M103 T2 L1 Flashcards
What is oxygen’s blood solubility like?
it’s poorly soluble
only a small amount is directly dissolved in the water of the plasma
Can pO2 be normal in a patient with hypoxia?
yes - bc there is no Hb to carry oxygen
What is the equation for respiration in muscle tissue?
C6H12O6 + 6O2 = 6CO2 + 6H2O + 36 ATP
What is the equation for anaerobic glycolysi?
C6H12O6 = 2 lactate + 2ATP
What percentage of the dry weight of an RBC is Hb?
95%
How many daltons is a haem group and a peptide in Hb?
small haem group - 616 Da
large globin peptide - 17,000 Da
What is the structure of haem like?
rigid, 2D and highly coloured porphyrin ring
How does co-operativity affect how affinity for additional uptake of o2 into Hb?
the allosteric effect means each subunit influences its 3 neighbours - it increases their affinity for O2 increases due to shape change
What types of Hb do adults have?
HbA - 99%
HbF - 1%
Which two factors affect Hb affinity for O2 and why?
increased blood CO2 and decreased blood pH
these are conditions in hard working muscles and allows Hb to lose affinity for O2 and offload it into the tissues
How does the carbolic anhydrase reaction affect blood pH?
it increases co2 blood levels
so there is a decreases in blood pH
What three modes are used to transport co2 in the blood?
10% dissolved
22% as carbamino
68% as HCO3-
What happens during chloride shift?
a co2 mlc (in deoxy muscle) enters Hb, and reacts to make an acid and carbonates which are removed from Hb in exchange for Cl-
What happens to chloride shift when the deoxygenated blood reaches the lungs?
it reverses - H+ reforms into co2 and carbonate, the latter re-enters the Hb mlc in exchange for the removal of Cl-
What is the normal pO2 of the lungs?
100 mmHg
What are the graph shapes of myoglobin and Hb?
Hb - sigmoidal
myoglobin - hyperbolic
An increase in which molecules causes a Hb dissociation curve to rightward - shift?
co2, pH and Cl-
2,3-DPG
How does 2,3-DPG cause rightward-shift?
it binds to Hb, lowering its affinity for O2
How does HbF react to 2,3-DPG compared to maternal Hb?
HbF has a lower affinity for 2,3-DPG compared to maternal Hb
HbF therefore has a higher affinity for o2 instead
Explain the graph shape of myoglobin
has very high affinity; small amounts of oxygen just immediately fill up the myoglobin until it’s nearly totally full. There’s very little change after a certain level
Since normal Hb has a lower o2 affinity than myoglobin and HbF, how is it still effective?
a normal Hb mlc will be less avid to the o2 - will give away some of the oxygen. If that o2 just sits there, the Hb will go into EQL with the o2 concentration
However, if the Hb releases the o2 and it is then hoovered up by the myoglobin or by maternal haemoglobin, the Hb tries to get into EQL.
there’s very little oxygen in the plasma nearby because every time the Hb releases an oxygen, that oxygen is hoovered up out of the plasma and onto another bound to another molecule, either to the higher affinity, foetal haemoglobin or myoglobin.
What are the conditions in active muscles (during exercise)?
O2 is low, CO2 is high
Blood is slightly acidic due to co2 and lactic acid
Temperature is higher
There is myoglobin (left-shifted saturation vs Hb)
What happens to the different molecules in active muscles (during exercise)?
O2 leaves the Hb due to cooperativity
CO2 and H+ bind to Hb – shifts Hb saturation curve to the right
HCO3- leaves RBC and goes into the plasma plasma
Cl- leaves the plasma and the enters RBC (Cl- shift)
What is the main drive to increase the respiratory rate in normal adults and how is it generated?
acid in the cerebrospinal fluid
H+ in the blood is slow to get into the CSF because its charged and can’t get past the cell membrane, but CO2 gas can get into the CSF
once there it reacts through the enzyme carbonic anhydrase to make carbonic acid & H+
the increased pH is detected, indicates presence of co2, not enough o2 and increases breathing rate
Which molecule triggers an increased respiratory rate?
H+
low 02 = high co2
high co2 is detected by H+ in the CSF
How is blood H+ detected
signal from the carotid arch
How does the blood control breathing?
medullary receptors - they sample the acid from the interstitial and CSF fluid
What are the dimensions of an rbc?
How long does an rbc survive for?
7x2 microns
4 months
What is the function of erythrocytes?
Bag of Hb to transport O2 and CO2
Very flexible – fold and stack in blood vessels
How many WBCs and RBCs are there in the body?
RBC - 5M
WBC - 9000
How do we work out the haematocrit of a blood sample?
centrifuge the blood sample
what % of the cells are more dense
plasma is less dense, is pushed up to the top
blood cells pushed to the bottom
can tell what % of the total amount of fluid is actually pure cellular matter
Which parts of the body does erythropoiesis occur during embryogenesis?
(LYSL)
Lymph nodes
Yolk sac
Spleen
Liver
What are the four stages of development for stem cells?
Multipotent stem cells
Multipotent progenitor cells
Lineage-committed progenitor cells (commitment)
Mature cells (terminal differentiation)
Which cell type do myeloblasts develop from and what cells can they turn into? (B’N’EM)
originates from a common myeloid progenitor
basophil
neutrophil
eoisonophil
monocyte
What are the different stages of erythropoiesis? (HB,CERE)
Hematoepoietic stem cell BFU-E CFU-E Erythroblasts Reticulocytes Erythrocytes (RBCs)
How are reticulocyte counts used?
as a diagnostic tool in anaemia
What three things have the potential to cause methaemoglobinaemia?
Congenital globin mutations (Hb M)
Hereditary decrease of NADH
Toxic substances leading to the oxidation of Fe2+
What happens during CO poisoning?
Hb has an affinity for CO 250x that of its affinity for CO, so low levels of CO still completely displace O2
the pO2 remains normal, but Hb is not carrying oxygen (which is the main form of transport for O2 in the body as opposed to being dissolved in the blood
the blood turns bright red)
the brain is affected first - disorientation
What are the proportions of the air mixture treatment for CO poisoning?
95% oxygen - tries to displace or bind to any vacated spots on the Hb that the CO2 makes available
5% co2 - makes Hb less avid for the CO; helps to temporarily knock off the CO
How is polycythaemia vera treated?
venesection
How is iron stored in the body and by what proportions?
65% - Hb’s
30% - intracellularly as Ferritin & Haemosiderin
Where is iron stored in the reticulo-endothelial system?
Messy BLM
Macrophages/monocytes Erythrocytes Spleen Liver Bone Marrow
Why are vitamin B12 and folic acid important for rapidly dividing tissue?
they are essential for forming thymidine in DNA
if thymidine was not generated, would cause nuclear maturation to fail
so any cell type making cells quickly is very sensitive to vitamin B12 and folic acid deficiencies
What is megaloblastic (macrocytic) anaemia caused by?
deficiency / malabsorption of vit B12 and folic acid
increased utilization of vit B12 and folic acid
poor diet
What three things can cause increased utilization of vitamin B12 and folic acid?
Pregnancy
haemolytic anaemia
lymphoma
How is a vitamin B12 or folic acid deficiency treated?
the correct vitamin
Oral folic acid
Intramuscular hydroxocobalamin (B12)
What is oxygen bound to in the blood?
70x more is bound to Hb rather than the water in the blood
What are the stages by which the process of chloride shift occurs?
there’s lots of co2 mlcs present near the muscle tissue area which enters Hb mlcs
Co2 + h2o (+ carbonic anhydrase) = carbonic acid
decomposes into a proton and carbonate
the proton binds to Hb
the carbonate mlcs can accumulate in the cell which is bad
band 3 allows them to leave the cell in exchange for a chloride mlc
co2 near respiring muscle tissue bind to Hb
What is the role of band 3 in chloride shift?
it allows carbonate mlcs accumulating in Hb mlcs to leave in exchange for Cl-
What are the stages by which the process of chloride shift reversal occurs in the lungs?
far less co2
the Hb gives off the proton
the carbonate in the blood re-enters the rbc and swaps for chloride
chloride goes back into the blood
carbonic acid is regenerated and breaks down into its reactants of co2 and water
the co2 leaves the lungs
What is the role of 2,3-DPG?
allows oxygen release at tissue sistes
stabilises deoxyHb by allosteric binding
What do reticulocyte counts indicate?
that the bone marrow is activite and producing
What do high reticulocyte counts indicate?
haemolytic anaemias (homeostatic response)
What do low reticulocyte counts indicate?
something wrong with the bone marrow activity
How are reticulocyte counts taken?
a machine counts cells
it detects those with basophilic material in them
it calculates the % of cells that have reticulocytes
