lecture 13,14- Flashcards
The functions of the mamallian respiratory system ?
- Provides O2 to blood and eliminate CO2 from blood
- regulates blood H+ conc
- Forms speech sounds
- defends against inhaled microbes
- Traps & dissolves blood clots arising from systemic veins
highly branched airways=alveoli->site of gas exchange
What are the 2 circuits that are in circulatory system ?
- Pulmonary circulation:right ventricle->lungs->left atrium
- Systemic Circulation:left ventricle ->peripheral organs & tissues->right atrium
delivery of nutrients & O2 to tissues& removal of CO2
BC suspended in plasma
Where are RBC produced ?
prod in red bone marrow -destroyed in spleen & liver
-hormone : erythopoietin
formation requires iron,folic acid,vitamin B12
What is anaemia ?
decrease in the ability of blood to carry O2
1. A decrease in total no of RBC
2. lower conc of Hb per RBC
3. or combo of both
4. bone marrow failure
5.
ron storage in body: 50% (of total body iron)
is in haemoglobin, 25% in other haem/heme-
containing proteins (e.g. cytochromes) in
cells, and 25% in liver as ferritin (protein
RBC and the transport of respiratory gases ?
blood within pulmonary capillaries seperated from air
by thin barrier
Total alveolar SA is huge–>rapid exchange of large quantities of O2 & CO2 by diffusion
Blood transport of respiratory gases ?
Vertebrates use haemoglobin in RBCs; high concentration
of haemoglobin (in mammalian blood) allows each volume
of blood to carry 50-60x more O2..!
Haemoglobin the respiratory pigment ?
Quaternary structure
composed of more than 1 polypeptide chain together
Vertebrate Hb has 4 polpeptide globin subunits
2 a,2b subunits
each heme= 1 Fe2+ atom reversibly bind to1 O2
What is Hb positive cooperativity ?
ability to combine with O2 depends on PO2
High PO2 –>can carry 4 O2 max
Low PO2 –>some O2 is released from Hb
displayed by hB binding dissociation curve
Sigmodial :low PO2 ,only 1 subunitbinds to 1 O2–>conformational change ->altering quaternary structure–>increasing affinity of other subunits
easier for 2nd O2 to bind
some extra info on Hb and CO ?
combine with other ligands -H+,CO2
allosteric ligands/modulators
CO binds with 240 fold higher affinity than O2 competing with the latter–>preventing O2 being transported -toxic /deadly at high conc
Total amount of O2 trnasported by blood Hb
What is normal partial pressure of gas in air and body ?
Alveolar PO2 is lower than atmosphere PO2 because of net diffusion of alveolar O2 into lung capillaries
Alveolar Po2 and PCO2 determine the sytemic arterial PO2 , PCO2
Hb abilty for loading & unloading O2 ?
High PO2 in lungs vs Low PO2 in venous blood–>Hb binds (loads O2)
Low PO2 in tissues cappilaries vs High PO2 in arterial blood
Loading:oxygenation of Hb
Unloading :deoxygenation
How does Hb load O2 in the lungs ?
Plasma & RBC enetering (venous blood) have PO2 of 40mmHg
O2 diffuses into blood–>RBC
O2 binds Hb removing O2 from dissolved solution –> lowers the plasma PO2
thuis gradient is maintained unitl Hb is 100% saturated
Exiting blood :100mmHg
O2 bound to Hb does not contribute directly
to blood PO2; only dissolved O2 does
What is Hbs loading plateau O2 ?
loading plate provides protection
If alveolar PO2 falls to 60 mmHg
even a moderate limitation of lung
function still allows for significant Hb saturation!
Hb:O2 unloading in tissues ?
Plasma and RBC entering tissue capillaries =PO2 -100 mmHg
O2 unloaded into blood-then diffuses into tissue/cells
plasma PO2 falls-only 25% O2 is unloaded
exiting blood PO2 -40mHg
O2 unloading in general ?
cells still can get more O2 whenever they increase activity
Exercising muscle -consumes more O2 –>lowering intracellular & interstitial PO2 –>increasing blood-to-cell ratio
-increased rate of O2 diffusion from blood into cells=decrease in RBC PO2 casues additional unloading
if tissue PO2 fall below 40mmHg-reserve O2 released
Myoglobin and properties ?
muscle cells -own O2 binding aka myoglobin
found in skeletal & cardiac muscles
consists of 1 polypeptide chain with 1 heme
can bind to 1 O2 with very high affinity
1. facilitates diffusion of O2 in muscle cell
2. provides O2 reserve
Myoglobin as a reserve of O2 how does it work ?
during exercise=high metabolic demand & interruptions in supply of O2 :
tissue PO2 drops and Hb cant supply more O2 -myoglobin then release its bound to O2
Myoglobin abindant in muscles of diving muscles
During vigorous exercise, blood PO2 is lower than at rest → blood passes through lungs
faster:↓ time of gas exchange
Human Hb vs Human Mb O2 eqm curves ?
Myo=hyperbolic O2 eqm curve contains 1O2 binding sites per molecules ->no coperativity
Is Hbs affinity for O2 variable ?
yes its dependent on
1. CHemical composition of Hb
2. presence of 2,3-bisphosphoglyceric acid
3. pH,CO2,H+
4. Temperature
What is the chemical composition of Hb ?
Fetal Hb:8 weeks after conception consists of 2 a,2y globin subunits
higher affinity for O2 than adult Hb
Adult Hb :consists of 2a2b globin subunits
How does living at higher altitiudes affect Hb ?
Llamas-live at >5000 metres above seaw level
higher affinity for O2 than fetal/adult Hb
Hb becomes saturated at much lower PO2
Llama vs Human ?
Llama
* Hb with high affinity for O2
* binding curve shifted to left
* saturated occurs at lower PO2 values
* tissues can operate at lower PO2
Human
* Hb never 100% saturated due to low environmental PO2
* binding curve shifted to right
* More O2 is unloaded in tissues
What does the presence of 2,3-bisphosphoglyceric acid do ?
reversibly bind to Hb –>alosteric conformational change
–>reduces Hb affinity for O2
High levels of 2,3-DPG in mature RBCs as they
rely on glycolysis (there are no mitochondria):
↑ [2,3-DPG] enhances O2 unloading.
What is the Bohr effect ?
O2 affintiy decreases as pH decreases so curve shifts to right.
What effect does CO2 have on binding to globins ?
CO2 bind to globin causing allosteric conformational change –>reduces Hb affinity for O2–>increased O2 unloading in tissues
How does temp effect O2 affinity ?
an increase = decrease in O2 affinity
shifts their O2 binding curves to the right
O2 affinity of Hb is (often) inversely dependent on the temperature.
How does the blood transport CO2 ?
3 modes of transport of CO2
1. 5-10% dissolved in physical solution-plasma -cytosol of RBC
2. 20-30% reversibly bound to A groups on Hb not containing O2 :carbaminohaemoglobin
3. 60-70% converted =bicarbonate ions in cappilarie endothlial cells and primarily in RBC
What is the blood transport of CO2 :as HCO3- ?
A-rate limiting step
* catalysed by carbonic anhydrase
* in capillary endothelium & primarily RBC
* prod carbonic acid
* B-Rapid dissociation
* no enzyme involved
* dissociates into proton (H+) and bicarbonate ions
* HCO3-=transported into plasma in exchanhe for CL-=chloride shift
The transport of CO2 in blood ?
RBC membrane transporter exchanges for 1 bicarbonate ion for 1 chloride -chloride shift=maintaining electroneutrailty
deoxyhaemoglobin =higher affinity for H+ so it binds most of H+–>only small amount of free H+ in plasma
CO2 is highly soluble; readily diffuses through cell membranes
The transport of CO2 to the lungs ?
reversed reaction
Venous blood PCO2 >alveolar PCO2 =net CO2 diffusion into lungs –>drives reaction above the right
HHb releases H+, picks up O2 → the H+ reacts with HCO3- → enzymatic conversion to H2CO3 → dissociates: CO2 into alveoli
What are the mechnics of breathing ?
Visceral pleura covers lungs
pleural layers are seperated/filled by intrapleural fluid –>intrapleural pressure changes cause the lungsglide over thoracic wall during breathing
How does the control of breathing respiration work ?
breathing = autonomic rythmical process of inhalation follwed bty expiration
-Diaphragm and intercostal muscles contrct in respons to efferent activity from phrenic and interocostle nerves
asic respiratory rythm is generated in brainstem -meulla oblangata
-involes 2 groups of neurons :dorsal,ventral respiratory system
reflexes -can influence breathing pattern
What are the nerve patterns invloved in breathig ?
neurons medulla establish the respiratory rythm this info is transmitted by descending motor neurons
How is breathing regulated ?
lack of O2 stimulates hyperoxia stimulating respiration but strongest one is increase in CO2 (hypercapnia)
he body uses this feedback info (from chemoreceptors) to then match the breathing rate to the metabolic demand(s)
What are peripheral cheoreceptors ?
include carotid & aortic bodies:
carotid bodies have predominant roles in responding to changes in PO2 of arterial blood
afferents of CB increase AP charges as PaO2 falls below 50-60mmHg
In humans, the carotid bodies are/contain the only receptors/sensors able to elicit a ventilatory response to hypoxia.
