Blood Flashcards
List the functions of blood
- Transport respiratory gases (O2 &CO2)
- Transports nutrients, electrolytes, vitamins, hormones, lipids, wastes
- Regulation (Homeostasis) of body temperature, pH, ion concentration, osmolality, hormones
- Hemostasis to prevent blood loss
- Immunity (leukocytes)
How does blood regulate body temperature?
Through the re-distribution of heat
Carries heat away from where it is being produced (e.g. during exercise)
What is hemostasis?
Complex and efficient pathways to prevent blood loss from a damaged blood vessel and tissue repair
Platelets + Coagulation
How much blood does an average adult have?
Average: 5L
Men: 5-6L
Women: 4.5-5.5L
Why is blood 5x more viscous than water?
Blood consists of water, dissolved proteins & formed elements
What are the components of blood?
RBC
WBC
Platelets
Plasma
What constitutes of formed elements?
Cellular components:
RBC, WBC, Platelets
Plasma composition in %
Plasma proteins 7%
Other solutes 1%
Water 92%
List the composition of plasma proteins (in order of their abundance, from mosts to least)
- Albumin (60%)
- Globulins (35%)
- Fibrinogen (4%)
- Regulatory proteins (<1%)
% don’t need to know
Purpose of albumins
(plasma protein)
- major contributors to osmotic pressure of plasma (maintain)
- tpt lipids & steroid hormones
Purpose of globulins
(plasma protein)
- tpt ions, hormones, lipids
- immune function (immunoglobulin)
Purpose of fibrinogen
(plasma protein)
- Essential component of clotting system; can be converted to insoluble fibrin
What are regulatory proteins?
Enzymes, proenzymes, hormones
What are the other solutes in plasma?
- Electrolytes
- Organic nutrients
- Organic wastes
What are the major plasma electrolytes?
- NA+ (sodium)
- K+ (potassium)
- CA2+ (calcium)
- Mg2+ (Magnesium)
- Cl- (Chloride)
- HCO3- (bicarbonate)
- HPO4- (hydrogen phosphate)
- SO42- (sulfate ion)
What do electrolytes in the plasma do?
Ions contribute to osmotic pressure of body fluids
What are the organic nutrients in the plasma used for? What do they include?
Used for ATP production, growth, maintenance of cells
Includes:
1. Lipids (fatty acids, cholesterol, glycerides)
2. Carbs (primarily glucose)
3. Amino acids
What happens to the organic wastes in plasma? What do they include?
Carried to sites of breakdown/excretion
Includes:
1. urea
2. uric acid
3. creatinine
4. bilirubin
5. ammonium ions
Normal hematocrit levels for males & females
Males: 40-54%
Females: 37-47%
Normaal hemoglobin levels for males & females
Males: 14-17 g Hb/dL
Females: 12-16 g Hb/dL
What does hemoglobin value reflect?
The oxygen-carrying capacity of RBCs
What is hematocrit?
% of total blood volume that is occupied by packed (centrifuged) RBCs
Breakdown the % of a complete blood count (Plasma, WBC, RBC)
Plasma: ~58%
WBC: <1%
RBC: 42%
Name the differential WBCs
- Neutrophils
- Eosinophils
- Basophihls
- Lymphocytes
- Monocytes
List the differential WBCs according to abundance, starting with the most abundant.
- Neutrophils (50-70%)
- Lymphocytes (20-40%)
- Monocytes (2-8%)
- Eosinophils (1-4%)
- Basophils (<1%)
Don’t need to know %
List the function of RBCs
- Respiratory gas transport
contains Hb to tpt O2
contains carbonic anhydrase to tpt CO2 - buffer pH in blood
Shape of RBCs
Biconcave discs
Size of RBCs
Diameter: 7.5µm
Thickness: 2.5-0.5µm
Adaptation of RBC
- Large surface to volume ratio which optimises gas exchange and allows easy diffusion of O2
- Flexibility -> allows RBCs to move smoothly through capillaries (small: 3-4µm diameter) through stack formation
Composition of RBCs
Mainly Hb
No nucleus
No organelles
How many % of the formed elements in blood are RBCs?
> 99%
Remaining ~1% are WBC & platelets
RBC lifespan
100-120 days
How much % of RBC content is Hb?
> 97%
How does more Hb in blood help?
More Hb = inc O2 tpt capacity = less work for the heart as a pump
How does RBCs get energy?
Glycolysis (anaerobic) for ATP -> fuel active tpt mechanisms to maintain ionic conc. within cell
Lack mitochondria (bc produicing ATP requires O2 -> not efficient bc consumption of tpted O2)
What does carbonic anhydrase do?
Converts CO2 into bicarbonate (HCO3) -> primary form of CO2 in blood
Chemical eqn of conversion of CO2 in the presence of carbonic anhydrase
CO2 + H2O <-> H2CO3 <-> H+ + HCO3-
H2CO3 is carbonic acid -> not stable so degenerates
What does it mean for the cell that it has no nucleus?
No nucleus mean s no ribosomes
No repairs or division/synthesis of cellular proteins/enzymes
E.g. damage/wear & tear from squeezing through capillaries
What are the two portions of Hemoglobin?
Globin portion
Heme molecule
What is the globin portion of hemoglobin?
4 folded polypeptide chains (2 alpha + 2 beta chains) -> each chain contains a single heme molecule
What is the heme molecule?
Pigment complex
1 iron -> 1 O2 molecule can bind
Binding is weak & reversible
How many molecules of oxygen can one Hb molecule transport?
4
Sites of Erythropoiesis
Fetus: yolk sac, developing liver & spleen
Children: bone marrow in many different bones
Adults: bone marrow in ribs, sternum, vertebrae, pelvis & upper end of long bones
Steps of Erythropoiesis
- Hematopoietic stem cells in bone marrow give rise to proerythroblasts
- Proerythroblast develop into erythroblasts
- Ribosome synthesis occurs in early erythroblasts to make Hb
- Hb accumulates in late erythroblasts & normoblasts
- Ejection of nucleus from normoblasts and formation of reticulocytes
- Reticulocytes continue Hb synthesis, leave bone marrow & complete differentiation to mature RBC in blood
What is reticulocyte count indicative of?
Indicative of erythropoiesis
Reticulocyte count normal range
0.8-1.5%
What does erythropoiesis require?
- Iron
- Vitamin B12
- Folic acid/folate
- Proteins
- Lipids
- Carbs
How much iron does a normal diet provide and how much is absorbed?
Provides 10-15 mg/day
10% absorbed
How much iron is lost per day?
0.5-1.0mg in males
greater in females
How to treat anemia?
Iron supplement, folic acid, Vitamin B12
Recco intake of Vitamin B12
2 microgram/day
Where is Vitamin B12 stored in body?
mainly in the liver
0.8-11mg
Dietary sources of Vitamin B12
Animal origins, esp liver, kidney
Minimum daily requirement of folate
50 microgram
How much of folate does the body store?
total body stores about 5-10 mg
Dietary sources of folate
green leafy veg, fruits, yeast, liver, kidney, dairy products
What are vitamin B12 and folate necessary for?
Synthesis of thymidylate (nucleotide of thymine in DNA)
What does deficiency of vitamin B12 and folate lead to?
Maturation failure of healthy RBCs (aka macrocytic anemia)
Steps in the homeostasis of blood oxygen levels (regulation of erythropoiesis)
- Stimulus: Hypoxia (inadequate O2 delivery)
due to:
- ↓ RBC count (hemorrhage/excessive RBC destruction)
- ↓ amt of hemoglobin (insufficient hemoglobin per RBC -> iron deficiency)
- ↓ availability of O2 (high altitude/hypoxia)
(increased tissue dd for o2) - Kidney (& liver to a small extent) releases erythropoietin
- Erythropoietin stimulates red bone marrow
- Enhanced erythropoiesis = ↑ RBC count
- O2-carrying ability of blood ↑
What is erythropoietin?
- Peptide hormone
- Messenger that travels from kidney to bone marrow
- About 90% secreted from kidney, 10% from liver
What does erythropoietin do?
- Stimulates hematopoietic stem cells to form proerythroblasts
- Enhances proliferation rate of proerythroblasts and erythroblasts
- Enhances Hb synthesis
- ↑ RBC production approx 10x
Why do men have higher RBC conc. than women?
Androgen contributes to erythropoiesis but not estrogen
What happens to the aged and damaged RBC?
Engulfed by macrophages of liver, spleen & bone marrow
Hemoglobin is broken down into heme and globin
- Heme is broken down to bilirubin -> excreted
- The iron in heme is also stored as ferritin -> recycled
- Globin broken down into a.a.
What is anemia?
Below normal O2-carrying capacity of blood (200ml O2/L)
- ↓ rate of erythropoiesis, excessive loss of RBC
- ↓ Hb in RBCs
What is microcytic anemia and cause?
RBCs are smaller than normal
Lack of iron -> required for erythropoiesis
What is macrocytic anemia and cause?
RBCs are bigger than normal, but lacking Hb
Lack of vitamin B12/folate
Veganism
What is aplastic anemia and cause?
Failure of bone marrow to make adequate numbers of RBCs even though all ingredients are available
E.g. Radiation damage/chemotherapy
What is polycythemia?
Excess in circulating RBCs
- Elevated hematocrit (normal HCT: 37-54%)
List the types of polycythemia
- Primary polycythemia
- Secondary polycythemia
- Relative polycythemia
List the types of anemia
- Macrocytic anemia
- Microcytic anemia
- Aplastic anemia
What is the cause of primary polycythemia and what are the Hct levels like?
Caused by a tumour or tumour-like condition of the bone marrow
Hct 70-80%
↑ RBCs/ml
What is secondary polycythemia and an example of a cause?
Erythropoietin-induced, adaptive mechanism to improve o2-carrying capacity of blood
↑ RBCs/ml
E.g. People living in high altitudes
What causes relative polycythemia?
Dehydration -> elevate hematocrit
RBC amount not changed but due to drop in plasma volume
What is the erythrocyte sedimentation rate (ESR)?
The time taken for erythrocytes to sediment
Erythrocytes sediment faster with ↑ed plasma protein conc.
What can ESR monitor?
Infection
Autoimmune diseases
inflammatory diseases
inexpensive way to monitor
ESR will ↑ (take longer to settle)
State the surface antigen for each blood type.
Blood type A: Surface antigen A
Blood type B: Surface antigen B
Blood type AB: Surface antigen A and B
Blood type O: None
State the antibodies present for each blood type.
Blood type A: Anti-B antibodies
Blood type B: Anti-A antibodies
Blood type AB: None
Blood type O: Anti-A and anti-B antibodies
What happens when there is a cross-reaction (e.g. donor has blood type A but recipient has blood type B)?
- Opposing antibodies will attack the surface antigens
- Agglutination on RBC surfaces occur
- Hemolysis occurs
What are some blood transfusion reactions?
Allergic
- Facial flushing
- Hives/rash
Febrile
- Headache
- Fever
- Chills
- Anxiety
- Tachycardia
- Tachypnea
Hemolytic (kidney damage)
- Headache
- Chest pain
- Apprehension
- Low back pain
- Chills
- Fever
- ↑ Resp rate
- ↓ bp
What are the Rh factors?
C (c), D (d), E (e)
What are the main steps when there is injury/damaged vessel?
- Vasoconstriction
- Formation of temporary platelet plug
- Blood coagulation
- Clot retraction & fibrinolysis
What is the Rh factor?
- 2nd most significant blood group
- Rh-D most likely to cause immune response during blood transfusion
- if you have + after your blood type (e.g. B+), you are Rh-D
What happens in the vasoconstriction phase?
When the blood vessel is damaged = exposes endothelial cells
1. Endothelial cells contract = expose the Basal Lamina to blood stream
- Endothelial cells begin releasing chemical factors & local hormones (tissue factor, ADP, thromboxane A2)
- stimulates smooth muscle contraction & vasoconstriction (↓ bld flow = allow platelets to slow down & bind to damaged areas)
- stimulates division of smooth muscle cells, endothelial cells & fibroblasts = tissue repair - Endothelial cell mbns become sticky = partial seal
What are platelets?
Fragments of megakaryocytes
Lifespan of abt 10 days = removed by phagocytes in spleen
Characteristics of platelets
- lack nuclei
- contain contractile proteins (actin & myosin)
- contain granules (ADP, Ca2+, growth factors - PDGF, VEGF = hormones that stimulate endothelial cells to grow/repair)
PDGF: platelet derived growth factor
VEGF: vascular endothelial growth factor
What happens during the platelet phase?
- Actin and myosin contract = forcing out the contents of platelet granules (becomes degranulated platelets)
- Circulating platelets adhere & are activated by exposed collagen at site of injury (von Willebrand factor)
- Activated platelets release ADP & Thromboxane A2
- These chemical messengers work together to activate other platelets passing by
- Newly activated platelets aggregate onto the growing platelet plug = release more platelet-attracting chemicals
- Normal (uninjured) endothelium releases prostacyclin & nitric oxide = inhibit platelet aggregation = platelet plug confined to site of injury
What happens in the coagulation phase?
- Fibrin forms a mesh that traps RBCs and platelets, forming the clot
What do degranulated platelets secrete?
- Thromboxane A2 (enhance vascular spasms)
- ADP (enhances platelet aggregation & secretion)
- Calcium (essential for blood clotting)
- PDGF (fibroblasts)
- VEGF (vascular endothelial cells)
- Factor XIII (FSF) (convert fibrin polymer to stable fibrin)
Where are all factors of the intrinsic, extrinsic and common pathway found?
plasma
Explain the steps of the intrinsic pathway
- Vessel endothelium rupture = expose underlying tissues (collagen) = platelets cling & their surfaces provide sites for mobilization of factors
- Factor XII (12) activated to XIIa (activated by collagen & substances released by platelets)
- Factor XI (11) activated to XIa (by Factor XIIa)
- IX (9) activated to IXa (by XIa and Ca2+)
- IXa + VIIIa = IXa/VIIIa complex
Common pathway
Explain the steps of the extrinsic pathway
- Tissue cell trauma causes release of Tissue factor (TF)
- TF activates VII to VIIa
- TF with VIIa and Ca2+ forms a TF/VIIa complex
Common pathway
Explain the steps in the common pathway
- IXa/VIIIa complex (intrinsic) or TF/VIIa complex (extrinsic) activates factor X to Xa
- Xa together with Ca2+ & PF3 & Va = prothrombin activator
- Prothrombin activator activates Prothrombin (factor II) to Thrombin (IIa)
- Thrombin (IIa) activates Fibrinogen (factor I) to Fibrin
- Thrombin (IIa) + Ca2+ activates factor XIII to XIIIa
- XIIIa activates fibrin to become a cross-linked fibrin polymer
What is Tissue Factor (TF)?
- transmembrane receptor for VII/VIIa
- Endothelium physically separates TF from circulating VIIa
- TF and VIIa initiates blood coagulation
Which clotting factors require vitamin K?
- Factor II
- Factor VII
- Factor IX
- Factor X
Where is the source of clotting factor III?
Damaged tissue
Activated platelets
Where is the source of clotting factor VIII?
Liver
Lung endothelial cells
Where is the source of clotting factor IV?
Bone
Diet
Platelets
Where is the source of clotting factor XIII?
Liver
Platelets
Which clotting factors are NOT from the liver?
- Factor III
- Factor IV
What is the role of thrombin in hemostasis?
- Converts fibrinogen to fibrin
- Activates Factor XIII = stabilises firbin mesh
- Enhances platelet aggregation (= secretes PF3 = releases tissue factor)
- Enhances activation of thrombin from prothrombin (positive feedback loop - self amplification)
Describe the process of clot dissolution (fibrinolysis)
- Plasminogen trapped inside clot during clot formation
- Plasminogen can be cleaved to plasmin by proteases (tPA, thrombin, Factor XII)
- Surrounding tissue & vascular endothelial cells release tissue plasminogen activator (tPA)
- tPA cleaves inactive plasminogen to plasmin
- Plasmin (is a protease) digests fibrin = dissolves clot
- Phagocytic WBCs remove remains of the clot (macrophages & neutrophils)
What is thromboembolism?
Inappropriate (abnormal) clotting
- e.g. roughened surface of a vessel, endothelial cell damage (post op)
Thrombi
Embolus
What is Thrombi?
- Solid masses/plugs form in the circulation (blood constituents, platelets & fibrin)
- Can block circulation = tissue death (e.g. deep vein thrombosis - DVT)
E.g. Coronary thrombosis: thrombus in blood vessel of heart -> blocks -> heart attack
What is an embolus?
- A thrombus freely floating in the blood stream
- E.g. pulmonary emboli (clot flows to lungs) = impair ability to obtain O2
- E.g. cerebral emboli (clot flows to brain) = strokes
State two blood clotting disorders
- Thrombocytopenia
- Hemophilia
What is thrombocytopenia?
- Circulating platelets is too low (<50 million/ml; normal is 150-350 million/ml)
- Causes spontaneous & widespread hemorrhage = visible as small purple spots on skin
- Cause: Suppression/destruction of bone marrow (e.g. cancer - malignancy, radiation)
What is hemophilia?
- A condition of excessive bleeding
- Cause: vitamin K deficiency
- Hereditary hemophilias cause: lack of clotting factors
Hemophilia A
Hemophilia B
Hemophilia C
What is prothrombin time?
Time for plasma sample to clot after adding Factor III (TF) and Factor IV (calcium)
What is the normal prothrombin time (PT)?
11-13 seconds
What is INR?
International Normalized Ratio
INR = (PT test / PT normal)^ISI
E.g. 45/12 = 3-4
What can prothrombin time assess?
How healthy the extrinsic & common pathway is
What is activated partial thromboplastin time (aPTT) ?
- Estimation of the intrinsic pathway
- Measures clotting time of plasma, by adding factor XII activators
What is the reference range of aPTT?
25-40 seconds
What are some anticoagulants?
- Heparin
- Anti-thrombin III
- Warfarin drugs
- Removal of calcium ions
How does heparin function?
co-factor to anti-thrombin III
How does anti-thrombin III function?
- plasma protein that binds to & inactivates thrombin (2a), IXa, Xa
How does warfarin drugs work?
- Vitamin K antagonists
- Reduce biological activity of vitamin K dependant coagulation factors
Vitamin K required for conversion of precursor forms of factors X, IX, VII, II (1972 = 10, 9, 7, 2)
List the leukocytes.
- Macrophage
- Dendritic cell
- Neutrophil
- Eosinophil
- Basophil
- Mast cell
What could a decrease in WBC indicate?
- some medication
- autoimmune disease
- bone marrow diseases
- severe infectionsW
What could an increase in WBC indicate?
- Infection (e.g. abscess, meningitis, pneumonia, appendicitis, tonsilitis)
- Inflammation
- Leukemia
- Stress
- Dead tissue (burns, heart attack, gangrene)
What does a decrease in platelet count?
- Not enough made
- Bleeding
- Systemic lupus erythematosus
- Pernicious anemia
- Hypersplenism
- Leukemia
- chemotherapy
What does an increase in platelet count mean?
- too many made
- young cells
Draw the intrinsic and common pathways for coagulation.
Refer to slide 38 of blood lecture
Draw the extrinsic and common pathways of coagulation.
Refer to slide 38 of blood lecture
What % of the body weight is blood?
8%
