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9/6/2022

 the cell membrane is a dynamic fluid structure with globular


proteins floating in lipids. The lipids, as phospholipids, are
arranged in two layers.
 The polar (charged) phosphate ends of the
 asthe smallest organized units of living tissues, have phospholipids are oriented toward the inner and outer
the ability to individually perform all the functions surfaces, while the nonpolar (fatty acid) ends point
essential for life processes. Although the range of toward each other in the interior of the membrane.
morphological features varies widely, all cells
 Protein molecules may be either integral (incorporated into
conform to a basic mode. the lipid bilayer) or peripheral (associated with either the
outer or the inner surface of the membrane).
 Polysaccharides in the form of either glycoproteins or
glycolipids can be found attached to the lipid and
protein molecules of the membrane.
CELLS
CELLULAR MEMBRANES:
STRUCTURE (THE FLUID MOSAIC MODEL)

 Osmosis is used to describe the net movement of water


molecules through a semipermeable membrane.
Normally, water molecules move in and out of the cell
 Thelipid bilayer is directly responsible for the membrane at an equal rate, producing no net
movement.
impermeability of the membrane to most water-
soluble molecules.  If a concentration gradient exists, the movement of
water molecules will be greater from areas of low solute
 Membrane-bound carbohydrates act as surface (e.g., sodium and chloride ions) concentration to areas
antigens, which function in the process of cellular of higher solute concentration.
recognition and interaction between cells.
 Osmosis is the basic principle underlying the previously
popular erythrocyte, or red blood cell, fragility test that
demonstrates changes in the erythrocytic membrane.
Alterations in the erythrocytic membrane, such as the loss
MEMBRANE FUNCTIONS of flexibility, can be observed by placing erythrocytes in
solutions with varying solute concentrations
MEMBRANE FUNCTION: OSMOSIS

 Diffusion is an important process in overall cellular


physiology, such as the physiological activities of the
erythrocyte.
 This passive process through a semipermeable membrane
may also be referred to as dialysis. Substances passively
diffuse, or move down a concentration gradient from
areas of high solute concentration to areas of low solute
concentration, by dissolving in the lipid portion of the
cellular membrane.
 Diffusion through the membrane is influenced by the
solubility of molecules in lipids, temperature, and the
concentration gradient. Lipid-soluble substances diffuse
through the lipid layer at rates greater than through the
protein portions of the membrane
OSMOSIS IN RED BLOOD CELLS
MEMBRANE FUNCTION: DIFFUSION

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 Active transport is another essential membrane function.


 Small molecules, such as those of water or inorganic ions, are Because the cellular membrane also functions as a metabolic
able to pass down the concentration gradient via hydrophilic regulator, enzyme molecules are incorporated into the
regions. These hydrophilic regions are associated with the points membrane. One such enzyme, particularly important as a
where some of the membrane’s protein molecules create a metabolic regulator, is sodium-potassium-adenosine
polar area, resulting in pore-like openings. However, movement triphosphatase (Na-K-ATPase).
of molecules through these regions is affected by electrical  This enzyme provides the necessary energy to drive the sodium-
charges along the surface of the region, the size of the region, potassium pump, a fundamental ion transport system. Sodium
and the specific nature of the protein. Calcium ions affect the ions are pumped out of the cells into extracellular fluids, where
permeability of membranes. An increase in the concentration of the concentration of sodium is higher than it is inside the cell. This
calcium ions in the fluid surrounding the cell, or accumulation of movement of molecules is referred to as moving against the
calcium ions in the cytoplasm, can decrease the permeability of concentration gradient.
the membrane and has been demonstrated as a factor in the
aging process of erythrocytes
MEMBRANE FUNCTION: ACTIVE
TRANSPORT
MEMBRANE FUNCTION: HYDROPHILIC
REGIONS

 Anaplasia—highly pleomorphic and bizarre cytologic features


 Endocytosis is the process of engulfing particles or molecules,
associated with malignant tumors that are poorly differentiated.
with the subsequent formation of membrane bound vacuoles in
the cytoplasm.  Atrophy—decrease in the number or size of cells that can lead to
a decrease in organ size or tissue mass.
 Two processes, pinocytosis (the engulfment of fluids) and
phagocytosis (the engulfment and destruction of particles), are  Dysplasia—abnormal cytologic features and tissue organization;
forms of endocytosis. The vesicles formed by endocytosis either often is a premalignant change.
discharge their contents into the cellular cytoplasm or fuse with  Hyperplasia—increase in the number of cells in a tissue.
the organelles and the lysosomes.
 Hypertrophy—increase in the size of cells that can lead to an
 Phagocytosis is an important body defense mechanism increase in organ size.
 Metaplasia—change from one adult cell type to another (e.g.,
glandular to squamous metaplasia)
MEMBRANE FUNCTION:
ENDOCYTOSIS REACTIVE AND NEOPLASTIC
GROWTH PROCESS

 Polycythemia is the term used to refer to an increased concentration of


erythrocytes (erythrocytosis) in the circulating blood that is above normal
for gender and age. Secondary, or absolute, polycythemias reflect an
increase in erythropoietin production and should not be confused with
polycythemia vera or relative polycythemias
 Secondary polycythemia- produced by increased erythropoietin
production results from tissue hypoxia caused by such diverse factors as
defective high oxygen affi nity type of hemoglobin, certain types of
anemia, chronic lung disease, or inappropriate erythropoietin
production.
 Smoking is a common cause of secondary erythrocytosis.
ADAPTIVE CELL CHANGES  Neoplasm
 Familial polycythemia- an autosomal dominant trait that produces a
defect in the regulation of erythropoietin. A reduction in erythropoietin
production may also exist. In situations such as hypertransfusion, the
quantity of erythropoietin is reduced.
 Relative polycythemia- Increases in erythrocytes can result from
conditions that are not related to increased erythropoietin production.
(increased hct, decreased plasma)

DISORDERS OF ERYTHROPOIETIN

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 Blood volume: 7~8% (70-80ml/kg B.W)


 Plasma (60%) and cells (40%).

 Types of blood cells:


BLOOD PHYSIOLOGY  RBC (Erythrocytes), WBC (Leukocytes) and Platelets (Thrombocytes)

 Blood composition and properties  Main function:


 Blood cells  Maintain homeostasis
 Buffering pH
 Hematopoiesis
 Humoral regulation
 RBC: function, anemia.
 Body temperature regulation
 WBC
 Transportation:
 Platelet: function, coagulation and fibrinolysis.
 Gases, nutrients, hormones, and so on.
 Blood grouping and transfusion  Host defense:
 Immune reaction, coagulation.

Components and Characteristic

BLOOD COMPONENTS
Water: 93-95%  Water:
Plasma: 50-60%  93~95% (plasma); 65~68% (RBC); 81~86% (whole blood).
Solutes: 5-7% Proteins:  Solvent, humoral balance, osmotic pressure.

Nutrients  Electrolytes:
Whole Products  Na+, K+, Mg2+, Cl-, HCO3-, etc. Cell shape, pH.

blood Electrolytes:  Proteins:


 Albumin: 40-48g/L. Colloidal osmotic pressure; carrier;
Others: urea, gases.
buffer pH.
WBC, Platelet: 1%  Globulin: 15-30g/L. Immune reaction: antibody; carrier.
RBC: 40-50% (male)  Fibrinogen: 2-4g/L. Blood coagulation.

37-48% (female)

PHYSICAL AND CHEMICAL PROPERTIES

 Blood pH:
 Hemoglobin (Hb):
 Normal interval: 7.35~7.45.
 120-160g/L (male), 110-150g/L (female)
 Regulated by lung and kidney.
 Function: carry gases.
 Viscosity:
 Others:
 Friction of molecules and cells in blood.
 carbohydrates, lipids, amino acid, pigments,
hormones, gas (O2, CO2), and others like urea, uric  Relative viscosity:
acid.  Whole blood: 4~5 times to water (RBC).
 Plasma: 1.6~2.4 times to water (Proteins).
 Anemia or body fluid loss.

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 Osmotic pressure HEMOPOIESIS


 Definition:  The process of blood generation.
 An ability of a liquid to attract and retain water. It
drives osmosis. 300mmol/L
 Composition and roles: Cell Lineage Lifespan Daily Production Rate

 Crystal osmotic pressure: 298.7 mmol/L. RBC 120 days 2.5  109/L
Maintain shape and size of cells.
Neutrophil 7 hours 0.85  109/L
 Colloid osmotic pressure: 1.3 mmol/L.
Retain blood volume Platelet 10 days 2. 5  109/L

Decide distribution of water between


blood and interstitial fluid.

 Cell count and volume:


 Hematocrit: Percentage of blood volume occupied by packed  Volume:
cell volume.
 4.5~5.51012/L, average 5.01012/L (male).
 3.8~4.61012/L, average 4.21012/L (female).

 Physical properties
 Permeability:

 Deformation:

 Fragility and hemolysis:


 Isosmotic solution and lower osmotic solution
 Suspension stability:
 The erythrocytes are very stable in suspension.
 Cause: repelling force of same charge and bigger
surface area.

 Erythrocytes Sedimentation Rate (ESR):


Sedimentated distance of RBC after one hour.
HEMOGLOBIN (HB)
0~15 mm/h (male), 0~20 mm/h
(female).
 HB is made up of two
Ratio of Surface area/Volume of RBC. polypeptide  chains and 
chains.
Albumin, globulin, fibrinogen, and
cholesterol.  Each polypeptide has alpha
helical segments folded and
Rouleaux: RBC aggregate. bent into a globular
configuration, with a heme
 Function of RBC: ring within a pocket where the
iron molecule can interact
 The main constituent of RBC is hemoglobin. with oxygen.

 To deliver O2 to tissues by hemoglobin.

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 RBC Maturation factors:


 Hb formation materials:
 Vitamin B12:
 Protein: enough intake from food.
 Cobalamine, 2~5g/d.
 Iron: 3-4g/person. Mainly in Hb (70%).
 Produced by gut bacteria (esp. in ruminants). Good sources
 Degrading Hb: 95%. include meat, liver, fish, eggs and milk.
 Absorbed from small intestine: 1mg/d, 5%.  Absorbed in terminal ileum with intrinsic factor’ help.
 Microcytic hypochromic anemia: Lack of iron.  Function: Improve utilization of FA.
 Folic acid:
 FA is essential for the synthesis DNA.
 Synthesized by microorganisms and higher plants.
 Good sources are green leafy vegetables, yeast and organ
meats.
 Absorbed in the proximal jejunum.

 Lack of folic acid and vitb12: give rise to immature cells due to
DNA synthesis derangement.
•REGULATION OF ERYTHROPOIESIS:
 Megaloblast anemia.
HYPOXIA:  EPO RBC
Hemopoitic stem cell (uncommitted progenitor)

Erythrocytic progenitor (committed progenitor)
 EPO
Pronormblast (precursor)

Normoblast, Reticulocyte

Mature RBC (without nucleus)

 Erythropoietin (EPO): WHITE BLOOD CELLS (LEUCOCYTE)


A glycoprotein, 34kd. Produced in interstitial cells in cortical

 WBC:
kidney such as fibroblast, endothelial cells.
 4~10109/L, average is 7109/L.
 Roles:
 Include:
 Erythrocytic progenitor proliferate and differentiate to
precursor.  neutrophil, eosinophil, basophil
Accelerate precursor proliferation and differentiation.  monocyte, lymphocyte.

 Protection,
execute specific and non-specific
 Promote bone marrow release reticulocytes.
immune reaction.
 Renal type anemia: EPO production decrease
 Physical and chemical properties
 Other hormones:  Chemotaxis: attracted by chemical substances
 Androgen, thyroid hormone, parathyroid hormone,etc. released by bacteria and foreign substances.
 RBC destruction:  Movement: Move to chemotaxic source
 Phagocytosis: engulf and digest
 Life span of RBC is about 120 days. Older cells

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 Monocytes:
 15~30m, 0.12 ~ 0.8109/L, 3 ~ 8%.
 Neutrophil:  Monocytes-macrophages system:
 10~12m, 2.0~7.0109/L, 60-70%.  Monocytes (in blood) wander into tissues and become
macrophages (50 ~ 80 m). Stronger phagocytosis.
 Function:
 Contain many kinds of cytokines such as CSF, ILs, TNF, INF-
 Phagocytosis: older cells, becteria, dead tissues, and a,b.
other foreign substances.
 Roles:
 To execute non-specific immune activity in first front.
 Engulf and clear: bacteria, vermins, older, necrotic tissues,
dead neutrophils, dead cells and fragments.
 Activate lymphocytes to execute specific immune
COMPOSITION AND FUNCTIONS response.
 Recognize and kill cancer cells.
 Produce CSF, Ils, TNF, INF-, , regulate growth of
granulocytes.

 Lymphocytes:  Eosinophils
 0.8~4.0109/L, 20 ~ 40%.  0.02~0.5 109/L, 0.5~5%.
 Development of lymphocyte:  Functions:
 T lymphocyte:  Inhibit allergic reaction induced by basophils:
 lymphocytic stem cells  T lymphocytes (thymus gland).
Produce PGE to inhibit secretion of basophils;
 B lymphocyte:
Engulf substances secreted by basophils;
 lymphocytic stem cells  B lymphocytes (lymphoid tissue).

 Functions: Secrete matters to hydrolyze histamine and


5-HT.
 T lymphocytes: cellular type of immunity
 Phagocytic action to some worms.
 B lymphocytes: humoral immunity

PLATELET
 Hemostasis:
 Basophils  The process of blood clotting and then the subsequent
dissolution of the clot.
 0.0~1.0  109/L, 0~1%.
 Largecytoplastmic granules contain heparin, 5-
hydroxytryptamine and histamine. Platelet  activation  adhension  aggregation  clot  thrombus  FDP

 Function: fibrin plasmin


thrombin vWF ADP and TXA2
 Secrete heparin blood to prevent coagulation.
 Wander into tissue and become mast cell.
fibrinogen
 Induce allergy.
Blood Coagulation Fibrinolysis

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 Anatomic physiology of platelet:  Membrane:


 2~4 m, thickness 1m.  Receptor: For adhension, aggregation and coagulation.
 Phospholipid: provides the lipid cofactors needed for
coagulation reactions.
 Granules in platelet:
 -granules: coagulation factors, growth factors (e.g.
PDGF).
 -granules (dense bodies): Ca2+, ADP and serotonin.
 Volume: 100~300 109/L in adult.
 Thrombocytopenia: <50 109/L,  hemorrhage
 Thrombocytosis: >1000109/L,  Thrombosis

 Aggregation:
 Physical properties
 Activated platelets aggregate together.
 Adhesion:  Activation of platelets: induced by thrombin.
 Mediated by von Willebrand factor (vWF).  Thrombin + receptor  initiate signal cascade.
 vWF is producted and stored in a-granules of platelets. Also  G-protein, and phospholipase C(PLC-g).
synthesized by megakaryocytes.  PLC-g  IP3 and DAG formation.
 Function of vWF:  IP3  Ca2+ , and DAG  PKC.
 Toact as a bridge between glycoprotein on the surface of
platelets (GPIb/IX) and collagen fibrils.
 Serves as a carrier protein for factor VIII.
 Mechanisms:
 Ca2+  phospholipase A2 (PLA2) arachidonic acid  thromboxane
 von Willebrand Disease (vWD): deficiency in vWF a patient A2 (TXA2)
with long bleeding time, a low level of factor vWF/VIII
complex.  PKC ADP  fibrinogen to adhere to two platelet surface
glycoproteins (GPIIb and GPIIIa)  fibrinogen-induced platelet
 Bernard-Soulier Syndrome:deficiency of glycoprotein Ib/IX. aggregation.
 Glanzmann-Thrombasthenia, deficiency of glycoprotein IIb/IIIa.

 Contractile function:
 PLC-g  Ca2+  myosin light chain kinase (MLCK)
 MLCK  phosphorylation of light chain of myosin
 Myosin interacts with actin
 Platelet morphology, motility, and clot retraction.

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