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Blood
Chapter 17
Blood Composition
• Formed Elements = cells (~45%)
– Red Blood Cells (RBCs, Erythrocytes)
– White Blood Cells (WBCs, Leukocytes)
– Platelets
• Plasma = soluble materials (~55%)
Blood Composition
• Percentage of blood that is formed elements –
hematocrit
– Normal Values
Male 42-52% Female 37-47%
• Note: WBCs take up <1%, Plasma is majority (55%)
..Blood Composition
• Total Blood Volume
Male = 5-6 L
Female = 4-5 L
Plasma
• Straw-coloured fluid
– ~91-93% water, 7% proteins, 1.5 % other solutes
• Nutrients
– fats, carbohydrates (glucose), amino acids, minerals,
vitamins
• Wastes – by-products of living tissue metabolism
(creatinine, lactic acid, ammonia, CO2, etc.)
Plasma
• Plasma Proteins
– Albumin (54%) - osmosis and carriers
– Globulins (38%)- antibodies
– Fibrinogen (7%)- clotting
• Other:
– oxygen
– Electrolytes (Na, K, Ca, Cl, HCO3)
– hormones
Plasma Proteins
• Functions:
– Osmotic
• albumins pull water back into capillary by osmotic pressure
– Antibodies
• globulins act to recognize foreign material
– Buffers
• limit pH changes by taking up H+
• normal pH of blood: 7.35-7.45 (slightly alkaline)
– Lipid Transport
• Lipoproteins are complexes of fat and protein
• eg. LDL’s and HDL’s (High/Low Density Lipoproteins
RBCs
• Biconcave discs, anucleate, essentially no organelles
• Sickle cell – see next slide
• 5 million cells/mm3
• Normal Values
Male
4.5-6.5 x 1012 /L
Female
4.2-5.5 x 1012 /L
• Why do men have more?
• Does this match with hematocrit values?
•
Sickle
Cell
Anemia
Inherited condition – predominantly African gene pool
– cells lose the biconcave shape when in low oxygen (exercise
may deplete O2)
– becomes sickle shaped – get lodged in capillaries (often in
lungs) – painful and infections can start
– Survived genetic selection in Africa because SCA patients don’t
tend to suffer as badly from malaria
RBCs
• ~ 10,000 new cells are made every second to
replace 10,000 cells that have died in that
second
• Where do they get produced?
– red bone marrow
• Where are they destroyed?
– the spleen – recovers iron in heme, uses globin to
make amino acids
– recycling at its finest
RBCs
• Cells have no nuclei
• packed full of hemoglobin – almost 1/3 of the
volume
• Normal Values
Male
16  2 g/100 mL
Female 14  2 g/100 mL
• note: g/100 mL is sometimes said “gram percent”
RBCs
• All that hemoglobin (abbrev. Hb) is meant to carry oxygen
• Hypoxia – tissue is starved of O2 –
– if Hb does not have enough oxygen, then hypoxia
– lips and other tissues may appear blue = cyanotic
• When Hb combines with 4 molecules of O2, it’s called
Oxyhemoglobin
– Loads in lungs
– most oxygen in blood is carried this way with some in plasma
– most carbon dioxide is carried dissolved in plasma with some in Hb.
• What is Deoxyhemoglobin? Where is it formed?
• What is Carbaminohemoglobin? Where is it formed?
WBCs
• Formally called Leukocytes
– nucleated
– 8,000/mm3 (4 to 10 x 109 /L)
• (yes, that’s 4 to 10 billion per litre)
– if values fall below this – leukopenia (low WBC
count)
– if values are above this – leukocytosis (high WBC
count)
– Why would either occur?
WBCs
• To Major Groups of Leukocytes
– Granular
• granules clearly appear within the cytoplasm
• form ~70% of all leukoctyes
– Agranular – no such granules
• Wright’s stain – two dyes produce a neutral
stain
– Eosin (red) – acidic dye
– Methylene blue – basic dye
1.
Granular
WBCs
Neutrophils – 60% of total (most common)
–
pale lilac in stain (granules take up both
red and blue dyes – neutral)
–
nucleus often multi-lobed
•
•
Phagocytic – bacteria slayers
ameboid movement in tissues
–
•
get in tissues by diapedesis = “leaping across”
– move across capillary membranes into tissues
accumulate as pus around wounds
Granular
WBCs
Eosinophils – 3% of total
2.
–
–
–
deep red nucleus and lighter red granules attract
red dye (eosin)
nucleus looks like phone receiver (bilobed)
Increase in response to
•
•
parasitic worms – tapeworms, flukes, pinworms, hookworms)
allergies – may lessen response
Granular
WBCs
Basophils – 1% of total (rarest of all)
3.
–
–
–
granules stain purplish-black – the basic (methylene
blue) dyes
nucleus U or S shaped, with obvious constrictions
granules contain the Chemicals
•
•
•
Histamine – inflammatory response, promotes leaky capillaries
(edema), dilates blood vessels and attracts neutrophils
Heparin – anticoagulant
Function is very similar to Mast cells, though unrelated
Agranular
WBCs
Monocytes – 3-8% of total
1.
–
–
–
largest of all leukocytes (several times an RBC)
nucleus U or kidney shaped, with obvious constrictions
become macrophages
•
•
–
migrate to alveoli in lung, connective tissue beneath skin, liver
(fixed in place – called Kupffer cells), lymph nodes
destroy bacteria cells and viruses by phagocytosis – even some
cancer cells
did you know….
•
a Kupffer cell can destroy a bacterium in < 1/100 seconds?
Agranular WBCs
Lymphocytes – 25-33% of total (2nd most common)
2.
–
–
–
nucleus stains dark-purple, fills most of cell
most often found in lymph nodes, spleen
important in immune response to disease
•
T cells
–
–
•
B cells
–
–
–
mature in bone marrow
produce antibodies to recognize foreign material
Lymphoblasts
•
•
mature in the Thymus gland
act against virus-infected cells and tumour cells
produce new lymphocytes and monocytes
so, did you notice the three platelets?
Platelets
• Thrombocytes (Platelets)
– megakaryocyte fragments = platelets
“large nucleus cells”  cell fragments
– (not really cells at all) – only ¼ size of lymphocytes
– only 400,00/mm3 (140-440 x 109/L)
– Note: serum is plasma without platelets  won’t
clot
•
Hemostasis
Hemostasis = “blood halting”
– the formation of a blood clot
– loss of blood is stopped when vessels rupture – usually takes
only 3-6 minutes
– Overview:
3 stages
• vascular spasm
– dramatic vasoconstriction  slow blood flow  reduce losses
• platelet plug formation - platelets ‘stick’ (adhere) to the wound
(collagen fibres) and each other, creating a plug
– platelets enhance vascular spasm - serotonin
– platelets attract other platelets - ADP
• coagulation
– cascade of reactions  blood transforms into a gel
– results are due to a fibrinogen mesh that traps blood cells and seals the
hole
Hemostasis
• Platelets don’t stick to normal (undamaged)
endothelium (lining of b.v.’s) or to each other
– why?
– negative charge of healthy tissue repels them
(platelets are also negatively charged)
– Damaged tissue loses its negative charge
 platelets adhere to wounds in b.v. (exposed collagen
fibres)
– the Platelet Plug is formed, reducing loss of blood
– Plasmin
Hemostasis
• as the wound heals, clot is dissolved
• plasmin does this – starts within 2 days of clot
formation
• dissolves fibrin of clot
– Purpura
• small reddish or purple spots on skin - petechiae
• sub-q bleeding from small vessels
• results from insufficient platelet count
(thrombocytopenia)
– Serotonin
• released by platelets
• enhances vasoconstriction  reduces blood loss
Clotting
• Two pathways of clot formation
– Intrinsic – “found within”
• Blood can clot on it’s own in a tube with no external stimulus
– Extrinsic – “found without”
• Blood clots in response to stimuli from outside eg. chemicals released
from damaged cells/tissues
• shorter (quicker) path bypasses many steps of intrinsic path
– Notes:
• There are over 30 substances involved
• Many (the “Factors”) are numbered I to XIII
» the numbering is NOT in the sequence in which the reaction proceeds
• Calcium is ABSOLUTELY essential for clot formation
• the main difference between extrinsic and intrinsic pathways is:
– extrinsic is a shorter path because of the use of Tissue thromboplastin
• all other steps past that stage are shared in common
Clotting
• Extrinsic Pathway to a Clot
– fastest of the two pathways (shortcut)
– Tissue Thromboplastin
“thrombo” = clot
“plastic” = to form
• aka Tissue Factor (TF) - produced by damaged cells
• becomes Factor X (needs Ca2+)
– Factor X
• which becomes Prothrombin activator (needs Ca2+)
– Prothrombin activator
• converts Prothrombin (plasma protein) into Thrombin
(enzyme) (needs Ca2+)
•
Clotting
Extrinsic Pathway to a Clot (cont’d.)
– Thrombin causes fibrinogen (plasma protein - soluble) to
polymerize (join together) into long fibrin strands (insoluble)
– Thrombin also activates factor XIII
• factor XIII + Ca2+ causes fibrin strands to cross-link forming a web or
mesh
– Fibrin mesh traps formed elements (platelets, blood cells and
fibres) in blood
• creates a clot that seals the wound over  3-6 minutes after injury
Clotting
Extrinsic
Clotting
• Intrinsic Pathway to a Clot
• longer pathway
– provoked by
•
•
•
•
plaques that become rough
lining damaged by inflammation
rupture of minor vessels
platelets adhere to collagen fibres exposed and to themselves
– Hageman Factor (Factor XII)
• becomes activated by collagen fibres (needs Ca2+)
• a cascade through four (4) Factors (needs Ca2+) to become
– Factor X
• which becomes Prothrombin activator (needs Ca2+)
– The rest is the same as for the extrinsic pathway …
Intrinsic
Helpers along the way
• Vitamin K
– used indirectly – required by liver to make many of the
clotting Factors
• Plasma proteins
– fibrinogen is converted to fibrin
– prothrombin is converted to thrombin
– plasmin will dissolve clots
• Anticoagulant
– prevents clotting eg. heparin (from basophils and mast
cells)
More on Clottin
•
Thrombosis
– formation of a clot
– causes include
1.
2.
3.
4.
•
injury to b.v.
congestion (slow blood flow)
polycythemia (viscous blood due to  RBC’s
hypercoagulability – smoking or high fat diet
promotes platelet adherence
Embolis
– a mobile clot
What can you do?
•
To hasten the formation of a clot
a)
b)
c)
d)
e)
apply gauze (surface for platelets to adhere)
apply heat
sutures
apply fibrin
apply thrombin