Blood consists of ___

Plasma and formed elements

Plasma (46-63%) composition

- Plasma proteins (7%)

- Other solutes (1%)

- Water (92%)- transports organic and inorganic molecules, formed elements, and heat

Plasma proteins

- Albumin (60%)- osmotic pressure; transport lipids, hormones, and steroids

- Globulins (35%)- transport immunoglobulins (antibodies) and other globulins

- Fibrinogen (4%)- essential for clotting

- Regulatory proteins (<1%)- enzymes, proenzymes, hormones

Other solutes

Electrolytes, organic nutrients, organic wastes

Formed elements (37%-54%)

- Platelets and white blood cells (0.1%)

- Red blood cells (99.9%)

Platelets

Fragments of megakaryocytes critical for clotting

WBC- leukocytes- defense against infection

- Neutrophils (50-70%)

- Eosinophils (2-4%)

- Basophils (<1%)

- Lymphocytes (20-30%)

- Monocytes (3-8%)

Red blood cells

Erythrocytes deliver O2 and remove CO2

Components of plasma: water

- More than 90% of plasma by volume

- Helps blood function as temperature buffer (absorbs heat)

Components of plasma: plasma proteins

- Albumin: too large to leave the bloodstream; regulate osmolarity and function as carrier molecules

- Globulins: also function as carrier proteins

- Clotting factors: play an essential role in blood clotting

- Water soluble hormones

___ ___ include cells and their fragments

Formed elements

Buffy coat

- Leukocytes <0.01%

- Thrombocytes <0.01%

- Erythrocytes 99.9%

Erythrocyte ___ complements functions

Structure

Biconcave shape allows RBCs to —

Bend, fold and stack to prevent blockage in tiny blood vessels

Biconcavity also increases ___

Surface area for gas exchange

Anucleate

Non-mitotic, carry very little DNA, unable to synthesize proteins

Erythrocytes are prone to ___

Apoptosis

___ is the process of red blood cell formation

Erythropoiesis

Erythropoiesis

- Hematopoietic stem cell

- Myeloid stem cell

- Proerythroblast

- Basophilic erythroblast

- Polychromatic erythroblast

- Orthochromatic erythroblast -> nucleus ejection

- Reticulocyte

- Mature erythrocyte

Erythropoiesis is ___

Increasing hemoglobin, organelle degradation, decreasing size of nucleus

Regulation of erythropoiesis by ___

EPO

Hypoxia and testosterone both ___

Signal EPO release

EPO drives ___

Erythrocyte maturation

Blood doping

Artificially inducing polycythemia by taking testosterone, EPO or highly-packed RBC suspensions

Anemia

Blood disorders characterized by the body's failure to supply tissues with adequate O2

___ reversibly binds to blood gases within erythrocytes

Hemoglobin

Features of hemoglobin

- Globular, tetrameric protein formed from 2 alpha and 2 beta chains (adult) or 2 alpha and 2 gamma chains (fetus)

- Each contains a heme group that binds oxygen using iron

- Binding sites for O2 are cooperative

Oxyhemoglobin

Bound to O2

Deoxyhemoglobin

No O2 bound

Sickle cell anemia

- Most common heritable blood disorder

- Mutation causes mis-folded beta chain, polymerization of hemoglobin and change of the RBC's shape

- Sickled RBCs are prone to clogging and have decreased ability to unload O2

Sickle cell anemia: causes

- Single point mutation in beta globin gene

- Passed on as a survival advantage in regions with high rates of malaria

Iron from erythrocytes is ___ ___ in the body

Carefully recycles

Fate of heme

- Heme converted to biliverdin, then bilirubin

- Bilirubin transported through plasma to liver; incorporated into bile

- In intestine, bilirubin is converted to stercobilin and incorporated into feces

Fate of iron

Iron is bound to transferrin, then transported to bone marrow for erythropoiesis

General characteristics of leukocytes

- Nucleated, have membrane-bound organelles, do not contain hemoglobin

- Move through amoeboid motion

- Move in response to chemical signals (chemotaxis)

- Form transient bonds to blood vessels using adhesion receptors (margination)

- Can slip between endothelial cells (diapedesis)

Neutrophils (physical characteristics)

- Large and polymorphonuclear

- Light purple when stained and viewed under microscope

Neutrophils

- Efficient killers of bacteria

- Granules contain hydrolytic enzymes, defensins (antimicrobial peptides) and lysozyme (digests bacterial cell wall)

Eosinophils (physical characteristics)

- Large with bi-lobed nuclei; stain bright red with acidic dye eosin

- Secrete four distinct cationic proteins that exert a range of effects

Eosinophils

- Combat multicellular parasites (ex: flatworms)

- Also contribute to allergies/asthma

Basophils (physical characteristics)

- Have bi-lobed nuclei; stain dark blue with basic dyes

- Granules contain histamine, serotonin, heparin and prostaglandins

Basophils

- Play a supporting role at sites of infection

- Also contribute to allergies and anaphylaxis

Lymphocytes (physical characteristics)

- Smallest leukocyte; have single nucleus

- Stain dark blue and purple

Lymphocytes

- B-lymphocytes: responsible for producing antibodies

- T-lymphocytes: defend against abnormal, cancerous or virus-infected cells

Monocytes (physical characteristics)

- Largest leukocyte; have U-shaped nucleus and stain dark blue and purple

Monocytes

- Exit circulation and transform into macrophages, which engulf foreign invaders by phagocytosis

- Can be grouped into inflammatory macrophages or non-inflammatory macrophages

Mononucleosis (kissing disease)

Causes:

- Infection: most likely EBV

- Virus is transmitted through saliva, semen and blood

Symptoms:

- Flu-like symptoms

- Virus causes T cells to enlarge as they fight infected cells, resembling monocytes

Blood type

Determined by carbohydrate markers on plasma membrane of erythrocytes

Positive blood type

Presence of Rhesus factor

Negative blood type

Absence of Rhesus factor

AB+

Universal recipient

AB-

Can receive blood from:

O-, A-, B-, AB-

B+

Can receive blood from:

O-, O+, B-, B+

B-

Can receive blood from:

O-, B-

A+

Can receive blood from:

O-, O+, A-, A+

A-

Can receive blood from:

O-, A-

O+

Can receive blood from:

O-, O+

O-

Universal donor

Can receive blood from:

O-

Hemolytic disease of the newborn

Attack of fetal RBCs by maternal immune system leading to miscarriage

Causes of hemolytic disease of the newborn

- Fetus is Rh+ while mother is Rh-

- First pregnancy sensitizes mother, so anti-Rh antibodies are present for second pregnancy

- Anti-Rh antibodies are small enough to cross the placental barrier

Treatment for hemolytic disease of the newborn

Injection of anti-Rh antibodies into mother (destroy Rh+ cells before immune system can notice them)

___ is the process of stopping blood loss

Hemostasis

1. Vascular spasm phase

Vasoconstriction

- Immediately after a vessel is damaged, smooth muscle constricts to limit blood flow

- Initiated by endothelin, tissue factor and ADP

2. Platelet plug formation phase

- Platelets arrive at the site of damage and adhere to sticky endothelium

- Release chemical messengers thromboxane A2, ADP, Ca2+ ions and clotting factors

- Form platelet plug

- Promote wound healing

3. Coagulation (clotting) phase

Reinforcement of platelet plug by web-like protein mesh formed by fibrin

4. Clot retraction (stable clot)

Platelets contract to make the clot more compact and pull wound edges closer together

Human blood clotting

- Clotting factors activate prothrombin

- Prothrombin activates thrombin

-Thrombin activates fibrinogen (soluble), becomes insoluble

- Fibrin strands adhere to the plug to form an insoluble clot

Clotting factors are synthesized in the ___

Liver- vitamin K dependent process

Factors secreted as ___ to avoid inappropriate clotting

Zymogens

Activation of thrombin is important ___

- Drives the coagulation phase

- Multiple pathways to activation

- The intrinsic and extrinsic pathways converge at the common pathway

Common pathway

- Prothrombin activates thrombin, which activates fibrin, which creates a stable cot

- Thrombin creates a positive feedback loop with clotting factors 12 and 11

Anticoagulant pathway

- Prevent clotting

- Thrombin and thrombomodulin

- Protein C becomes activated by thrombin and thrombomodulin which inhibits clotting factor 12 which activates the anticoagulant

Fibrinolytic pathway

- Break down clots

- Plasminogen gets activated by tissue plasminogen activator, activates fibrin