1)Blood

• transports nutrients and wastes
• composed of plasma and variety of cells

2)Interstitial fluid

• bathes cells of the body

Nutrients and oxygen diffuse from

blood→ interstitial fluid→ cells

(waste opposite direction)

hematology- study of blood and blood disorders

• more viscous than water, flows more slowly
• 100.4°F- core body temperature
• pH 7.4
• 8% total body weight
• blood volume ≈ 5 liters
• maintained by hormones

transportation

• O₂, CO₂, metabolic wastes, nutrients, heat and hormones

regulation

• helps regulate 
• pH through buffers
• body temperature
• coolant properties of water
• vasodilation of surface vessels dump heat

protection from disease and loss of blood 

[image]components of blood[image]

hematocrit

• 55% plasma
• 45% cells
• 99% RBCs
• <1% WBCs and platelets

1. plasma
2. RBCs
3. buffy coat- WBCs and platelets

• over 90% water
• 7% plasma proteins
• created in liver
• confined to bloodstream
• albumin
• carrier protein
• important buffer
• maintain blood osmotic pressure
• globulins (immunoglobulins)
• antibodies bind to antigens (foreign substances)
• form antigen-antibody complexes
• fibrinogen
• for clotting
• 2% other substances
• electrolytes, nutrients, hormones, gases, waste products

• red blood cells (erythrocytes) 
• white blood cells (leukocytes)
• granular (contain packets that contain defensive chemicals)
• neutrophils 
• eosinophils
• basophils
• agranular (can have defensive chemicals just not contained in packets)
• lymphocytes
• T cells
• B cells 
• natural killer cells
• monocytes
• platelets
• special cell fragments formed from huge cell as it squeezes out of the red bone marrow after being produced
• important in clotting cascade- act like sand bags in a leak

• percentage of blood occupied by red blood cells (percent RBCs in blood by volume compared to otehr components)
• females have lower percentage than men because of lower testosterone levels and higher adipose levels
• anemia- not enough RBCs or not enough hemoglobin
• polycythemia- too many RBCs (over 65%)
• makes blood too viscous
• can be caused by dehydration, tissue hypoxia, blood doping 

• injecting previously stored RBCs before an athletic event
• more cells available to deliver oxygen to tissues
• dangerous
• increases blood viscoscity
• forces heart to work harder

• most blood cell types need to be continually replaced
• die within hours, days or weeks
• process of blood cell formation = hematopoiesis or hemopoiesis
• in embryo 
• occurs in yolk sac, liver, spleen, thymus, lymph nodes and red bone marrow (when bones finally develop)
• in adult
• occurs only in red marrow of flat bones like sternum, ribs, skull, pelvis and ends of long bones.

• pluripotent stem cell from red bone marrow can become any of the cellular elements
• lymphoid stem cells only give rise to the two different lymphocytes (T cells and B cells)
• myeloid stem cells give rise to all the other cellular elements
• blasts = precurser cells
• reticulocyte- last stage before RBC becomes erythrocyte, or mature RBC
• has just ejected nucleus, organelles ect
• has granules or ribosomes

• regulate differentiation and proliferation
• erythropoietin (EPO)
• produced by the kidneys
• checks fluids to make sure oxygen carrying carrying capacity is adequate, manages viscocity ect
• increase RBC precursor
• thrombopoietin (TPO)
• hormone from liver stimulates platelet formation
• cytokines - local hormones of bone marrow
• colony-stimlating factor (CSF) and interleukin stimulate WBC production

red blood cells

• structure, how it leads to function
• normal count

• contain hemoglobin 
• makes up 1/3 of cell's weight
• oxygen-carrying protein
• gives blood red color
• biconcave disk
• increases surface area/volume ratio
• flexible shape for narrow passages (capillaries)
• no nucleus or organelles beside membrane
• no organelles such as mitochondria because to produce ATP would use aerobic respiration .. which requires oxygen so it would be using up the oxygen its suppse to be delivering- not efficient 
• normal RBC count ≈ 5 million/drop
• male = 5.4 million/drop
• female = 4.8 million/drop 
• new RBCs enter circulation at 2 million/second

hemoglobin

[image]

• globin protein consisting of 4 polypeptide chains
• one heme attached to each polypeptide chain
• each heme contains an iron ion (Fe²⁺) that can combine reversibly with one oxygen molecule
• when oxygen is bound to the iron, it makes the RBC brighter in color
• if it releases oxygen it can pick up something else like CO₂

• most of the O₂is transported here
• transports 23% of total CO₂ waste from tissue cells to lungs for release
• most of the rest of CO₂transported via plasma
• transports nitric oxide and super nitric oxide helping to regulate BP
• iron ions pick up NO and SNO and transports it to and from lungs
• NO causing vasoconstriction is released in the lungs
• SNO causeing vasodilation is picked up in the lungs

• live only 120 days
• wear out from bending to fit through capillaries
• no repair possible due to lack of organelles
• worn out cells removed by fixed macrophages in spleen and liver 
• breakdown products recycled

• the main stimulus is hypoxia (lack of oxygen)
• after nucleus is ejected reticulocyte is formed
• orange in color
• traces of visible rough ER
• reticulocytes enter blood
• in 1-2 days, they reject remaining organelles to become mature RBC (erythrocyte)

feedback control of RBC production

[image]

• tissue hypoxia
• examples
• anemia
• RBC production < destruction
• high altitude (air has less O₂
• circulatory problems
• kidney response to hypoxia
• release EPO (erythropoetin)
• hormone that goes into circulation and 

• less numerous that RBCs
• 5,000 to 10,000 cells per drop of blood
• 1 WBC for every 700 RBC
• leukocytosis is a high white blood cell count
•  microbes, strenuous exercise, anesthesia or surgery
• leukopenia is low white blood cell count
• radiation, shock, chemotherapy
• only 2% of total WBC population is in circulating blood at any given time
• rest are in the tissues on patrol loooking for invaders

description, prevalence and function of:

• erythrocytes
• leukocytes
• granulocytes
• neutrophils
• eosinophils
• basophils
• agranulocytes
• monocytes
• lyphocytes
• platelets (thrombocytes)

erythrocytes

• anucleate, biconcave discs that are 1/3 hemoglobin
• 5,000-10,000/mm³
• transports O₂and CO₂
• destroys pathogenic microbes and parasites
• removes worn cells

Leukocytes

Granulocytes- twice the size of RBCs, cytoplasmic granules present

Neutrophils

• 2-5 lobe nucleus
• granules stain light purple in neutral stain
• 54-62% of WBCs
• phagocytizes small particles 

Eosinophils

• bilobed nucleus 
• granules stain red in acid stain
• 1-3% of WBCs
• kills parasites
• can phagocytize but not main mode of attack
• can eject mitochondrial DNA which combines with another secretion to form a physical barrier that kills bacteria
• first evidence for DNA as anti-microbial
• helps control inflammation and allergic reactions

Basophils

• bilobed nucleus
• granules stain blue in basic stain
• less than 1% of WBCs
• releases heparin and histamine

Agranulocytes- cytoplasmic granules absent

Monocytes

• 2-3 times larger than RBCs
• nucleus varies from spherical to lobed
• 3-9% of WBCs
• phagocytizes large particles

Lymphocytes

• slightly larger than RBCs 
• nucleus nearly fills cells
• 25-33% of WBCs
• provides immunity

Thrombocytes (platelets)

• cytoplasmic fragment
• 130,000-360,000/mm³
• helps control blood loss from broken vessels 

new research

• neutrophils or monocytes emigrate from the blood into the area
• they adhere to inside surface of capillaries by margination
• they enter the interstitial spaces by diapedesis and are guided by chemotaxis

complete blood count

differential WBC count

platelets

(what stimulates production/lifespan and removal)

• thrombopoietin stimulates myeloid stem cells to produce platelets
• platelets have a life span of only 5-9 days
• aged and dead platelets are removed by fixed macrophages in the spleen and liver 9

• disc-shaped, 2-4 micron cell fragment
• anucleate
• 150,000-400,000/drop of blood
• help stop blood loss from damaged vessels by forming platelet plug and promote clotting

• stoppage of bleeding in a quick and localized fashion when blood vessles are damaged
• prevents hemorrhage (loss of large amount of blood)
• methods utilized (in this order)
• vascular spasm
• platelet plug formation
• blood clotting (coagulation = formation of fibrin threads)

• damage to blood vessel stimulates pain receptors
• reflex contraction of smooth muscle of small blood vessels
• can reduce blood loss for several hours until other mechanisms can take over

*works for small vessels or arteriole only, large ones too large to pinch off, capillaries dont have smooth muscle only a thin layer of simple squamus epithelium 

• platelets store a lot of chemicals in granules needed for platelet plug formation
• alpha granules
• clotting factors
• platelet-derived growth factor
• dense granules

steps in the process 

1. platelet adhesion
• when platelet detects collagen fibers, starts the process
• stick to exposed collagen and underlying damaged endothelial cells in vessel wall
2. platelet release reaction
• activated by adhesion
• extend projections to make contact with each other
• release chemicals to activate others and decrease flow in damaged vessel
3. platelet aggregation
• stick together and form platelet plug
• plug reinforced by fibrin threads

• substances required for clotting: 
• Ca²⁺
• enzymes synthesized by liver cells
• substances released by platelets or damaged tissues
• clotting is a cascade of reactions in which each clotting factor activates the next in fixed sequence resulting in formation of fibrin threads
• prothrombinase and Ca²⁺ convert prothrombin→thrombin
• thrombin converts fibrinogen→fibrin threads

• prothrombinase is formed by either intrinsic of extrinsic pathway
• extrinsic
• seals outside blood vessel
• shorter pathway/ like sandbagging/ takes seconds
• intrinsic
• works to seal inside/repair pipe itself
• full pathway
• occurs in wall of blood vessel
• platelets damaged and release phospholipids
• takes minutes
• same result for both pathways- activation of fibrin threads from fibrinogen with asistence of calcium 
• prothrombinase and Ca²⁺ catalyze convertion of prothrombin→thrombin
• in presence of Ca²⁺, thrombin converts soluble fibrinofen to insoluble fibrin

• clot plugs ruptured area of blood vessel
• platelets pull on fibrin threads causing clot retraction
• edges of damaged vessel are pulled together
• fibroblasts and endothelial cells repair the blood vessel

• normal clotting requires adequate vitamin K
• fat soluble vitamin
• required for synthesis of 4 clotting factors by hepatocytes
• factors II (prothrombin), VII, IX and X
• produced by bacteria in large intestine

• fibrinolytic system dissolves small, inappropriate clots and clots located at site where repair has been completed
• fibrinolysis is dissolution of a clot
• inactive plasminogen is incorporated into the clot
• activation occurs because of factor XII and thrombin
• plasminogen becomes plasmin (fibrinolysin) which digests fibrin threads
• activation takes so long, the clot is no longer needed
• clot formation remains localized
• anticoagulants present in blood produced by mast cells

• thrombosis
• clot (thrombus) forming in unbroken blood vessel
• forms on rough inner lining of BV
• if blood flows too slowly (stasis) - allows clotting factors to build up locally and cause coagulation (gets bored and starts seeing more foreing objects)
• embolus
• clot, air bubble or fat in the blood (floating around)
• ex) the bends
• low dose aspirin blocks synthesis of thromboxane A2 and reduces inappropriate clot formation

• anticoagulant suppress/prevent blood clotting
• heparin
• administered during hemodialysis and surgery
• warfarin (coumadin)
• antagonist to vitamin K 
• blocks synthesis of clotting factors
• slower than heparin
• cons are that they will bleed much longer if they get a cut
• blood stored in blood banks treated with citrate phosphate dextrose that removes Ca²⁺
• thrombolytic agents injected to dissolve clots
• directly or indirectly activate plasminogen
• streptokinase or tissue plaminogen activator (TPA)

• antigens and antibodies
• agglutination- clumping of RBCs following transfusion 
• due to interaction of proteins on surfaces of RBCs (antigens) with certain antibodies carried in the plasma

blood types/groups

[image]

• type A 
• has A antigens on RBCs 
• has anti-B antibodies in the plasma
• type B
• has B antigens on RBCs
• has anti-A antibodies in the plasma
• type AB blood
• has both A and B antigens
• no antibodies in the plasma
• AB+ universal recipient
• type O blood
• has neither antigen
• both types of antibodies in plasma
• O- universal donor
• adverse transfusion reactions are avoided by preventing the mixing of blood that contains matching antigens and antibodies
• adverse reactions due to agglutination of RBCs

• antigen was discovered in blood of Rhesus monkey
• people with Rh agglutinogens on RBC surface are Rh⁺
• normal plasma contains no anti-Rh antibodies
• antibodies develop only in Rh- blood type and only with exposure to the antigen
• transfusion on positive blood
• during a pregnancy with a positive blood fetus

anemia: not enough RBCs

• symptoms
• oxygen-carrying capacity of blood is reduced
• fatigue, cold intolerance and paleness
• lack of O₂for ATP and heat production
• types of anemia
• iron-deficiency: lack of absorption or loss of iron
• pernicious: lack of intrinsic factor for B12 absorption
• hemmorrhagic: loss of RBCs due to bleeding (ulcer)
• hemolytic: defects in cell membranes cause rupture
• ex) sickle cell anemia
• thalassemia: hereditary deficiency

• inherited deficiency of clotting factors
• bleeding spontaneously or after minor trauma
• subcutaneous and intramuscular hemorrhaging
• nosebleeds, blood in urine, articular bleeding and pain
• various types due to missing factors
• treatment is transfusions of fresh plasma or concentrates of the missing clotting factor

• too many leukocytes (WBCs) or abnormal WBCs
• usually due to cancer

• ≈ 100,000km of blood vessels in the body
• would go around the world 2.5 times
• the heart creates enough pressure in the left ventricle to squirt 9.1 meters
• capillaries about 1/30th diameter of human hair
• takes 1 minute for blood cell to circulate around entire body

1. heart
• located in the mediastinum
2. right lung
3. aorta
4. sternum
5. muscle
6. left lung
7. esophagus
8. sixth thoracic vertebra

1. superior vena cava
2. base of heart
3. right border of heart
4. pleura
5. inferior surface of heart
6. diaphgram
7. arch of aorta
8. pulmonary trunk
9. left lung
10. left border of heart
11. apex of heart
12. right lung

*The heart has

• 2 surfaces: anterior and inferior 
• 2 borders: right and left

1. pericardium
2. heart wall
3. endocardium
4. trabeculae carneae
5. coronary blood vessels
6. myocardium (cardiac muscle)
7. visceral layer of serous pericardium (epicardium)
8. pericardial cavity
9. parietal layer of serous pericardium
10. fibrous pericardium
• dense irregular connective tissue
• protects and anchors the heart, prevents overstretching

serous pericardium

• thin, delicate membrane
• contains
• parietal layer (outer layer)
• pericardial cavity with pericardial fluid
• visceral layer (epicardium)

* epicardium = layer

*visceral pericardium = membrane 

• epicardium
• visceral layer of serous pericardium
• myocardium
• cardiac muscle layer 
• bulk of the heart
• endocardium
• chamber lining and valves

1. left common carotid artery
2. left subclavian artery
3. arch of aorta
4. descending aorta
5. left pulmonary artery
6. auricle of left atrium
7. left pulmonary veins
8. coronary sinus (in coronary sulcus)
9. left ventricle
10. posterior interventricular sulcus
11. brachiocephalic
12. superior vena cava
13. ascending aorta
14. right pulmonary veins
15. right atrium
16. right coronary artery
17. inferior vena cava
18. middle cardiac vein
19. right ventricle
20. left atrium
21. right pulmonary artery

• 4 chambers
• 2 upper atria
• 2 lower ventricles
• sulci- grooves on surface of heart containing coronary blood vessels and fat
• coronary sulcus
• encircles heart and marks boundary between atria and ventricles
• anterior intercentricular sulcus
• marks boundary between ventricles anteriorly
• posterior interventricular sulcus
• marks boundary between ventricles posteriorly

1. superior vena cava
2. right pulmonary artery
3. pulmonary semilunar valve
4. right pulmonary veins
5. opening of superior vena cava
6. fossa ovalis
7. right atrium
8. opening of coronary sinus
9. opening of inferior vena cava
10. tricuspid valve
11. right ventricle
12. inferior vena cava
13. left common carotid
14. left subclavian artery
15. brachiocephalic artery
16. arch of aorta
17. ligamentum anteriosum
18. left pulmonary artery
19. pulmonary trunk
20. left pulmonary veins
21. left atrium
22. aortic semilunar valve
23. bicuspid valve
24. chordae tendineae
25. left ventricle
26. interventricular septum
27. papillary muscle
28. trabeculae carneae
29. descending aorta

• thickness of myocardium varies according to the function of the chamber
• ventricle walls much thicker and stronger than atrial walls
• right ventricle supplies blood to the lungs (little flow resistance)
• left ventricle is thickest to supply systematic circulation 

fibrous skeleton of the heart

[image]

• dense CT rings surroud valves of the heart, merge with the interventricular septum
• support structure for heart valves
• insertion point for cardiac muschle bundles
• electrical insulator between atria and ventricles

• A-V valves open 
• allow blood to flow from atria → ventricles when atrial pressure > ventricular pressure
• A-V valves close 
• preventing backflow of blood into atria

• SL valves open upon ventricular contraction
• allow blood ot flow into pumonary trunk and aorta
• SL valves close upon ventricular relaxation
• prevents blood form returning to ventricles
• blood fills valve cusps→ tightly closing the SL valves

• stenosis is a narrowing of a heart vavle which restricts blood flow
• insufficiency or incompetence is a failure of a valve to close completely

• left coronary artery
• circumflex branch
• in coronary sulcus, supplies left atrium and left ventricle
• anterior interventricular (IV) artery
• supplies both ventricles
• right coronary artery
• marginal branch
• in coronary sulcus, supplies right ventricle

1. ascending aorta
2. pulmonary trunk
3. right conornary artery
4. right auricle
5. marginal branch
6. right ventricle
7. aortic arch
8. left coronary artery
9. left auricle
10. circumflex branch
11. anterior interventricular artery/branch
12. posterior interventricular artery/branch
13. left ventricle

• collect wastes from cardiac muscle
• drains into coronary sinus- large sinus on posterior surface of heart

1. superior vena cava
2. right auricle
3. small cardiac vein
4. anterior cardiac vein
5. middle cardiac vein
6. right ventricle
7. inferior vena cava
8. pulmonary trunk
9. left auricle
10. coronary sinus
11. great cardiac vein
12. left ventricle

1. aortic arch
2. ascending aorta
3. right coronary artery
4. atrial arteries
5. anterior cardiac veins
6. small cardiac vein
7. marginal artery
8. pulmonary trunk
9. left coronary artery
10. circumflex artery
11. anterior interventricular artery
12. great cardiac vein
13. great cardiac vein
14. circumfelx artery
15. posterior interventricular artry
16. posterior cardiac vein
17. middle cardiac vein
18. marginal artery
19. right coronary artery
20. small cardiac vein
21. coronary sinus

cardiac muscle histology

[image]

1. desmosomes
2. mitrochondrion
3. intercalated discs
4. opening of transverse tubule
5. gap junctions
6. sarcolemma
7. nucleus
8. cardiac muscle fiber

• striated muschle with branching fibers instead of elongated fibers in skeletal muscles
• gap juctions = passages where cells connect to other cells 
• allow for passage of solutes
• help the cells to stay NSYNC lol

1. nucleus
2. Z disc
3. M line
4. H zone
5. I band
6. A band
7. sarcomere
8. thick filament
9. thin filament
10. sarcoplasmic reticulum
11. mitochondrion
12. transverse tubule
13. sarcolemma

• reduced blood flow through coronary arteries may cause ischemia. Ischemia is often manifested through angina pectoris
• a complete obstruction of flow in a coronary artery may cause myocardial infarction
• tissue distal to the obstruction dies and is replaced by scar tissue
• while it was long thought that cardiac muscle lacked stem cells, recent studies suggest stem cells in the blood can migrate to the heart and differentiate into myocardial cells

• cardiac muscle cells are autorhythmic cells because they are self-excitable
• repeatedly generate spontaneous action potentials that then trigger heart contractions

• three major layers
• tunica interna
• simple squamus epithelium known as endothelium
• basement membrane
• internal elastic lamina
• tunica media
• circular smooth muscle and elastic fibers
• tunica externa
• elastic and collagen fibers

• the functional propertis of arteries are elasticity and contractility
• elasticity allows arteries to distend and recoil when receiving high pressure blood from the ventricles
• contractility allows arteries to increase or decrease lumen size
• two types of arteries
• elastic
• muscular

• large arteries with more elastic fibers and less smooth muscle 
• able to receive blood under pressure and propel it onward
• also called conducting arteries
• function as a pressure reservoir

• medium-sized arteries with more muscle than elastic fibers in tunica media
• capable of greater vasoconstriction and vasodilation to adjust rate of flow
• walls relatively thick
• called distributing arteries because they direct blood flow

arterioles

[image]

• through vasoconstriction and vasodilation arterioles regulate blood flow from arteries into capillaries and alter arterial blood pressure
• metarterioles form branches into capillary bed
• to bypass capillary bed, precapillary sphincters close and blood flows out of bed in thoroughfare channel
• vasomotion is intermittent contraction and relaxtion of sphincters that allow filling of capillary bed 5-10 times/min

• connect arterioles to venules
• found near every cell in the body but more extenzive in highly active tissue (muscle, liver, kidneys and brain)
• exchange of nutrients and wastes
• capillary walls are composed of only a single layer of cells (endothelium) and a basement membrane

types of capillaries

[image]

• continuous capillaries
• intercellular clefts are gpas between neighboring cells
• skeletal and smooth muscle, CT and lungs served by these
• fenestrated capillaries
• plasma membranes have many holes
• kidneys, small intestine, choroid plexuses (make cerebral spinal fluid) and endocrine glands
• sinusoids
• very large fenestrations
• incomplete basement membranes
• liver, bone marrow, spleen, anterior pituitary and parathyroid gland

• small veins collecting blood from capillaries
• tunica media contains onlya few smooth muscle cells and scattered fibroblasts
• very porous endothelium allows for escape of many phagocytic white blood cells

• proportionally thinner walls than same diameter artery
• tunica media less muscle
• lack external and internal elastic lamina
• valves are thin folds of tunica interna designed to prevent backflow

• increased sympathetic stimulation of the veins
• increased skeletal muscle activity
• the respiratory pump creates a pressure gradient in the chest cavity, drawing fluid toward the heart