hemoglobinuria)
• positive methemoglobin
• hemosiderinuria
Stools
• Fecal urobilinogen

Coomb’s test : + (positive) 54

Extravascular hemolytic anemia

Serum:
• increased unconjugated bilirubin
• increased conjugated bilirubin
• increased urobilinogen
Urine
• increased urobilinogen
•
Stools
• increased urobilinogen

Coomb’s test : + (positive)

55
 Laboratory characterization of AIHA

Laboratory parameter Warm type Cold type

Usual Ig type IgG IgM
DAT
Monospecific sera:
- Anti-Ig only 1+ 0
- Anti-IgG + anti-C1 1+ 0
- Anti-C1 only Rare 1+
Complement activation Little or more Yes

Serum complement levels N or decrease Decrease

Osmotic fragility Increase Normal

Peripheral blood findings Spherocytes, RBCs
NRBCs agglutination
56
 HYPERBILIRUBINEMIA
 Increased plasma concentrations of bilirubin (> 3 mg/dL) occurs when
there is an imbalance between its production and excretion
 Recognized clinically as jaundice
The Pancreas
 Acute Pancreatitis
RANSON criterias:
Initial 24 hours: Subsequent 48 hours:
• Age > 55 y.o. • PaO2 < 60 mHg
• Glucose > 200 mg/dl • BUN > 8 mg/dl
• WBC > 16.000/ml • Ca < 8 mg/dl
• LDH > 350 IU/L • Base deficit > 4 meq/L
• AST > 250 IU/L • Estimated fluid sequestration >
6L
• Fall in Hct>10%.
Mortality rate:
A. < 3 signs = 1%
B. Three to four signs = 11%.
C. Five to six signs = 33%
D. > 6 signs = 100%.
 Curve of pancreatic enzymes

amylase
IU/L

trypsin

lipase

2 hrs 4 hrs 8 hrs 12 hrs 72 hrs 3 days 7 days 14 days

SIMPTOMS