Properties of BloodChapter 15

Large artery

Muscle

connective tissue

smaller artery

artery vs vein

arteriole

Capillaries

Blood can be divided into 2 componentsBlood can be divided into 2 components I. Plasma – fluid portion II. Formed elements – red and white blood cells and platelets (cell fragments)

Plasma – 55%Formed elements – 45% (mostly red blood cells)

I. Plasma 90% water 10% solutes proteins nutrients waste products gases electrolytes

Concentrations of small solutes are similar in plasma and interstitial fluid O2 and CO2 diffuse through membranes Water soluble materials diffuse through pores Concentrations of proteins are higher in plasma – capillaries are less permeable

* remember this?

Plasma Proteins – three main categories 1. albumins – generally used to transport materials like hormones most abundant of the plasma proteins synthesized by the liver 2. globulins – clotting proteins antibodies (gamma globulin) proteins that transport fat soluble hormones (steroid hormones) 3. fibrinogen – a filamentous protein from the liver, critical in clot formation

Other proteins in blood plasma include enzymes and hormones examples: angiotensinogen (liver), and renin (kidney)

Other solutes in blood plasma nutrients – absorbed from intestines sugars (glucose), amino acids, fatty acids, cholesterol, etc

waste products from cellular metabolism – urea, uric acid, etc

electrolytes – sodium, potassium, calcium, chloride, etc

gases – O2, CO2, N2

II. Formed elements in blood plasma red blood cells (erythrocytes Pronunciation: i-'rith-ro-sIts) white blood cells (leukocytes) platelets - pieces of bone marrow cells (megakaryocytes)

Blood cells produced in bone marrow children – marrow in all bones produces blood cells adults – only skull, chest, pelvis, long bones

Red blood cells 7 µm across 5,000,000 per cubic mm, Thus : 5,000,000,000 per cc (ml), 5,000,000,000,000 per liter, 25,000,000,000,000 per 5 liters lack a nucleus and mitochondria (what is their energy source?) have a large number of hemoglobin molecules (over 250,000,000 hemoglobin molecules per cell)

glycolysis

Hemoglobin Four subunits two α subunits, two β subunits Each subunit contains a heme group (the site where O2 binds to hemoglobin ) with one atom of iron one molecule of O2 binds to one iron atom CO2 binds to other sites on the hemoglobin molecule

ribbon model of hemoglobin

Production of red blood cells is regulated by erythropoietin hormone secreted by kidneys stimulates cell birth and maturation of erythrocyte precursor cells in bone marrow Breakdown of red blood cells happens in the liver and spleen breakdown products include bilirubin – gives yellow color to plasma and urine, and iron Lifetime is about 120 days (how many cells are born every day?)

~208,000,000,000 25 trillion cells / 120 days = 208 billion

Iron is supplied via dietary sources hemoglobin requires about 15mg of iron per 100ml blood (750mg / 5 liters) much of the iron is recycled from the liver

Iron-deficiency anemia When iron levels drop below what is required by hemoglobin, the blood’s capacity to carry O2 decreases

Pernicious anemia Low levels of vitamin B12vitamin B12 reduce levels of red blood cell birth B12 is essential for making DNA in dividing cells (and in maintaining myelin in nerve cells) remember that a huge number of red blood cells must be born every day B12 comes from meat, eggs, dairy products, or supplements

Blood loss is another cause of anemia

Symptoms: chronic fatigue, shortness of breath

Hematocrit (hct)

the percentage of blood volume that is red blood cells usually about 45%

determined by spinning the blood – the red blood cells are denser so they collect at the bottom

Scanning Electron Micrograph (SEM) of white blood cells attacking a cancer cell.

White blood cells

White blood cells Far fewer than red blood cells (1/1000 the number) Lifetime – a few days to a few weeks Found in blood and outside of blood • can squeeze through capillary pores • can move on their own 5 types of white blood cells Involved in immune response (more later)

5 types of white blood cells

Platelets pieces of bone marrow cells (megakaryocytes) critical role in blood clotting

• Around 100,000,000,000 platelets are produced each day• Lifespan: 7-10 days

Hemostasis: mechanisms that stop bleeding three steps 1) vascular spasm 2) platelet plug formation 3) blood clot formation

Vascular spasm • remember that injury triggers sympathetic inputs that trigger vasoconstriction? • there are also local chemicals that trigger vasoconstriction (vascular spasm) brief constriction of arterioles to reduce bleeding • antagonizes vasodilation from other local chemicals (inflamation)

(inappropriate vascular spasms are bad – reduced blood flow eg migraine)

Platelet plug formation platelet adhesion – platelets stick to tissues under the endothelial cells that line vessels von Willebrand factor is a plasma protein that binds platelets to the injured area von Willebrand factor is secreted by bone marrow cells, platelets, and endothelial cells 1) binds to collagen fibers (the basement membrane of the endothelial cells 2) then binds to platelets 3) triggers platelets to become sticky and to secrete other chemicals

von Willebrand factor triggers platelets to secrete chemicals • epinephrine and serotonin local vasoconstriction, temporarily opposes vasodilation • ADP causes platelet membranes to stick to each other initiates positive feedback: more platelets, more ADP, etc

ADP also triggers platelet membrane to release TXA2 (thromboxane A2)

TXA2 promotes • vasoconstriction • platelet stickiness • release of ADP (poss. feedback)

Platelets contain actin and myosin – sticking together triggers tightening

Platelet plug formation is actively inhibited by uninjured endothelial cells

Nitric oxide and prostacyclin inhibit plug formation • continuously released by endothelial cells (remember we said nitric oxide was continuously released ?)

Blood clot formation 1) involves a cascade of enzymatic events 2) results in formation of a sticky meshwork of fibrin proteins

Fibrin is the activated form of the plasma protein fibrinogen (which we mentioned earlier)

Fibrinogen is activated to fibrinby another protein, thrombin

Fibrin first forms a loose meshwork that is stabilized by factor XIIIa

End part of the coagulation cascade

Note that thrombin activates both fibrinogen and factor XIII (the “a” indicates activated form)

Thrombin is activated by yet another protein, factor Xa, and thrombinitself promotes activationof factor Xa (positive feedback)

There are two pathways to thrombin activation An intrinsic pathway (beginning in the vessel) An extrinsic pathway (beginning in nearby tissue)

Usually activated together since tissue damage outside of vessels usually occurs when vessels are damaged

Intrinsic pathwayIntrinsic pathway Begins when blood contacts collagen Activates factor XII XIIa Etc.

Note that Platelet Factor 3 (PF3) is necessary PF3 is secreted from activated platelets in the platelet plug (why important?)

PF3PF3

PF3PF3

• coagulation factors circulate in the plasma (most from liver)• numbers DO NOT correspond to their location in the sequence

Extrinsic pathwayExtrinsic pathway Begins when blood contacts factors from nearby damaged cells

from damaged tissue

in blood

Why use a cascade?Why use a cascade?Is there some advantage? Is there some advantage?

ping pong balls and mouse traps see youtube demo of chain reaction

http://www.stago.fr/Commun/img/NotreEnt/Thrombose_normal.mpg

Thrombus - A blood clot that forms in a vein and remains there. Embolus - A thrombus that travels from the vein where it formed to another location. Deep vein thrombosis - A blood clot occurring in a leg or pelvic vein. Pulmonary embolism - a blood clot that has traveled to the lungs.

blood-filled infarcted (dead) lung tissue

late stem cell stem cell in bone marrow

proerthroblast (fate determined)

basophilic erythroblast(size decreases)

Erythropoiesis

polychromatophilic erythroblastnow producing hemoglobin

ready to extrude its nucleus

mature erythrocyte

mature erythrocyte

extruding its nucleus mature erythrocytesready to enter the blood

cell nucleus