ANP 1115 - Blood (Pt. 1) Flashcards
What is the ONLY Fluid Tissue in the Body?
Blood is the only FLUID tissue in the body
Where are Formed Elements suspended in?
Suspended in Plasma
What are the Cellular Components of Blood?
- Fluid Matrix —> Located between cells
- Fibrin Threads —> Formed during blood clotting (for more fluid)
What are the Formed Elements of Blood (and their functions)?
- Erythrocytes (RBCs) —> Transport oxygen
- Leucocytes (WBCs) —> Protection against invading microorganisms; clears cellular debris
- Platelets —> Formation of blood clots
What are the Physical Characteristics of Blood?
- Colour is scarlet (O2 rich) to dark red (O2 poor)
- More dense (millions cells / um blood), viscous than H2O
- pH - 7.35-7.45 (mechanisms for homeostasis)
- ~8% body weight (5-6 L male; 4-5L female)
What are the Three Functions of Blood?
- Distribution
- Regulation
- Protection
What is Distribution of Blood?
a) oxygen & nutrients (to tissue; from digestive tract to liver)
b) metabolic wastes (kidney to lungs for CO2)
c) hormones)
What is Regulation of Blood?
a) body temperature: distribution, conservation , dissipation (circulatory system; blood carries heat)
b) pH in body tissues (plasma proteins, bicarbonate reserve)
c) adequate fluid volume
What are the Protections for Blood?
a) Platelets, plasma proteins (protection against blood loss)
b) Antibodies, complement, WBCs (protection against infection; immune system)
What is Blood Plasma?
- Straw coloured
- 90% water + many solutes (ions, plasma proteins)
What are Plasma Proteins?
Functional proteins which remain in blood
- Produced in the liver (except gamma globulins which are antibodies - instead is produced by immune system)
What is Albumin?
- 60% of all plasma proteins
- carrier of various molecules
- important blood buffer (can take in additional H+)
- major osmotic protein
What is the Major Osmotic ion?
Sodium ion:
- Most prevalent ion in the blood stream
- Ensures enough fluid in blood
Why is Blood constantly adjusted?
Blood is constantly adjusted to keep its composition, pH within normal range
What percentage of Blood is composed of Plasma?
55% (least dense component)
What does the Buffy Coat consist of?
Leukocytes and platelets
- <1% of whole blood
What percentage of Blood is composed of Erythrocytes?
45% (most dense component)
Why do we say that Leukocytes only are complete cells?
Leukocytes contain nuclei
- Nuclei removed for other blood components when leaving blood stream
What are Formed Elements replaced by?
Most formed elements are short-lived / disposable
- constantly replaced by bone marrow
What are the characteristics of an Erythrocyte?
- ~7.5 um diameter
- biconcave discs (no nucleus) = “bags of hemoglobin”
- other proteins maintain PM, regulate cell shape
What is the function of Spectrin
revisit
What do RBCs transport?
RBSc transport O2 from lungs to tissues
- transport 20% of CO2 back to lungs (rest is transported directly in plasma)
What are the Specialized Characteristics that Optimize function?
- small size & biconcave shape gives large SA to V ratio
- > 97% non-water composition is hemoglobin
- no mitochondria; generate ATP anaerobically
What is the Major factor that contributes to Blood Viscosity?
RBCs are the major factor contributing to blood viscosity
What is the relation of RBC count between men and women?
Women have lower RBC count than men
What is the relation between rate of Blood Flow to RBC count?
Rate of blood flow is inversely affected by RBC count
What is Hemoglobin (Hb)?
A protein globin bound to red heme pigment
What is a Globin?
4 polypeptide chains (2 alpha, 2 beta)
- 4 Fe containing central heme groups
What can each Iron group do wrt oxygen?
Each Fe can reversible bind one molecule of oxygen
- 4 per Hb molecule
How many Hb molecules do each RBC contain?
Each RBC contains 250 million Hb molecules
Where is Hb contained in and why?
Hb is contained in erythrocytes rather than being a plasma protein:
- keeps it from fragmenting and being lost
- keeps it from contributing directly to osmotic pressure & blood viscosity
What is the difference between oxyHb and deoxyHb?
oxyHb is a different shape and colour than deoxyHb
How do O2 and CO2 interact with Hemoglobin?
- O2 combines with heme group
- CO2 combines with globin to form carbaminohemoglobin
*CO2 does not compete with O2
What is Hematopoiesis?
The production of formed elements in red bone marrow
- RBCs are immature
What happens to RBCs when they become mature?
Migration through capillary walls to the blood
What are Hematopoietic Stem Cells?
Hemocytoblast: Stem cell for all formed elements; immature cells become committed to a particular pathway
What is Erythropoiesis?
Production of RBCs (erythrocytes) in red bone marrow
- process takes roughly 15 days and is composed of 3 steps or phases
What are Proerythroblasts?
Committed cells that fill up with hemoglobin and discards nucleus
How do Proerythrocytes undergo protein synthesis?
Use of ribosomes for protein synthesis
- beta subunits
- alpha subunits
What are Reticulocytes?
New RBCs that move out to circulation
What happens to the Protein Synthetic Machinery in Reticulocytes?
Protein synthetic machinery broken down + digested in 24 - 48 hours
How long do RBC last?
100 - 120 days
What is the difference between a reticulocytes and an erythrocyte?
reticulocyte contains residual synthetic machinery
- called erythrocyte when synthetic machinery is gone
What does a Low Reticulocyte count tell you?
Could be anemic
What does a High Reticulocyte count mean?
Production of new RBC is stimulated
What would a Reticulocyte Count tell you?
- Provides information on the bone marrow’s ability to produce new RBCs
- Helps distinguish between various causes of anemia
- Helps monitor bone marrow response and the return of normal marrow function following treatment
What is the mechanism for Regulation of Erythropoiesis?
- Balance between RBC production & destruction
- Too few: anemia; too many: polycythemia
- production rate: >2 million / sec if healthy (sufficient iron & B vitamins)
What is Erythropoietin?
EPO, glycoprotein hormone produced primarily by the kidney
- always some EPO in blood
- stimulates RBC production in bone marrow
What are the effects of Hypoxia on EPO?
Additional release if hypoxia due to:
1. hemorrhage / excess RBC destruction
2. high altitude or pneumonia
3. Increased demand
What is monitored and acts as a signal for EPO?
the level of oxygen transport
What are the effects of Erythropoietin?
Enhances maturation rate of RBC precursors
- (1-2 days to see increased release of reticulocytes and their maturation to RBCs)
What are the additional problems of Renal Failure Patients?
additional problem is a lack of EPO
- RBC counts can be 50% of normal
- helped by recombinant EPO
What are the effects of EPO abuse?
Can increases hematocrit from 45% to 65%
- increased viscosity plus dehydration during a race can cause clotting, stroke, heart failure
What is the Effect of Testosterone on renal EPO production?
Stimulatory: EPO stimulated for production of RBCs
What is the second reason why women have a lower hematocrit than men?
Loss of blood due to menstruation
What are the Dietary Requirement for erythropoiesis?
- Iron
- B-Vitamins
What is the Absorption of Dietary Iron controlled by?
Controlled by the body’s storage levels
Where is Dietary Iron stored?
- 65% already in molecules of Hb
- rest is stored in liver, spleen, bone marrow (ferritin, hemosiderin)
What is Iron transported in blood bounded to?
Iron transported in blood loosely bound to transferrin
What is Loss of Iron caused by?
Loss of iron: via feces, urine, sweat, menstrual fluid in females aged 12-52
average daily loss: 1.7 mg (female), 0.9 mg (male)
What is essential for DNA synthesis?
vitamin B12 & Folic acid are essential for DNA synthesis
Why do Mature Erythrocytes become rigid, fragile with time?
Hemoglobin begins to degenerate
What is the Useful Life Span of Erythrocytes?
100 - 120 days
What is the Spleen often referred to as?
RBC graveyard
What is the Result of the Destruction of Erythrocytes?
- Iron stored & reused
- rest of heme degraded to bilirubin
- Amino acids of globin part recycled (reused)
What happens to Bilirubin?
Eventually becomes stercobilin or unobilinogen
What is Anemia?
reduced oxygen carrying capacity of blood
What are the Three causes to Anemia?
- Not enough normal RBCs produced
- Episode of significant blood loss
- RBCs are being too quickly destroyed (sickle cell anemia)
What is Polycythemia?
Elevated number of RBCs
What is Polycythemia Vera?
“True polycythemia” due to a cancerous condition in bone marrow
What is Secondary Polycythemia caused by?
Due to high altitude
- Kidney senses reduced oxygen delivery (e.g., atmospheric air)
- increase release of EPO
What is Artificial Polycythemia?
Blood doping
- Taking additional EPO when not needed
- Boosting level of RBCs artificially in circulatory system
What are Platelets?
Cytoplasmic fragments of megakaryocytes
- anucleate
What do Platelets contain?
contain purple-staining granules that contain clotting factors & enzymes
What is the Lifespan of Platelets?
~10 days
What is Platelet Formation regulated by?
Regulated by the hormone Thrombopoietin
Where is Thrombopoietin produced?
- Liver is the primary source
- Kidney’s (mainly the primary source of erythropoietin)
How many Platelets per microlitre of blood?
150 000 - 400 000
What is HEMOstasis?
Process of making a blood clot
What are the Three Phases of Hemostasis?
a) vascular spasms
b) formation of platelet plug
c) coagulation
What are Vascular Spasms?
Brief vasoconstriction of vessel in response to damage
- slow down blood flow
- Allows platelets to easily interact, activate, and release clotting factors in vesicles (vessels?) for blood clots
What are the Triggers to Vascular Spasms?
- Damage to the wall of the vessel
- chemicals from damaged endothelial cells & activated platelets
- reflexes activated by local pain receptors
Why do Platelets have difficulty grouping together or sticking to Endothelial Linings?
platelets do not stick to each other or to endothelial linings due to production of NO and PGI2 (prostacyclin) by endothelial cells
*NO and PGI2 prevents blood clot when there is no damage
What does the Exposure to Collagen stimulate in Hemostasis?
exposure to collagen (in basement membrane of endothelial cells) stimulates platelets to swell
- become spiky & sticky
How do Platelets adhere to exposed Collagen and what does it lead to?
adhere to exposed collagen via von Willebrand factor
(a plasma protein; helps platelets adhere to collagen)
Leads to: degranulation and a lot of positive feedback
What is Degranulation?
Release of clotting factors from platelet granules
What are the Platelet Products that promote clumping?
ADP: enhances aggregation and degranulation
Serotonin: a neurotransmitter but also a platelet product
Thromboxane A2 (a prostaglandin): enhance vascular spasm
& aggregation
What happens during Coagulation?
platelet plug converted to a much sturdier structure
What are the Three phases of Coagulation?
- prothrombin activator formed
- prothrombin converted to thrombin
- fibrinogen molecules → fibrin mesh
What are the Two Pathways to Prothrombin Activator & Coagulation?
- Intrinsic pathway
- Extrinsic pathway
What is the Intrinsic Pathway?
Clotting of blood OUTSIDE the body (in a tube) or in a slightly damaged vessel
- slower pathway to factor X and PA
- Exposure to collagen is key
What is the Extrinsic Pathway?
Clotting of blood in response to damage
- release of tissue factor
- bypass many steps of intrinsic pathway
- faster pathway to factor X and PA
What does Prothrombin Activator consist of?
Consists of factors Xa, Va, Ca, phospholipid surface
What is the Rate Limiting Step of Clot formation?
Prothrombin Activator (PA) is the rate-limiting
step
- once achieved, clot formation in 10-15 sec via Phase 2 & 3 common pathways
When do Clot Retraction and Repair occur and how?
Occurs within 30-60 mins
- Platelets contract (contain actin & myosin)
- exerts pulling force on surrounding fibrin strands
What is Serum and where does it come from?
Fluid that is plasma minus the clotting factors
- Squeezed from clot & ruptured edges of blood vessels pulled closer
When is PDGF released?
Platelet-derived Growth Factor
- released during degranulation
What does PDGF stimulate?
Stimulates smooth muscle cells & fibroblasts to divide & rebuild wall
- endothelial cells multiply to fill gap in lining (VEGF)
- the clot covers the area of damage while healing begins
What is VEGF?
Vascular Endothelial Growth Factor
- Production of new endothelial cells to line blood vessel
