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Physiology of Blood

RATNA KUSUMAWATI

DEPARTMENT OF PHYSIOLOGY, FACULTY OF MEDICINE


UNIVERSITAS SEBELAS MARET SURAKARTA
Body Fluid Compartments
Fungsi darah :
1. Transportasi: Mengangkut O2 dan CO2, nutrien, hormon, sisa
metabolisme. Menghantarkan panas ke luar tubuh

2. Regulasi : Mempertahankan homeostasis (mengatur pH, suhu,


tekanan osmotik/elektrolit)

3. Proteksi : melindungi kehilangan darah dan pertahanan tubuh


dari patogen/benda asing (antibodi, fagositosis, komplemen,
sitokin, dll)
Hemopoiesis
- Embryonic : up to 2 months
: Yolk sac
- Fetal : 2-7 months : Liver,
spleen, lymph nodes
- After birth : bone marrow
- Up to 5 years : bone
marrow almost bones
Haemopoietic growth factors
• GM-CSF
• Granulocyte-Macrophage colony stimulating factor
• M-CSF
• Macrophage colony stimulating factor
• Erythropoietin
• Erythropoiesis stimulating hormone
(These factors have the capacity to stimulate the proliferation of their target
progenitor cells when used as a sole source of stimulation)
• Thrombopoietin
• Stimulates megakaryopoiesis
Haemopoietic growth factors
• Cytokines
• IL 1 (Interleukin 1)
• IL 3
• IL 4
• IL 5
• IL 6
• IL 9
• IL 11
• TGF-β

• SCF (Stem cell factor, also known as kit-ligand)


Cytokines have no (e.g IL-1) or little (SCF) capacity to stimulate cell
proliferation on their own, but are able to synergise with other cytokines to
recruit nine cells into proliferation
Eritrocyte
- Biconcave disk  increase efficiency of gas exchange
- Unucleated  don’t have DNA  unable to repair damage
- Progress from blast precursors in the marrow over
periode of five days. Released into the blood as reticulocytes
 changes to erythrocytes in a day
-120 days  destroyed by RES
- Lack mitochondria  anaerobic metabolism (glikolisis)
- Flexible through capillary system
- Consist 280 million Hb molecule/eritrocyte. O2 bind to Hb
 difussion
- Hb binding nitrit oxide (NO) to regulate blood pressure &
blood flow
- Permeable to water, ion Na, Cl & K
FUNCTION OF RED BLOOD CELL
1. Transport of O₂
- from lung to tissue (Hb dependent)
2. Transport of CO₂
- from tissue to lung (depends on carbonic
anhidrase enzyme & Hb)
3. Acid-base balance
- through formation of bicarbonat HCO₃⁻ (ion
bicarbonat)
The effect of osmotic pressure on RBC :
- hypotonic  swell/burst
- hypertonic  shrink
- isotonic  normal
Erythropoiesis

Erythropoiesis
• controlled by hormones, especially erythropoietin (EPO) from
the kidney
• three phases of RBC maturation
• production of ribosomes
• synthesis of hemoglobin
• ejection of the nucleus and reduction in organelles
• leave bone marrow as reticulocytes  mature in the blood
stream to become erythrocytes
NECESSARY SUBSTANCES FOR ERYTHROPOESIS :
1. Iron
2. Cobalt
3. Manganese
4. Vit B1,B2, B6, B12, C, E
5. Folic acid
6. Amino acid
NECESSARY HORMON FOR ERYTHROCYTES REGULATION :
1. Erythropoietin
2. Tyroid hormone
3. Androgen
Nutritional Needs for Erythropoiesis
• iron - key nutritional requirement
• lost daily through urine, feces, and bleeding
• men 0.9 mg/day and women 1.7 mg/day
• low absorption rate of iron requires consumption of 5-20 mg/day
• dietary iron: ferric (Fe3+) and ferrous (Fe2+)
• stomach acid converts Fe3+ to absorbable Fe2+
• gastroferritin binds Fe2+ and transports it to small intestine
• absorbed into blood and binds to transferrin for transport
to bone marrow, liver, and other tissues
- bone marrow for hemoglobin, muscle for myoglobin,
and all cells use for cytochromes in mitochondria
• liver apoferritin binds to create ferritin for storage
Nutritional Needs for Erythropoiesis

• Vitamin B12 and folic acid


• rapid cell division and DNA synthesis that occurs in
erythropoiesis

• Vitamin C and copper


• cofactors for enzymes synthesizing hemoglobin
• copper is transported in the blood by an alpha globulin called
ceruloplasmin
• Yg berperan adl Vit B 12 & Asam folat
• Vit B12 & Asam folat penting utk sintesis DNA
Kekurangan Vit B12
& As.folat Penurunan DNA

Kegagalan pematangan & pembelahan inti

Sel2 eritroblastik gagal proliferasi dgn cepat

MAKROSIT
Erythropoiesis
Regulatioan
ERYTHROPOESIS
REGULATION
ERITROPOIETIN

• Merupakan faktor utama yg merangsang


produksi eritrosit
• Suatu hormon glikoprotein yg dibentuk dlm
ginjal (terutama) & hati
Erythrocyte Disorders
• polycythemia - an excess of RBCs
• primary polycythemia (polycythemia vera)
• cancer of erythropoietic cell line in red bone marrow
• RBC count as high as 11 million/L; hematocrit 80%
• secondary polycythemia
• from dehydration, emphysema, high altitude, or physical conditioning
• RBC count up to 8 million/L

• dangers of polycythemia
• increased blood volume, pressure, viscosity
• can lead to embolism, stroke or heart failure
Anemia
• causes of anemia fall into three categories:
• inadequate erythropoiesis or hemoglobin synthesis
• kidney failure and insufficient erythropoietin
• iron-deficiency anemia
• inadequate vitamin B12 from poor nutrition or lack of
intrinsic factor (pernicious anemia)
• hypoplastic anemia – slowing of erythropoiesis
• aplastic anemia - complete cessation of erythropoiesis
• hemorrhagic anemias from bleeding
• hemolytic anemias from RBC destruction (hemolitic)
RBC Life Span
HEMOGLOBIN &
MYOGLOBIN
O2 combines with Hgb in lungs
O2 gas not very soluble in H2O
Hemoglobin transports O2 Hemoglobin
• 2 α globin chains & 2 β globin chains
• 4 heme groups (lipid)
• each heme binds an iron ion (Fe²+) that carries 1 O2
O2 binding proteins:
myoglobin and hemoglobin
• oxygen is not water soluble  needs to
be transported
• diffusion is not effective
• myoglobin is found primarily in muscle
tissue
• Hemoglobin is in the blood
• Both proteins contain heme
Protein Function
Physiological roles of:
• Myoglobin
Transports O2 in rapidly respiring muscle
Store of O2 in muscle high affinity for O2
keep O2 supplied to muscles
• Hemoglobin
Found in red blood cells
Carries O2 from lungs to tissues and removes CO2
and H+ from blood to lungs
Lower affinity for O2 than myoglobin
Tetrameter - two sets of similar units (22)
Strong form of hemoglobin found in embryos
Takes oxygen from mother’s hemoglobin
Myoglobin, The Muscle’s O2 Store
• Myoglobin is an iron-containing globular protein in
skeletal and cardiac muscle.
• Stores O2 intramuscularly
• Myoglobin contains only 1 iron atom.
• O2 is released at low PO2.
Myoglobin Binding Curve
• Hyperbolic binding curve
• Relatively insensitive to small
changes in oxygen
concentration
• Hb molecules of O2combine max with 4,
in cascade manner (100% saturated)
• Oxygenation  each binding facilitates
further binding of O2
• Saturation of Hb  refers the number of
O2 molecules combined with Hb
• 50% saturation : means that Hb binds
with 2 molecules of O2
Transport of O2 in the Blood
• Two mechanisms exist for O2 transport
• Dissolved in plasma
• Combined with hemoglobin

• PO2 and Hb Saturation


Oxyhemoglobin dissociation curve illustrates the
saturation of Hb with oxygen at various PO2 values
Bohr Effect
• Conditions creating the Bohr effect
• Increased PCO2
• Increased temperature
• Increased 2,3-DPG
• Decreased pH
• Cause a shift to the right of the oxyhemoglobin
dissociation curve
CO2 Transport as Bicarbonate
• CO2 in solution combines with water
to form carbonic acid.
• Carbonic anhydrase
• Zinc-containing enzyme within red
blood cell
• Carbonic acid ionizes into hydrogen
ions and bicarbonate ions.
Leukocytes/White Blood Cells
• 5 types
• Basophils
• Eosinophils
• Neutrophils
• Monocytes
• Lymphocytes
Types and Functions of
Leukocytes
TYPE CELL FUNCTION
Granulocytes
Neutrophil Phagocytosis, early phase of
inflammation
Eosinophil Phagocytosis, parasitic infections
Basophil Inflammatory response, allergic
response
Agranulocytes
Lymphocyte Cellular, humoral immune response
Monocyte Phagocytosis; cellular immune
response
Leukocytes (WBCs)
• least abundant formed element
• 5,000 to 10,000 WBCs/L

• protect against infectious microorganisms and other


pathogens
• conspicuous nucleus
• spend only a few hours in the blood stream before migrating
to connective tissue
• retain their organelles for protein synthesis
• granules
• all WBCs have lysosomes called nonspecific (azurophilic) granules –
inconspicuous so cytoplasm looks clear
• granulocytes have specific granules that contain enzymes and other
chemicals employed in defense against pathogens
Types of Leukocytes
• granulocytes
• neutrophils (60-70%)-polymorphonuclear leukocytes
• barely-visible granules in cytoplasm; 3 to 5 lobed nucleus
• eosinophils (2-4%)
• large rosy-orange granules; bilobed nucleus
• basophils (<1%)
• large, abundant, violet granules (obscure a large S-shaped nucleus)

• agranulocytes
• lymphocytes (25-33%)
• variable amounts of bluish cytoplasm (scanty to abundant);
ovoid/round, uniform dark violet nucleus
• monocytes (3-8%)
• largest WBC; ovoid, kidney-, or horseshoe- shaped nucleus
Physiological Characteristics and Functions of
Leukocyte

Terminology

• Diapedisis: Metamorphosed WBCs pass through vessel wall getting into


interstitial fluid.

• Chemotaxis: It is a process that WBCs shift to some chemical material


(metabolic production, antigen-antibody complex, bacteria, toxin, etc).

• Phagocytosis: It is a process that WBCs enclose and engulf exotic or


extraneous material, and use intracellular enzyme digesting them.
Neutrophil
• Another name, polymorphonuclear, PMN, 6~8 h in the vessels,
diapedisis, chemotaxis and phagocytosis (using its hydrolyzed
enzyme)
• Function: It plays a very important role in nonspecific cellular
immunity system which is against pathogenic microorganism, such
as bacteria, virus, parasite, etc.
• Clinic relation:
Number of neutrophil greatly increase occurring in
acute inflammation and earlier time of chronic
inflammation.
number decrease of neutrophil will result in poor
resistibility and easily suffering from infection.
Neutrophil kinetics
Eosinophil
Circadian changes: Its number is lower in the morning
and higher at night.
 Function:
1. It limits and modulates the effects of basophil on fast
allergic reaction.
2. It is involved in immune reaction against worm with
opsonization.
 Clinic relation: Its number increase when person suffers
from parasite infection or allergic reaction.
Basophil
Circulatory time: 12 hours
 Basogranules contain heparin, histamine, chemotactic
factors and chronic reactive material for allergic reaction.
 Function: It is also involved in allergic reaction.
1. Heparin serves as lipase cobase and speeds up fatty
decomposition.
2. Histamine and chronic reactive material increase
permeability of capillary and contract bronchia smooth
muscle, and result in allergic reaction such as measles,
asthma.
3. Eosinophil chemotactic factor A released by basophil
can attract eosinophil collection and modify eosinophil
function.
Monocyte
Its body is large, diameter about 15~30 µm without granule
Function:
1. It contains many nonspecific lipase and displays the
powerful phagocytosis.
2. As soon as monocytes get into tissue from blood , it change
name called macrophage activating monocyte- macrophage
system to release many cytokins, such as colony stimulating
factor (CSF), IL-1, IL-3, IL-6, TNFα, INF-α,β ,etc.
3. Cytokins induced by monocyte may modulate other cells
growth.
4. Monocyte- macrophage system plays a very important role in
specific immune responsive induction and regulation.
Lymphocyte

Classification: It can be separated into T- Lymphocyte and


B- Lymphocyte.
 Function:
1. Lymphocytes serve as a nuclear role in immune
responsive reaction.
2. T- Lymphocytes involved in cellular immunity.
3. B- Lymphocytes involved in humoral immunity.
 Clinic relation: Numbers increase of lymphocytes occur
in chronic inflammation and late time of infection.
Lymphopoiesis
Leukocyte Life Cycle
• leukopoiesis – production of white blood cells
• pluripotent stem cells – (PPSCs)
• myeloblasts – form neutrophils, eosinophils, basophils
• monoblasts - form monocytes
• lymphoblasts give rise to all forms of lymphocytes
• red bone marrow stores and releases granulocytes and monocytes
• circulating WBCs do not stay in bloodstream
• granulocytes leave in 8 hours and live 5 days longer
• monocytes leave in 20 hours, transform into macrophages and live for several
years
• lymphocytes provide long-term immunity (decades) being continuously
recycled from blood to tissue fluid to lymph and back to the blood
Summary :
Granulocyte Functions
• neutrophils - increased numbers in bacterial infections
• phagocytosis of bacteria
• release antimicrobial chemicals

• eosinophils - increased numbers in parasitic infections, collagen


diseases, allergies, diseases of spleen and CNS
• phagocytosis of antigen-antibody complexes,
allergens, and inflammatory chemicals
• release enzymes to destroy large parasites

• basophils - increased numbers in chicken pox, sinusitis, diabetes


• secrete histamine (vasodilator) – speeds flow of blood to an injured area
• secrete heparin (anticoagulant) – promotes the mobility of other WBCs in
the area
Summary :
Agranulocyte Functions
• lymphocytes - increased numbers in diverse
infections and immune responses
• destroy cells (cancer, foreign, and virally infected cells)
• “present” antigens to activate other immune cells
• coordinate actions of other immune cells
• secrete antibodies and provide immune memory

• monocytes - increased numbers in viral infections


and inflammation
• leave bloodstream and transform into macrophages
• phagocytize pathogens and debris
• “present” antigens to activate other immune cells - antigen
presenting cells (APCs)
TERIMA KASIH

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