TOO MUCH TIME - Find People
Transcript of TOO MUCH TIME - Find People
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Cell
O2
CO2
Nutrients
Waste
O2 / Energy
CO2 / Waste
CO2 / Waste
External environment:
O2 / Nutrients
Source
Sink
TOO MUCH
TIME
Transport System of the Body:
100 m 1 s
1 mm 100 s
1 cm 10000 s distance = time2
Cell
O2
CO2
Nutrients
Waste
O2 / Energy
CO2 / Waste
CO2 / Waste
External environment:
O2 / Nutrients
Transport System of the Body:
Source
Sink
Diffusion
Bulk flow
(pressure)
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Cardiovascular System:
Blood
• Only fluid tissue in body (connective tissue)
• pH = 7.35 – 7.45 (slightly alkaline)
• Temp. slightly higher than body temp. (38°C / 100.4°F)
• ~ 8% body weight (♂ = 5-6 L; ♀ = 4-5 L)
Function (“River of Life”):
Cardiovascular System – Blood
1) Distribution
• Delivers oxygen / nutrients
• Carries away metabolic wastes
• Transports hormones
2) Regulation
• Maintains body temperature / pH
• Maintains fluid volumes
3) Protection
• Prevents blood loss (e.g., clot formation)
Blood:
Bloodletting a
common medical
treatment in the
Middle Ages
• Prevents infection (e.g., antibodies)
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Erythrocytes
(~ 45%)
• Erythrocytes (RBC’s)
Buffy Coat
(~ 1%)
• Leukocytes (WBC’s)
• Platelets
Formed
elements
1) Formed Elements (living cells)
Plasma
2) Plasma
• Non-cellular fluid matrix (dissolved proteins)
Hematocrit:
% of whole blood containing
formed elements
Males ~ 47%
Females ~ 42%
Cardiovascular System – Blood
Blood Components:
A) Plasma
• Distributes materials / heat
Serum:
Plasma minus
clotting proteins
C) Other solutes (~ 2%; >100 different solutes present; Table 17.1)
Blood Components:
Cardiovascular System – Blood
Composition:
A) Water (~ 90%)
B) Protein (~ 8%)
(Primarily produced
by liver)
Albumin
• Osmotic pressure
• Transport
Globulins
• Transport ( / )
• Antibodies ()
Fibrinogen
• Clotting protein
• Electrolytes (e.g., sodium)
• Respiratory gases (e.g., O2)
(precisely maintained)
60% 36% 4%
• Organic nutrients (e.g., glucose)
• Nitrogenous waste (e.g., urea)
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Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figures 17.3 / 17.14
• Small (~ 7 m); biconcave (“certs”)
Heme (O2-binding pigment w/ iron) + Globin (protein)
4 globins / hemoglobin
(2 chains; 2 chains)
= 4 molecules O2
B) Erythrocytes (red blood cells – RBCs)
Blood Components:
Cardiovascular System – Blood
Shape maintained by network
of proteins (e.g., spectrin)
• Contain hemoglobin (O2 / CO2 transport protein)
Why maintain hemoglobin
in erythrocytes?
1) Leakage through capillary walls
• Anucleate (lacking nucleus); few organelles
2) Viscosity / osmotic pressure issues
250 million / cell
Structure complements function
1) Small size and shape equates to large
surface area / volume
Rapid respiratory gas loading / unloading
2) 97% of cell volume is hemoglobin (~ 250 million hemoglobin)
Mass transport of respiratory gases
3) Lack mitochondria (don’t burn oxygen)
Efficient transport of respiratory gases
B) Erythrocytes (red blood cells – RBCs)
Blood Components:
Cardiovascular System – Blood
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Erythropoiesis (red blood cell formation):
• ~ 2 million RBCs produced per second
• Formation occurs in red bone marrow
Sternum
Vertebra
Ribs
Axial skeleton
Age (years)
Low
High
Young Old
Femur
Tibia
Long bones
B) Erythrocytes (red blood cells – RBCs)
Blood Components:
Cardiovascular System – Blood
Hemocytoblast (stem cell)
Myeloid stem cell Erythroblast
(ribosome factory)
Normoblast
(nucleus
ejected)
Reticulocyte
(enters blood stream)
Erythrocyte
Erythropoiesis (red blood cell formation):
B) Erythrocytes (red blood cells – RBCs)
Blood Components:
Cardiovascular System – Blood
1 – 2 % of RBCs
Reticulocyte Count:
Provide rough index of RBC
formation rate
Entire process takes
~ 15 days
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Produced by the kidney
and liver
(~ 85%) (~ 15%)
Normal Blood Oxygen Level
Hypoxia
1) RBC loss
2) hemoglobin
3) Low O2
Reduced O2
level in blood
Kidney releases
erythropoietin
Erythropoietin stimulates
bone marrow
RBCs mature
more rapidly
Increased O2
level in blood
(-)
Erythropoiesis (red blood cell formation):
B) Erythrocytes (red blood cells – RBCs)
Blood Components:
Cardiovascular System – Blood
• Regulated hormonally by erythropoietin
B) Erythrocytes (red blood cells – RBCs)
Blood Components:
Cardiovascular System – Blood
• Dietary requirements must be met for normal RBC formation
Iron: (hemoglobin synthesis)
Vitamin B12 and folic acid
necessary for proper DNA synthesis
• Stored in liver & spleen in protein-iron
complexes ferritin and hemosiderin
Ferritin (24 protein subunits)
• Transported in blood bound to transferrin
Transferrin (Glycoprotein; 2 binding sites)
Erythropoiesis (red blood cell formation):
Free iron ions toxic!
• Acts as a catalyst for
the formation of
free radicals
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B) Erythrocytes (red blood cells – RBCs)
Blood Components:
Cardiovascular System – Blood
Destruction of Erythrocytes
• “Old” RBCs engulfed by macrophages
in spleen / liver
• Lose flexibility
Jaundice:
Yellowing of skin due to
bilirubin deposition
• Iron salvages; stored for re-use
• Heme group degraded to bilirubin
Bilirubin (captured by liver;
released via gallbladder) (yellow pigment)
Urobilinogen (metabolized in
large Intestine)
Stercobilin (brown pigment) (exits in feces)
• Globins recycled to amino acids
Pathophysiology:
Anemia ( oxygen carrying capacity of blood)
B) Erythrocytes (red blood cells – RBCs)
Blood Components:
Cardiovascular System – Blood
Decreased
number of RBCs
Decreased
hemoglobin content
Abnormal
hemoglobin
Hemorrhagic anemia
(blood loss)
Hemolytic anemia
(RBC rupture)
Aplastic anemia
(red marrow destruction)
Iron-deficiency anemia
(inadequate intake of iron)
Pernicious anemia
(deficiency of vitamin B12)
Microcytes
Macrocytes
Sickle-cell anemia
(genetic mutation – abnormal globin) Thalassemias
(genetic mutation – missing globin)
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Pathophysiology:
Polycythemia ( red blood cell number)
B) Erythrocytes (red blood cells – RBCs)
Blood Components:
Cardiovascular System – Blood
EPO Whole blood
Polycythemia increases blood viscosity,
causing it to flow sluggishly
Polycythemia vera
(bone marrow cancer)
Secondary polycythemia
(high altitude living)
Artificial polycythemia
(blood doping)
C) Leukocytes (white blood cells – WBCs)
Blood Components:
Cardiovascular System – Blood
• Only complete cell in blood (e.g., nucleus / organelles)
• ONLY utilize blood for transport
• Function in defense against disease ~ 4800 – 10,800 WBCs / l
Carman, C.V., Journal of Cell Science. 2009;122:3025-3035
Rolling
Inflamed endothelial cells sprout
cell-adhesion molecules (CAMs)
Margination Migration
Tight
adherence
Diapedesis
“leaping across”
Amoeboid
movement
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C) Leukocytes (white blood cells – WBCs)
Blood Components:
Cardiovascular System – Blood
Categories of Leukocytes:
1) Neutrophils (50 – 70%)
• Multi-lobed nucleus
• Engulfs bacteria / fungi
• Small granules
(hydrolytic enzymes/defensins)
Granulocytes (contain granules)
2) Eosinophils (2 – 4%)
• Bi-lobed nucleus
• Kills parasitic worms
• Large granules
(lysosomes)
3) Basophils (< 1%)
• Large granules
(histamines)
• U-shaped nucleus
• Vasodilator / attracts WBCs
Lifespan = hours – days
C) Leukocytes (white blood cells – WBCs)
Blood Components:
Cardiovascular System – Blood
Categories of Leukocytes:
1) Lymphocytes (15 – 45%)
T lymphocytes
B lymphocytes
• Large nucleus (spherical)
• Function in immunity
Agranulocytes (lack granules)
2) Monocytes (3 – 8%)
• U-shaped nucleus
• Largest of WBCs
• Function as macrophages
(differentiate in tissues)
Lifespan = hours – decades Lifespan = hours – months
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C) Leukocytes (white blood cells – WBCs)
Blood Components:
Cardiovascular System – Blood
Leukopoiesis (white blood cell formation):
Eosinophilic
myelocyte Eosinophilic
band cell
Hemocytoblast (stem cell)
Myeloid
stem cell
Lymphoid
stem cell
Myeloblast
Neutrophil
Neutrophilic
myelocyte
Basophil
Eosinophil
Neutrophilic
band cell
Basophilic
myelocyte Basophilic
band cell
Granules appear Nuclei arc
Lymphoblast Lymphocyte
Monoblast Monocyte
Hormones:
Interleukins
Colony-stimulating factors
(+)
migrate to
lymphoid tissue
Blood Components:
Cardiovascular System – Blood
C) Leukocytes (white blood cells – WBCs)
Pathophysiology:
Leukemia:
• Uncontrolled proliferation of WBCs (cancerous)
• Named according to abnormal
cell line involved
Lymphocytic leukemia
Myelocytic leukemia
Acute leukemia:
Derived from blast-type cells
• Rapid advancement
• Often observed in children
Chronic leukemia:
Derived from later cell stages
• Slow advancement
• Often observed in elderly
Symptoms:
• Anemia / bleeding problems
• Fever / weight-loss
• Frequent infections
Treatment:
• Irradiation
• Chemotherapy
• Bone marrow transplant
Mononucleosis:
Excessive number of
agranulocytes
Epstein-Barr
virus
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D) Platelets (thrombocytes)
Blood Components:
Cardiovascular System – Blood
• Cytoplasmic fragments (anucleate)
• Function in blood clotting (contain clotting chemicals)
• ~ 150,000 – 400,000 / l
Hemocytoblast (stem cell)
Myeloid stem cell
Megakaryoblast Megakaryocyte Platelets
Hormone:
Thrombopoietin
Thrombopoiesis (platelet formation):
• Lifespan = ~ 10 days
(+)
Repeat mitosis;
no cytokinesis
Hemostasis (“stoppage of bleeding”):
Cardiovascular System – Blood
• Series of fast, localized reactions to halt blood loss
Phase 1:
Vascular spasm
Activated by:
1) Direct injury to smooth muscle
2) Chemical release (endothelial cells)
3) Nociceptors
Vasoconstriction of damaged vessel
(significantly reduces blood loss)
Phase 2:
Platelet plug formation
Temporarily seals vessel break
(positive feedback loop)
Intact endothelial cells release nitric oxide
and prostacyclin which prevent platelet
aggregation in undamaged tissue
Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figures17.13
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Hemostasis (“stoppage of bleeding”):
Cardiovascular System – Blood
Rupture of vessel
Platelet plug formation:
Collagen exposed
Platelets stick to collagen
von Willebrand factor:
Large plasma protein; links
platelets to collagen fibers Platelets swell and form
spiked processes
Platelets release contents
Adenosine
diphosphate (ADP)
Attracts more
platelets
(+)
Serotonin
Vascular spasms
Thromboxane
A2
Aspirin
Hemostasis (“stoppage of bleeding”):
Cardiovascular System – Blood
• Series of fast, localized reactions to halt blood loss
Phase 3:
Coagulation (blood clotting)
Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figures17.14
Blood converted from liquid to gel
(3 – 6 minutes)
• Requires clotting factors (procoagulants) Activation turns
clotting factors into
enzymes
Step 1:
Formation of prothrombin
activator
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Hemostasis (“stoppage of bleeding”):
Cardiovascular System – Blood
• Series of fast, localized reactions to halt blood loss
Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figures17.14
Activation turns
clotting factors into
enzymes
Step 1:
Formation of prothrombin
activator
(all factors found within blood) (requires factor outside blood)
Intrinsic pathway:
• triggered by negatively charged surfaces
(platelets / collagen / glass)
• Slow due to many intermediate steps
Extrinsic pathway:
• triggered by factor found in tissues under
the damaged endothelium (tissue factor)
• Rapid due to few intermediate steps Severe trauma:
15 seconds
Both pathways cascade to activation
of Factor X which combines with Platelet
Factor 3 (PF3), Ca++, and Factor V to form
Prothrombin Activator
Found on surface
of platelets
Hemostasis (“stoppage of bleeding”):
Cardiovascular System – Blood
• Series of fast, localized reactions to halt blood loss
Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figures17.14
Step 2:
Formation of thrombin
Step 3:
Formation of fibrin mesh
Factor XIII (fibrin stabilizing factor):
Cross-linking enzyme that binds fibrin
strands together
Anticoagulants:
Factors that inhibit clotting (e.g., heparin)
• Inactivated by antithrombin III
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Hemostasis (“stoppage of bleeding”):
Cardiovascular System – Blood
Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Table 17.3
= requires vitamin K
for synthesis
Hemostasis (“stoppage of bleeding”):
Cardiovascular System – Blood
• Series of fast, localized reactions to halt blood loss
Clot Retraction / Repair:
(30 – 60 minutes following damage)
• Platelets contain actin / myosin fibers;
contract in manner of muscle fibers
(draws ruptured edges of blood
vessel closer together)
Platelet-derived growth factor:
Released by platelets; stimulates smooth
muscle cells and fibroblasts to divide and
rebuild vessel wall
• Process of removing clot once healing
has occurred
Plasmin:
Fibrin-digesting enzyme (‘clot buster’)
Fibrinolysis:
Plasminogen Plasmin
(incorporated
into clot)
tissue plasminogen
activator (tPA)
(released by
endothelial cells)
(2 days following damage)
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Cardiovascular System – Blood
Thromboembolic Disorders
(undesirable clot formation)
Hemostasis (“stoppage of bleeding”):
Disorders of Hemostasis:
Thrombus:
A clot develops in an
unbroken blood vessel
Embolus:
A free-floating clot in
the bloodstream
(may lead to embolism)
Causes:
• Roughened endothelium (e.g., atherosclerosis)
• Slowly flowing blood (e.g., airlines - economy class)
Bleeding Disorders
(abnormal bleeding due to inability to clot)
Thrombocytopenia
• Deficiency in platelets
• Marrow destruction
Impaired Liver Function
• Vitamin K deficiency
• Cirrhosis / hepatitis
Petechiae
Hemophilia
• Missing clotting factor(s)
• Genetic (e.g., X-linked)
Hemophilia:
Hemophilia A
Factor VIII deficiency
77% of cases
Hemophilia B
Factor IX deficiency
Hemophilia C
Factor XI deficiency
(less severe)
Cardiovascular System – Blood
Symptoms:
• Prolonged bleeding
• Disabled / painful joints
Treatment:
• Plasma transfusions
• Injection of clotting factor(s)