Physiology of Blood
Terms
undefined, object
copy deck
- blood clot/gas bubble floating in blood
- embolus
- factors interfere with normal clotting
-
1. prothrombin III - deactivates thrombin
2. protein C - inhibits clotting Factors
3. heparin - inhibits thrombin; prevents adherence of platelets to injured site - undesirable clotting
- Thromboembolytic Disorders
- blood clot in normal blood vessel
- thrombus
- can dissolve a clot
- TPA, streptokinase
- inhibits Thromboxane formation
- aspirin
- inhibits thrombin & platelet deposit
- heparin
- anticoagulant, blocks Vitamin K
- dicumarol
- reduced platelet count; generally below 50,000 per cubic millimeter; can cause excessive bleeding from vascular injury
- thrombocytopenia
- impaired liver function - lack of (Clotting Factors) that are made in liver
- procoagulants
- essential for liver to make Clotting Factors for coagulation
- vitamin K
- hereditary bleeding disorders that occur almost exclusively in males
- hemophilias
-
hemophilias
defective Factor VIII (83%) - hemophilia A
-
hemophilias
defective Factor IX (10%) - hemophilia B
-
hemophilias
now produces genetically engineered TPA and Factor VIII; patients do not need transfusions as often - Genentech. Inc.
- all cells and plasma; anticoagulants (citrate and oxalate salts) used
- whole blood transfusion
- most of the plasma has been removed prior to transfusion
- packed red blood cells
- glycoproteins on the surface of blood cells; causes "agglutination" (clumping)
- agglutinogens
- determined by presence or absence of Type A and Type B agglutinogen proteins on cell membrane
- ABO Blood Groups
- NO Rh factor
- Rh negative (Rh-)
- an Rh factor is present
- Rh positive (Rh+)
- type A blood
-
GENES: A/A, A/O, O/A
PEOPLE: (30-40%)
Antibodies: Anti-B
Receive Blood from: A, O - type B blood
-
GENES: B/B, B/O, O/B PEOPLE: (l0-30%)
Antibodies: Anti-A
Receive Blood from: B,O - type AB blood
-
GENES: A/B or B/A PEOPLE: (3-5%)
Antibodies: none
Receive Blood from: A, B, AB, O - type O blood
-
GENES: no A or B PEOPLE: (40-50%)
Antibodies: Anti-A, Anti-B
Receive Blood from: O only -
Diagnostic Blood Tests
blood glucose level - diabetes
-
antibodies against either A or B agglutinogen (whichever is not present)
a. transfusion reaction - patient's antibodies attack the donor blood - agglutinins
- transfusion reaction - patient's antibodies attack the donor blood
-
A (anti-B) receives A,O (not B)
B (anti-A) receives B,O (not A)
AB (none) receives A, B,AB,O (universal recipient)
O (anti-A,anti-B) receives O
(universal donor) - antibodies against either A or B agglutinogen (whichever is not present)
- agglutinins
- when incorrect blood transfused, antibodies will "clump" new blood
- agglutination
- after clumping, RBCs may rupture, releasing hemoglobin, harming kidney
- hemolysis
- hemolysis, treatment for:
- dilute hemoglobin, administer diuretics
- a different group of agglutinogens
- Rh factor
- delayed and less severe than in ABO confrontation
- transfusion reaction
- directly from the mother (Rh-) to the newborn (Rh+)
- exchange transfusion
- Rh- mother antibodies attack Rh+ of older newborn; results in anemia and low oxygen levels (hypoxia)
- erythroblastosis fetalis
-
Diagnostic Blood Tests
lipidemia - high in fat; yellowish plasma
- serum with anti-Rh agglutinins which will clump the Rh factor, blocking the reaction of motherÂ’s antibodies
- RhoGAM
- mixing Donors Blood with Recipient Antibodies (Anti-A, Anti-B, anti-Rh) in order to identify agglutination
- Blood Typing
-
Diagnostic Blood Tests
generally higher WBC count - infection
-
Diagnostic Blood Tests
significantly higher WBC count - leukemia
- Ways of Expanding Blood Volume to Avoid Shock
-
1. pure plasma without antibodies
2. plasma expanders - purified human serum albumin, plasminate, dextran
3. isotonic saline - normal electrolyte solution isotonic to blood plasma (Ringer's Solution) -
Diagnostic Blood Tests
anemia - low hematocrit (below 35%)
-
Diagnostic Blood Tests
counts % of each of the different leukocytes (helps diagnose) - differential WBC count
-
Diagnostic Blood Tests
time for clotting to occur - prothrombin time
-
Diagnostic Blood Tests
diagnose thrombocytopenia - platelet count
-
Diagnostic Blood Tests
overall blood review - complete blood count
-
Factors Limiting Growth and Formation of Clots
Limiting Normal Clot Growth -
a. blood moves too fast to allow procoagulants
b. factors interfere with normal clotting -
Clot Eradication (Fibrinolysis)
healing occurs over ? days - healing occurs over 2 - 10 days
-
Clot Eradication (Fibrinolysis)
causes the activation of plasminogen - tissue plasminogen activator (TPA)
-
Clot Eradication (Fibrinolysis)
plasminogen--> ? - plasmin
-
Clot Eradication (Fibrinolysis)
? degrades proteins within the clot - plasmin
- the actual cellular components of blood (special connective tissue)
-
formed elements
erythrocytes
leukocytes
platelets - complex non-cellular fluid surrounding formed elements; protein & electrolytes
- blood plasma
-
Separation of Components in a Centrifuge
VOLUME LAYER
55% top - clear/yellowish PLASMA
-
Separation of Components in a Centrifuge
VOLUME LAYER
<1% middle -
thin/whitish buffy coat
with LEUKOCYTES & PLATELETS -
Separation of Components in a Centrifuge
VOLUME LAYER
45% bottom - reddish mass - ERYTHROCYTES
- red blood cells
- erythrocytes
- white blood cells
- leukocytes
- cell fragments for clotting
- platelets
- percentage by VOLUME of erythrocytes when blood is centrifuged (normal = 45%)
- hematocrit
-
Characteristics of Blood
bright red - oxygenated
-
Characteristics of Blood
dark red/purplish - unoxygenated
- Characteristics of Blood
-
1. much more dense than pure water
2. pH range from 7.35 to 7.45 (slightly alkaline)
3. slightly warmer than body temperature 100.4 F
4. typical volume in adult male 5-6 liters
5. typical volume in adult female 4-5 liters
6. typically 8% of body weight - Distribution & Transport
-
a. oxygen from lungs to body cells
b. carbon dioxide from body cells to lungs
c. nutrients from GI tract to body cells
d. nitrogenous wastes from body cells to kidneys -
Regulation (maintenance of homeostasis)
maintenance of normal body pH - blood proteins (albumin) & bicarbonate
-
Regulation (maintenance of homeostasis)
maintenance of circulatory/interstitial fluid - electrolytes aid blood proteins (albumin)
- Regulation (maintenance of homeostasis)
- maintenance of temperature (blushed skin)
-
Protection
"seal" vessel damage - platelets and proteins
-
Protection
leukocytes, antibodies, complement proteins - protection from foreign material & infections
-
Erythrocytes (red blood ells; RBCs)
Structure
diameter / thickness - 7.5 micron diameter; 2.0 micron thick
-
Erythrocytes (red blood ells; RBCs)
Structure
ideal for gas exchange - biconcave disk shape
-
Erythrocytes (red blood ells; RBCs)
Structure
elastic protein; allows shape change - spectrin
-
Erythrocytes (red blood ells; RBCs)
Structure
anucleate (no nucleus) - mature cells
-
Erythrocytes (red blood ells; RBCs)
Structure
very few organelles; mainly a hemoglobin carrier - hemoglobin – 33% of cell mass; carries oxygen
-
Erythrocytes (red blood ells; RBCs)
Structure
only anaerobic respiration - no mitochondria
-
Erythrocytes (red blood ells; RBCs)
Structure
ratio erythrocytes:leukocytes - 800:1
-
Erythrocytes (red blood ells; RBCs)
Structure
red blood cell count: # cells per cubic millimeter
i. normal male count - 5.1 to 5.8 million
-
Erythrocytes (red blood ells; RBCs)
Structure
red blood cell count: # cells per cubic millimeter
i. normal female count - 4.3 to 5.2 million
- large molecules with globin and hemes
- hemoglobin
- complex protein with 4 polypeptides (2 alpha and 2 beta polypeptides)
- globin
- IRON containing pigment part of hemoglobin to which oxygen binds
- heme group
- each polypeptide has
- one heme group
- each heme carries
- one O2
-
normal hemoglobin levels (grams/l00 ml blood)
infants - 14-20 grams/l00 ml
-
normal hemoglobin levels (grams/l00 ml blood)
adult female - 12-16 grams/100 ml
-
normal hemoglobin levels (grams/l00 ml blood)
adult male - 13-18 grams/l00 ml
- when oxygen is bound to IRON
- oxyhemoglobin
- no oxygen bound to IRON
- deoxyhemoglobin
- when carbon dioxide bound (to polypeptide chain)
- carbaminohemoglobin
- the maturation, development and formation of blood cells
- hematopoiesis (hemopoiesis)
- location of hematopoiesis; in blood sinusoids which connect with capillaries; mainly in axial skeleton and heads of femur & humerous
- red bone marrow (myeloid tissue)
- the mitotic precursor to blood cells before differentiation
- hemocytoblast (stem cell)
- maturing cell becomes "committed" to being certain type blood cell
- differentiation
- the maturation, development, and formation of Red Blood Cells (erythrocytes)
- erythropoiesis
- erythropoiesis
-
hemocytoblast ->
proerythroblast ->
early (basophilic) erythroblast ->
late (polychromatophilic) erythroblast->
(hemoglobin) normoblast ->
(nucleus ejected when enough hemoglobin)
reticulocyte ->
(retaining some endoplasmic reticulum)
ERYTHROCYTE - 3-5 DAYS
- hemocytoblast -> reticulocyte
- 2 DAYS (in blood)
- reticulocyte -> ERYTHROCYTE
- 100-120 DAYS
- ERYTHROCYTE lifespan
- ERYTHROCYTE death
- (primarily destroyed by macrophages in the spleen)
-
Regulation of Erythropoiesis
hormonal controls
hormone that stimulates RBC production - erythropoietin
-
Regulation of Erythropoiesis
hormonal controls
DECREASED oxygen level in blood causes - KIDNEYS to increase release of erythropoietin
-
DECREASED oxygen level in blood
causes -
1. Less RBCs from bleeding
2. Less RBCs from excess RBC destruction
3. Low oxygen levels (high altitude, illness)
4. Increased oxygen demand (exercise) - Eythropoietin now genetically engineered and synthesized by
- AMGEN of Thousand Oaks
- Testosterone can also mildly stimulate production of
- RBCs in humans
- essential for hemoglobin to carry oxygen
- Iron
- 65% of Fe in body is in
- hemoglobin
- liver and spleen store most excess Fe bound to
- ferritin and hemosiderin
- Fe in blood bound to
- transferrin
- daily Fe loss:
- 0.9 mg men/l.7 mg women
- women also lose Fe during
- menstrual flow
- essential for DNA synthesis in early mitotic divisions leading to erythrocytes
- B-complex Vitamins - Vitamin B12 and Folic Acid
- a symptom that results when blood has lower than normal ability to carry oxygen
- Anemias
- loss of blood from bleeding (wound, ulcer, etc.)
- hemorrhagic anemia
- erythrocytes rupture (hemoglobin/transfusion problems, infection)
- hemolytic anemia
- red marrow problems (cancer treatment, marrow disease, etc.)
- aplastic anemia
-
Decrease in Hemoglobin
low Iron levels (diet; absorption, bleeding, etc.) - iron-deficiency anemia
-
Decrease in Hemoglobin
low Vitamin B12 (diet, intrinsic factor for Vit B absorption) - pernicious anemia
-
Abnormal Hemoglobin (usually genetic)
easily ruptured RBCs (Greek & Italian genetic link) - thalassemia
-
Abnormal Hemoglobin (usually genetic)
sickle-shaped RBCs (genetic Africa, Asia, southem Europe link) - sickle-cell anemia
- excess RBC count, causes thick blood
- Polycythemia
- bone marrow problem; hematocrit may jump to 80%
- polycythemia vera
- high altitude (normal); or too much erythropoietin release
- secondary polycythemia
- RBCs previously withdrawn are transfused before an event; more RBCs, more oxygen delivery to the body
- blood doping in athletes
-
Leukocytes (white blood cells; WBCs)
General Structure and Function
protection from - microbes, parasites, toxins, cancer
-
Leukocytes (white blood cells; WBCs)
General Structure and Function
?% of blood volume; ? per cubic mm blood - 1% of blood volume; 4-11,000 per cubic mm blood
-
Leukocytes (white blood cells; WBCs)
General Structure and Function
can "slip between" capillary wall - diapedesis
-
Leukocytes (white blood cells; WBCs)
General Structure and Function
movement through the body - amoeboid motion
-
Leukocytes (white blood cells; WBCs)
General Structure and Function
moving in direction of a chemical - chemotaxis
-
Leukocytes (white blood cells; WBCs)
General Structure and Function
increased "white blood cell count" in response to bacterial/viral infection - leukocytosis
-
Leukocytes (white blood cells; WBCs)
General Structure and Function
contain membrane-bound granules (neutrophils, eosinophils, basophils) - granulocytes
-
Leukocytes (white blood cells; WBCs)
General Structure and Function
NO membrane-bound granules (lymphocytes, monocytes) - agranulocytes
- granules in cytoplasm can be stained with Wright's Stain; bilobar nuclei; 10-14 micron diameter; all are phagocytic cells (engulf material)
- Granulocytes
- destroy and ingest bacteria & fungi (polymorphonuclear leuks.; "polys")
- neutrophils
-
a. most numerous WBC
b. basophilic (blue) & acidophilic (red)
c. defensins - antibiotic-like proteins (granules)
d. polymorphonuclear - many-lobed nuclei
e. causes lysis of infecting bacteria/fungi
f. HIGH poly count --> - neutrophils
- lead attack against parasitic worms
- eosinophils
-
a. only 1-4% of all leukocytes
b. two-lobed, purplish nucleus
c. acidophilic (red) granules with digest enzymes
d. phagocytose antigens & antigen / antibody complex
e. inactivate chemicals released during allergies - eosinophils
- releases Histamine which causes inflammation, vasodilation, attraction of WBCs
- basophils
-
a. RAREST of all leukocytes (0.5%)
b. deep purple U or S shaped nucleus
c. basophilic (blue) granules with HISTAMINE
d. related to "mast cells" of connective tissue
e. BOTH release Histamine with "IgE" signal
- basophils
- WBCs without granules in cytoplasm
- C. Agranulocytes
- (thymus) respond against virus infected cells and tumor cells
- T lymphocytes
- (bone) differentiate into different "plasma cells" which each produce antibodies against different antigens
- B lymphocytes
- lymphocytes primarily in
- lymphoid tissues
- lymphocytes nucleus
- very large basophilic (purple) nucleus
- small lymphocytes in blood ? microns
- 5-8 microns
-
larger lymphocytes in lymph organs
? microns - 10-17 microns
- differentiate to become macrophages; serious appetites for infectious microbes
- monocytes
-
largest of all lymphocytes (18 microns)
dark purple, kidney shaped nucleus - monocytes
- the production, differentiation, and development of white blood cells
- leukopoiesis
- hematopoietic hormones that promote leukopoiesis
- colony stimulating factors (CSF)
- M-CSF
-
macrophage-monocyte CSF
(colony stimulating factors) - G-CSF
- granulocyte CSF
- GM-CSF
- granulocyte-macrophage CSF
- multi CSF
- multiple lymphocyte action
- IL-3
- interleukin 3 (general lymphocytes)
- all cells derived from hemocytoblast
- leukopoiesis
-
EOSINOPHIL
NEUTROPHIL
BASOPHIL
lifespan? - 0.5 to 9 day lifespan
- abnormally low WBC count
- leukopenia
-
leukopenia
causes - HIV infection, glucocorticoids, chemotherapy
- cancerous condition of "line" of WBCs
- leukemia
- myelocytic leukemia
- myelocytes
- lymphocytic leukemia
- lymphocytes
- acute leukemia
- cancer spreads rapidly
- chronic leukemia
- cancer progresses slowly
- caused by Epstein-Barr virus, excessive monocytes and lymphocytes; fatigue, sore throat, fever; 3 week course
- infectious mononucleosis
- thrombocytes - "clotting"
- Platelets
-
Platelets (thrombocytes - "clotting")
size? - very small, 2-4 microns in diameter
-
Platelets (thrombocytes - "clotting")
approximately ? per cubic millimeter - approximately 250-500,000 per cubic millimeter
-
Platelets (thrombocytes - "clotting")
essential for ? of damaged vasculature - essential for clotting of damaged vasculature
- regulates platelet production
- thrombopoietin
-
hemocytoblast->
myeloid stem cell->
megakaryoblast->
promegakaryocyte->
megakaryocyte-> (large multilobed nucleus)
platelets (anucleated parts of megakaryocyte cytoplasm) - Formation of Platelets
- plasma makes up ?% of normal blood by volume
- plasma makes up 55% of normal blood by volume
- water is ?% of the plasma by volume
- water is 90% of the plasma by volume
- different SOLUTES in the plasma
-
albumin
globulins
clotting proteins
other proteins
nutrients
electrolytes - pH buffer & osmotic pressure
- albumin
- binding proteins & antibodies
- globulins
- clotting proteins
- prothrombin & fibrinogen
- other proteins
- enzymes, hormones, others
- glucose, fatty acids, amino acids, cholesterol, vitamins
- nutrients
- Na+, K+, Ca++, Mg++, Cl-, phosphate, sulfate, bicarbonate, others
- electrolytes
- stoppage of blood flow after damage
- Hemostasis
-
Hemostasis
General Characteristics -
1. vascular spasms (vasoconstriction at injured site)
2. platelet plug formation (plugging the hole)
3. coagulation (blood clotting - complex mechanism) - first response to vascular injury
- Vascular Spasms / VASOCONSTRICTION
- VASOCONSTRICTION is stimulated by:
-
a. compression of vessel by escaping blood
b. injury "chemicals" released by injured cells
c. reflexes from adjacent pain receptors - Formation of a Platelet Plug
-
1. damage to endothelium of vessel
2. platelets become spiky and sticky in response
3. platelets attach to damaged vessel wall to plug it
4. platelets produce thromboxane A2 - granule release
5. serotonin release enhances vascular spasm
6. ADP - attracts and stimulates platelets at site
7. prostacylin - inhibits aggregation at other sites - Coagulation
- blood clotting
- General Events in Clotting
-
platelet cells activated by damage->
PF3 and/or Tissue Factor produced by platelet cells->
Factor X activated->
prothrombin activator (enzyme)produced->
prothrombin conversion -> thrombin (another enzyme)
thrombin stimulates: fibrinogen----> fibrin mesh - chemical that inhibits clotting
- anticoagulant
- chemical that promotes clotting
- procoagulant
- pathway - within the damaged vessel
- intrinsic pathway
-
a. more procoagulants needed (I-XIII) toward PF3 and Factor X
b. allows more "scrutiny" before clotting occurs - intrinsic pathway
- pathway in outer tissues around vessel
- extrinsic pathway
- skips intrinsic steps straight to PF3 and Factor X
- tissue thromboplastin (Tissue Factor)
-
a. tissue thromboplastin (Tissue Factor) - skips intrinsic steps straight to PF3 and Fac X
b. allows rapid response to bleeding out of vessel (clot can form in 10 to 15 seconds) - extrinsic pathway - in outer tissues around vessel
- After activation of Factor X, common pathway:
-
Factor X, PF3 (thromboplastin), Factor V, Ca++ -->
prothrombin activator ->
prothrombin converted ->
thrombin (active enzyme)
thrombin stimulates: fibrinogen -> fibrin (meshwork)
Ca++ & thrombin -> Factor XIII (fibrin stabilizer) - shrinking of clot
- Clot Retraction
-
Clot Retraction (shrinking of clot)
causes contraction of platelets - actomyosin
-
Clot Retraction (shrinking of clot)
plasma WITHOUT clotting Factors - blood serum - plasma WITHOUT clotting Factors
-
Clot Retraction (shrinking of clot)
stimulates fibroblast migration and endothelial growth - platelet-derived growth factor (PDGF)
- Clot Eradication
- Fibrinolysis
-
1. anemia, fever, weight loss, bone pain
2. death from internal hemorrhage or infection
3. chemotherapy & radiation therapy used to treat - leukemia