Bio 2301 Human Physiology - Exam 3

Where do blood cells develop?

- Red bone marrow

- About 2 million new RBCs are produced every second

RBC development steps

- Hemosytoblast (occurs in red bone marrow)

- Reticulocyte (young RBC - red bone marrow)

- Erythrocyte (REC - occurs in blood stream)

Hematopoiesis

Blood cell formation

Erythropoiesis

Red blood cell formation

Function and types of white blood cells

- Function in phagocytosis, immunity, protection

- Types: neutrophils, eosinophils, basophils, monocytes, and lymphocytes

Function of platelets

Play a role in blood clotting

Function of RBCs

- Oxygen transport

What is the significance of a bioconcave disk shape of RBCs?

Allows for a high surface to volume ratio so oxygen and carbon dioxide can diffuse rapidly to and from the interior of the RBC

Function of erythropoietin

- A hormone made by the kidney that stimulates RBC production

- Released whenever pO2 is low (lung disease, heart disease, anemia, or high altitudes)

RBC average life in the circulation

- Lifespan of RBC: 120 days

- During their lifespan they carry oxygen

- As they approach the end of their lifespan, they become stiff and rigid and become stuck in small blood vessels - must be removed from blood

Removal of RBCs from the blood

- Done in the small capillaries of liver and spleen

- When RBCs get stuck in those capillaries, they are destroyed by phagocytic cells

Breakdown of RBCs

What happens when bilirubin accumulates?

- The person will turn yellow because bilirubin is a yellow-orange pigment

- Can happen when RBCs are being broken down too fast or if the bile can't get into the small intestine or with liver failure

Antigen

- on RBC membranes

- Like "cell name tags"

- Recognized by cells of the immune system so the immune system knows which RBC are "self" and which are "non-self"

Antibody

- Consists of antigens A & B and antibodies against A & B

- A & B antigens are codominant

- The antibodies are preformed, meaning that you have them even if you have never been exposed to foreign blood

- Whatever antigens you have is what blood type you are

- You have antibodies against whatever antigens you don't have

Four blood types in the ABO system

- Type AB: has A & B antigents on RBC and no antibodies

- Type A: has antigens on RBC and antibodies against B in plasma

- Type B: has antigens on RBC and antibodies against A in plasma

- Type O: has no antigens on RBC and antibodies against A & B

Rh System

- Involves a different antigen on the RBC membranes, the Rh antigen

- If someone has the antigen, they are Rh positive and they will not make the antibodies against Rh

- If someone does not have the antigen, they are Rh negative and they will make antibodies against Rh

Erythroblastosis fetalis

- A problem when you have an Rh negative mother pregnant with Rh positive baby

- During pregnancy, there is no mixing of mother's and baby's blood, however at the time of placental separation, some of the baby's blood can enter the mother's bloodstream

- The mother recognizes the RH antigens as foreign and fights against those RBCs by making antibodies against RH

- The next time a woman gets pregnant with an Rh positive baby, her antibodies will enter that baby's bloodstream and destroy the baby's RBCs - if that baby lives to be born, it will be very anemic and need a complete blood transfusion at birth

How do you prevent erythroblastosis fetalis?

RHoGAM injections given to Rh negative mothers during pregnancy?

What is hemostasis?

The stoppage of bleeding and consists of three processes: vasospasm, platelet plug formation, and blood clotting

Vasospasm

- Mechanism: the damaged blood vessel spasms down - caused by a reflex of the blood vessel and serotonin that is released by the damaged blood vessel

- Significance: decreases blood loss from that vessel - you get more vasospasm with increased damage to the vessel

Platelet plug formation steps of development

Damage to blood vessel -> collagen from deeper layers of the blood vessel is exposed -> platelets adhere to those sticky collagen fibers -> platelets release ADP and Thromboxane A2 and the damaged endothelial cells release von Willebrand's factor -> more platelets come to the area -> formation of a platelet plug that plugs up the hole

Limiting plug growth

- Nearby undamaged endothelial cells inhibit platelet adherence by release Prostacyclin (PGl2) and nitric oxide (NO)

- This makes sure the plug does expand onto the undamaged entothelium

What are the two pathways along which a clot is formed?

Intrinsic pathway and extrinsic pathways

What do both factors involve?

Calcium and clotting factors/proteins

Where are clotting factors made?

They are made by the liver and circulate in the plasma in inactive form

What coenzyme helps the liver make clotting factors?

Vitamin K

What happens when a person has liver failure?

They are not able to make those clotting factors and they will bleed excessively

What can act to prevent that liver from making clotting factors? What is an antidote?

- Rat poison (warfarin) and Coumadin (a blood thinner) prevent the liver

- Antidote for warfarin toxicity is vitamin K

What anticoagulants function to prevent clotting and how?

- EDTA and citrate function to prevent clottign by chelating calcium - they bind up the calcium in the blood so it is not present to cause clotting

The intrinsic pathway of clotting

- Forms a clot in 3-6 minutes

- Is initiated only when there is damage to the lining of the blood vessel wall

- Uses the clotting proteins XII, XI, IX, VIII, X, Thrombin, and Fibrin

The extrinsic pathway of clotting

- Forms a clot in 15 seconds

- Is initiated when there is damage to the blood vessel and tissue around it

- Uses clotting factors VII, X, Thrombin, Firbin, and Tissue Thromboplastin

What is fibrin

The clot itself

What is thrombin?

The enzyme right before the clot - if you have thrombin, you can form a clot

Clot development involves...

the polymerization of the fibrin to form a meshwork which traps blood cells within the clot

Clot retraction occurs and causes...

the cut edges of the vessel to be brought closer together, giving you a smaller hole to repair

What do platelets release and what does it stimulate

- Release PDGF (platelet derived growth factor)

- Stimulates the healing of the blood vessel wall

What happens once healing has occurred?

- TPA (Tissue Plasminogen Activator) is released from the healed endothelial cells and activates plasminogen

- Faxtor IIa and Thrombin also activate plasminogen

- Plasminogen becomes plasmin when it is active and the plasmin will digest the clot

Plaminogen is ___________ into the clot when the clot is made and the clot has a _________ way of getting rid of itself

- incorpoated

- built in

Why don't you want the clot around after you do not need it anymore?

- A piece of the clot can break off and start traveling in the blood stream, becoming an embolus

- These emboli can get stuck in small blood vessels, causing strokes, heart attacks, and pulmonary emboli

What happens with over-aggressive clot formation?

- Can cause strokes, heart attacks and pulmonary emboli

What else causes unwanted clot formation?

- Rough tissue inside the blood vessels

- The rough lining of the blood vessel with stimulate platelet plug formation and then clots will form

- Example: Atherosclerosis which causes cholesterol deposits in the arteries

- Blood pooling: the pooling of blood will activate clotting factors

How does aspirin prevent clot formation?

Inhibits thromboxane A2 therefore inhibiting the formation of the platelet plug

What substances does the body have that limit clot growth?

- Antithrombin III: present in the plasma, binds thrombin and inactivates it so thrombin cannot form clots elsewhere

- Herapin-Like Molecules on endothelial cells: increase the activity of antithrombin III

Boyle's Law

- States that pressure of a gas varies inversely with volume

- If volume goes up, pressure goes down

- It volume goes down, pressure goes up

Relevant pressures

- Atmospheric: 760mmHg at sea level

- Intrapulmonic: pressure in the alveoli and it changes with the phases of breathing but it always eventually equalizes with atmospheric pressure

- Intrapleural: pressure within the pleural cavity, it changes with the phases of breaking but is always less than intrapulmonic pressure

Muscles of inspiration

- Resting inspiration: diaphragm and external intercostals

- Deep inspiration: neck and back muscles

Volume and pressure changes during inspiration

Volume goes up, pressure goes down and air goes in

Muscles of expiration

- Resting expiration: no muscles needed - the external intercostals and diaphragm relax, causing decrease volume -> elastic recoil of the lungs increases pressure in lungs -> air goes out

- Forced expiration: abdominal muscles - these increase pressure in the abdomen which increases pressure in the chest and forces air out

Compliance

The ability to expand the lungs for inspiration

Consequences of decreased compliance

Decreased ability to inhale

Restricted airway diseases

- Cause decreased vital capacity and restrict the ability to expand the lungs, causing decreased compliance

- Examples: fibrosis (scar tissue in lungs), silicosis (talc or other substances in the lungs)

Other causes of decreased compliance

Anything that decreases the flexibility of the thoracic cage like a chest wrap that is too tight or something heavy on someone's cgest

What is the significance of surface tension in compliance?

- The tension at the air-water interface within the alveoli

- If the surface tension is not lowered, the work to breath would be too great - too hard to expand the alveoli - and you would not be able to breath in

What chemical is produced by the cells of the alveoil and what does it do?

- Surfactant is the chemical produced

- It decreases surface tension and therefore decreases the energy needed to expand the lungs

Do premature babies have surfactant?

No so they cannot breathe on their own

Airway resistance

Especially to air flowing out of the lungs

Consequences of increases resistance

Causes problems exhaling

Obstructive airway diseases

- Cause increased resistance and therefore people have difficulty breathing out

- Examples: asthma, chronic bronchitis, and emphysema

- Do not change vital capacity

Resting tidal volume

- The volume of air breathed in or out with each normal breath

- About 500 ml

Inspiratory reserve volume

- The extra amount of air you can breathe in after a normal breath

- About 3,000 ml

Expiratory reserve volume

- The extra amount of air you can breath out after a normal breath out

- About 1,500 ml

Vital capacity

- The total amount of exchangeable air

- = inspiratory volume + resting tidal volume + expiratory reserve volume

- About 5,000 ml

Residual volume

- The volume of air in the respiratory tract after you breath out all you can breath out

- This keeps the lungs open

- If you get "the air knocked out of you", this is what is lost and lungs can collapse

- About 1,000 ml

Total lung volume

- All the air the respiratory system can hold

- = vital capacity + residual volume

Inspiratory capacity

- The volume of air you can breath in

- Inspiratory reserve volume + tidal volume

Functional residual capacity

- The volume of air left in the respiratory system after a normal exhalation

- Expiratory reserve volume + residual volume

Dead space

- The volume of air in the part of the respiratory tract where gas exchange does not occur (the larynx, trachea, bronchi, most bronchioles, and any alveoli that aren't getting air)

What happens when dead space is increased?

- Resting tidal volume will be decreased because the same amount of air will fill the dead space and not much will get to the alveoil where gas exchange occurs

- Happens when someone is on a ventilator - tubing adds extra dead space

Diffusion

- Oxygen diffuses from the air in the alveolus into the blood in the pulmonary capillaries

- Carbon dioxide diffuses from the blood of the pulmonary capillaries into the air of the alveolus to be exhaled

Ventilation - perfusion coupling

- At any given time, not all of your alveoili are receiving air

- What you want is for the alveoil which are getting air (the ones being ventilated) to receive blood (to be perfused)

- If an alveolus is not ventilated you do not want it to be perfused

What happens if an alveolus is ventilated but not perfused?

The oxygen in the air has nowhere to go and is just breathed out (it is wasted)

What happens if an alveolus is not ventilated but perfused?

The blood coming to that alveolus won't get much oxygen and the blood leaving the lungs will be low in oxygen and high in carbon dioxide

General patterns of oxygen and carbon dioxide transport

- O2 is transported from the lungs to the tissues by arterial blood

- CO2 is transported from the tissues to the lungs by venous blood

Basic chemical structure of hemoglobin

- Made up of 4 polypeptide chains

- Each chain has a globin portino (made of amino acids) and a heme portion (a porphyrin ring containing iron)

Basic functions of hemoglobin

- Carries oxygen that bounds to the iron on the heme

- Carries CO2 that bounds to the globin portion

In what two ways is oxygen carried in the blood?

- Bound to hemoglobin - the molecule is then called oxyhemoglobin and this is the MAIN WAY to transport oxygen

- Dissolved in the plasma

Factors that lower hemoglobin's affinity for oxygen

- Low pH (lots of acid)

- High pCO2

- High temperature

- High DPG (made by RBCs during anaerobic metabolism)

- Since these lower hemoglobin's affinity for oxygen, hemoglobin gives up oxygen more readily - ensures that working tissues get the oxygen they need

Conditions at lungs and tissues

- At the lungs, there is high pO2 in the inhaled air and lower pO2 in the blood at the pulmonary capillaries - O2 will diffuses from the air into the blood

- At the tissues, there is a lower pO2 in the tissues than in the blood so O2 leaves the blood and enters the tissue cells

Myoglobin

- An oxygen binding protein that is found in skeletal muscle cells

- An extra way to hold oxygen there to be used by cells

Fetal hemogolbin

- Present in the fetus who is getting oxygen from its mother's blood rather than breathing

- Has a high affinity for oxygen so it can efficiently extract the oxygen from its mother's blood

In what three ways in carbon dioxide transported in the blood?

- Dissolved in the plasma

- Bound to hemoglobin - molecule is now called carbaminohemoglobin

- In the form of bicarbonate (the main way)

How much CO2 is transported by being dissolved in plasma

Only a small amount

Carbon dioxide bound to hemoglobin

- Bohr effect: when CO2 is high in the blood, it causes a decrease in pH

- Low pH causes an increase in oxygen unloading to tissues

How much CO2 is transported by being transported into bicarbonate?

The main way CO2 is transported in the blood

CO2 transport equation

CO2 + H20 <-> HzCO3 <-> H+ + HCO3-

Buffering hydrogen ions with hemoglobin

The H+ are picked up by the hemoglobin and thereby buffered

Reuction of the hemoglobin's affinity for oxygen by hydrogen ions

- Allows better oxygen unloading to the tissues

- High CO2 at the tissues allows the oxygen to get to the tissues - a working tissues will be producing a lot of CO2 and will need a lot of O2

Basics of equilibrium

- The CO2 transport equation is reversible and can go in either direction

- Whichever side of the equation has more reactant will push the equation to the other side - that is, if there is a lot of CO2, it will form a lot of bicarbonate and if there is a lot of H+ and bicarbonate, it will form a lot of CO2

Tissues: supply of CO2 drives equation of bicarbonate formation

- Bicarbonate is made inside the RBC and then it leaves the RB and enters the plasma, where it is carried

- At the tissues, CO2 is converted to bicarbonate

Lungs: exhaling CO2 pulls equation from bicarconate side toward CO2 formation

- CO2 leaves the blood and enters the alveoilar air and is exhaled

- At the lungs, the bicarbonate is converted back into CO2 and that CO2 goes out into exhaled air

Significant of hemoglobin binding

- CO2: comes from tissue cells and binds to the globin portion of hemoglobin - does not affect hemoglobin's ability to carry oxygen

- Hydrogen ions: from CO2, binds to hemoglobin and causes more O2 to be released to tissue cells

- Carbon monoxide: binds to the heme portion of hemoglobin (where O2 usually binds) - hemoglobin has a 210x greater affinity for carbon monoxide than for oxygen so just a little carbon monoxide can displace oxygen and cause the cells to suffocate

Respiratory chemoreceptors in the regulation of ventilation rate

- Location: in the CNS, carotic arteries, and the aortic arch

- Parameters monitored: pCO2, pH (H+), and pO2

- Response produced: decreased pO2, increased pCO2, or decreased pH (increased H+) will increased respiratory rate and vice versa will decrease respiratory rate

What are the rationale for the chemoreceptor responses?

Regulation of blood oxygen and blood pH

Relative significance of the three chemoreceptors

CO2 is the main chemical influence on breathing - you breath mainly to get rid of Co2

Altitude adaptation

- At high altitudes, oxygen is not so readily available

- Initial response is to increase respiratory rate

- Short term adaptation: increase RBCs produced because the kidneys will release more erthyropoietin which gives the blood the ability to carry more oxygen

- Long term adaptation: there will be increased capillaries, increased myoglobin, and increased number of mitochondia in cells

Exercise

- Causes increased respiratory rate

- Motor areas of the brain will cause muscles and will also send information to respiratory neurons to cause them to increase respiratory rate

- Chemoreceptors will respond to the decrease in pH (increase in H+) (lactic acid accumulation) to cause increased respiratory rate and increased depth of respiration - trying to blow off those H+ in the form of CO2

Definition of pH

The measure of H+ concentration

A low pH means ____ and a high pH means _____

- Low = lots of H+

- High = less H+

Acid

An H+ donor - has a lot of H+ and therefore a low pH