3. OXYGEN DELIVERY
• In the normal state (blue line), oxygen
consumption is constant over a range of
DO2, and decreases only when DO2 falls
below a critical level (critical DO2).
• Pathologic changes caused by sepsis or
SIRS (red line) cause increased VO2 and
impaired peripheral oxygen utilization,
resulting in an elevation in critical DO2.
Pathologic state
Normal state
Oxygen
consumption
(VO2)
Oxygen delivery (DO2)
DO2 = HR x SV x (1.34 x Hb x SaO2) + (0.003 x PaO2) x 10
4. ANEMIA
Definisi Anemia:
Sindroma klinis yang disebabkan penurunan massa eritrosit total dalam tubuh.
Keadaan dimana massa eritrosit dan atau massa hemoglobin tidak dapat memenuhi fungsinya
untuk menyediakan oksigen bagi jaringan tubuh
Penurunan di bawah normal kadar Hb, hitung eritrosit, dan hematocrit
Robbins, Buku Ajar patologi. Jakarta: Penerbit Buku Kedokteran EGC.2007
5. WHO DEFINITION OF ANEMIA
World Health Organization, 2011. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity (No. WHO/NMH/NHD/MNM/11.1). World Health Organization.
AGE Hb gr/dL
6/12 - 6 yrs <10
6 - 14 yrs <12
Adult male <13
Non pregnant female <12
Pregnant female
1st trimester <11
2nd trimester <10.5
HO 2016. Availabe at https://www.who.int/health-topics/anaemia
7. KLASIFIKASI ANEMIA
Berkurangnya produksi
sel darah merah
Meningkatnya destruksi
sel darah merah
Kehilangan darah
Pendekatan
Kinetik
Amaylia O, CDK-194/vol. 39 no. 6 th.2012. RSHS. Bandung. 2012
14. PENDEKATAN DIAGNOSIS
ANEMIA - RPI
Jameson LJ, et al. Harrison’s Principles of Internal Medicine. 20th Ed. New York:McGraw-Hill Education. 2018.
15. PATOFISIOLOGI ANEMIA
penurunan kapasitas dari darah
dalam membawa oksigen
hipoksia jaringan
kompensasi dari sistem kardiovaskular, respirasi dan
hemologik
McCance KL. Structure and function of Hematologic System. In: McCance KL, editor. Pathophysiology: The Biologic
basiis for disease in Adults and Children. 2006.
16. SIGNS AND SYMPTOMS
Cain SM et al. Acute lung injury. Assessment of tissue oxygenation. Crit Care Clin 1986; 2:537.
Leach, R. M., & Treacher, D. F. (1998). Oxygen transport2. Tissue hypoxia. Bmj, 317(7169), 1370-1373.
18. Dietary Iron Intake
Organic Iron
Fe++ or Fe2+
An-organic Iron
Fe+++ or Fe3+
Heme Iron Non-heme
Iron
Ganz T and Nemeth E. Nature Rev Immunol. 2015;July:1-11. Advance online publication:
20. PATOFISIOLOGI ANEMIA
DEFISIENSI BESI
Camaschella, C. (2015). Iron-deficiency anemia. New England journal of medicine, 372(19), 1832-1843.
2+
Fe3+
Vit C
Ferri reductase
Heme iron
HCP-1
HCP-1: Heme Carrier Protein-1
DMT1: Dimetal Transporter-1
FPN: Ferroportin
Labile iron pool (Fe3+)
Ceruloplasmin
Haephaestin
Transferrin
70%
30%
Ferritin
24. IRON DEFFICIENCY ANEMIA
EPO
HAMP
HFE TRF-1 HFE TRF-2 HJV BMP6
Bleeding
Erythroferrone (ERFE)
TMPRSS6
Adapted from Camaschella C. N Engl J Med. 2015;(19):1832–43.
Serum Fe
Transferrin
Tf Saturation
Ferritin
Hepcidin
Ferroportin
DMT-1
Heme Iron
Ferrous iron (Fe2+)
Ferric iron (Fe3+)
Labile Iron Pool (LIP)
Ferroportin
Transerrin Receptor
STEAP
25. Anemia of Inflammation (Anemia of
Chronic Disease)
Hepcidi
n
IL-6
IL-10
EPO IL-1
TNF-α
Serum Fe
Transferrin
Tf Saturation
Ferritin
Hepcidin
Ferroportin
Tf receptor
N/
Weiss G and Goodnough LT. N Engl J Med 2005;352:1011-1023.
Heme Iron
Ferrous iron (Fe2+)
Ferric iron (Fe3+)
Labile Iron Pool (LIP)
Ferroportin
Transerrin Receptor
STEAP
In the normal state (blue line), oxygen consumption is constant over a range of DO2, and decreases only when DO2 falls below a critical level (critical DO2).
Pathologic changes caused by sepsis or SIRS (red line) cause increased VO2 and impaired peripheral oxygen utilization, resulting in an elevation in critical DO2.
Eritrosit ukurannya kurang lebih sama dengan inti limfosit kecil
Central pallor is less
than one third of the cell diameter
Figure 1. The Iron Cycle — Mechanisms of Adaptation to Iron Deficiency. The mechanisms of adaptation to iron deficiency are centered on the suppression of the hepatic hormone hepcidin
and the tissue hypoxia that develops consequent to anemia. The production of erythropoietin (EPO) by the kidney increases in response to enhanced levels of hypoxia-inducible factor 2α (HIF-2α). As a consequence of the stimula- tion of erythropoietin, erythropoiesis is increased and hypochromic microcytic red cells are produced owing to the low availability of iron. Senescent red cells are destroyed by macrophages, and their iron is recycled. The increase in erythropoiesis suppresses the production of hepcidin. In mice, this function is mediated by erythroferrone (ERFE), which is secreted by the erythroblasts21 to maintain adequate iron absorption and efficiency in erythropoiesis. HIF-2α increases the expression of the duodenal divalent metal transporter 1 (DMT1)22 on the apical surface of enterocytes to increase the transfer of dietary iron from the lumen to enterocytes. Hepcidin levels are depressed in response to a reduction in the physiologic signals that maintain its production (e.g., increases in levels of iron-bound transferrin and in the iron content of the liver),2,18 to the increased activity of the inhibitor transmembrane protease, serine 6 (TMPRSS6),23 to the reduction in levels of the activator bone morphogenetic protein 6 (BMP6), and to increased in- hibition from erythropoietin-stimulated erythropoiesis. Ferroportin (FPN), which is no longer being degraded because of the low levels of hepcidin, exports the available iron across the enterocyte basal membrane and from macrophage stores17 to the circulation. Once stores are exhausted, levels of circulating iron decrease, even if absorption from the lumen is increased. Reduced levels of iron in the liver trigger increases in the synthesis of the iron carrier transferrin (referred to as apotransferrin when not bound to iron), further decreasing levels of iron-bound transferrin, the ligand of the transferrin receptor. Consequently, the uptake of iron from transferrin receptors by all cells and organs (e.g., skeletal muscles and the heart) is reduced.
Normally, iron is absorbed in the gastrointestinal tract and is delivered to transferrin for transport to the developing red cells, with any excess stored in hepatocytes. In inflammatory states, decreased absorption of iron leads to reduced saturation of transferrin and impaired release of iron from storage, resulting in a lack of iron delivery to the developing red cells. These changes are mediated by hepcidin, which binds and in- hibits ferroportin, the main iron-export protein. DMT1 denotes divalent metal transporter 1
