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103 theme 2 > Red blood cells > Flashcards

Red blood cells Flashcards

1
Q

how is oxygen moved in circulation

A

cooperativity and allosteric effect (more O2 bound in lungs and deposited in tissue)

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2
Q

how is oxygen carried in blood

A

poorly soluble in plasma - normal arterial blood flow carries 70x more O2 on haemoglobin than plasma

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3
Q

what is a key feature of haemoglobin binding to oxygen

A

must be weak enough to be reversible (mechanisms at muscles to reduce affinity)
cooperativity and right shifting of binding curve

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4
Q

what makes up the majority of RBCs

A

95% dry weight is haemoglobin

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5
Q

what is the structure of haemoglobin

A

each subunit has a ham group (616 Da) and and a large globin peptide (17000 Da)
Allosteric properties = cooperativity

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6
Q

what is a ham group

A

each haemoglobin and myoglobin has 1 ham group (carries O2)

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7
Q

what is the structure of a haem

A

porphyrin ring, rigid, 2D, highly coloured due to electron sharing
conjugated to iron ion (ferrous aka Fe2+)

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8
Q

how do haemoglobin’s 4 sub units interact

A

cooperativity
each sub unit has 1 oxygen molecule on its haem
each sub unit influences its 3 neighbours
O2 binding increases affinity leading to more binding and the same for release

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9
Q

what is the structure of haemoglobin

A

healthy adults HbA (2 a and 2 B subunits) aka maternal Hb
Foetal HbF (2 a and 2 g sub units)
adults have 1% HbF (binds to oxygen more strongly than HbA)

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10
Q

How does CO2 and H+ affect binding to Hb

A

Bohr Effect
Increased CO2 decreases affinity for oxygen (decreases blood pH via carbonic anhydrase)
CO2 and H+ bind to different parts of Hb than O2

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11
Q

How is CO2 transported in blood

A

10% dissolved
22% carbamino
68% as HCO3-

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12
Q

how is CO2 transported as carbamino

A

CO2 + Hb-NH2 <=> Hb-NH-COOH

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13
Q

how is CO2 transported as HCO3-

A

CO2 in, CO2 + H20 <=> H2CO3 <=> H+ + HCO3-, Cl- exchange (chloride shift) via band 3 protein

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14
Q

what is chloride shift

A

more chloride in venous blood than arterial

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15
Q

how does oxygen binding compare between myoglobin and haemoglobin

A

myoglobin - hyperbolic

haemoglobin - sigmoidal

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16
Q

what causes a rightward shift in oxygen affinity (decrease)

A

CO2 H+ Cl- 2,3-DPG (diphosphoglycerate) and muscle activity

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17
Q

how does 2,3 DPG lower oxygen affinity

A

binds to Hb
found in erythrocytes at 5mM
tiny molecule compared to Hb
HbF has a lower affinity than HbA so has a higher affinity for oxygen

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18
Q

how do oxygen saturation curves compare for material and foetal Hb

A

Myoglobin exponential
HbF sigmoidal (higher than HbA)
HbA sigmoidal

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19
Q

how does oxygen concentration vary in active muscles

A

O2 low, CO2 high, blood slightly acidic, temp high, myoglobin
as blood runs along capillary O2 leaves Hb, CO2 and H+ bind (RHS shift of oxygen saturation)
HCO3- leaves Plasma and Cl- enters

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20
Q

what is breathing controlled by

A

O2, CO2 and H+

plasma O2 must drop precipitously before respiration drive increases

21
Q

what is the main driver to increase respiration rate

A

H+ in CSF (H+ in blood is slow into CSF but CO2 quicker so can make HCO3- and H+)
CO2 response same as H+ (blood based, signal from carotid arch)

22
Q

what detects the increase of H+ in the CSF

A

medullary receptors sample from interstitial and CSF fluid

23
Q

what is the structure of erythrocytes

A

definite/ mature

biconcave disc, red when oxygenated, anucleate, no organelles, contains Hb

24
Q

what is the function of erythrocytes

A

bag of Hb to transport CO2 and O2
survive for 120 days
very flexible (fold and stack in blood vessels)

25
Q

how many erythrocytes are there

A

per um of blood they are the most numerous (5 million compared to 9000 leukocytes and 7000 platelets)

26
Q

what is haematocrit/ PCV

A

40-52% MALES and 36-48% FEMALES (amount in blood)

13-17 g/dl MALES and 12-16 g/dl FEMALES

27
Q

what is the mean cell Hb (MCH)

A

27-34 pg

28
Q

what is the mean corpuscular volume (MCV)

A

80-100 fL

29
Q

Where does erythrogenesis occur

A

after birth - bone marrow only
after 20 y/o membranous bones only
in embryo - liver, spleen, lymph nodes, yolk sac

30
Q

how does erythropoiesis occur

A

haematopoetic stem cell to burst forming unit erythroid to colony forming unit erythroid to erythroblasts to reticulocytes to erythrocytes
up to R in bone marrow
B to Eblasts is erythropoietin dependant
Eblasts to R is iron dependant

31
Q

what is erythropoietin

A

A cytokine/ hormone to drive erythropoiesis

made in kidney (response to hypoxia)

32
Q

how can erythropoietin be used medically

A

used to stimulate erythropoiesis (severe risks of severe target effects)
performance enhancing drugs for athletes

33
Q

what are reticulocytes

A 
RBC precursor (before complete extrusion of nucleus and organelles)
2 days in blood then definitive RBC
34
Q

how can reticulocyte be used as a diagnostic tool for anaemia

A

indicate bone marrow activity
high in haemolytic anaemias (homeostatic response)
low when erythropoiesis is low
machine counts and detects those with low basophilic material (eg DNA) in them

35
Q

what is methamoglobinaemia

A

Hb cannot transport O2

Fe in Hb is oxidised (Fe3+) instead of ferrous (Fe2+)

36
Q

what causes methamoglobinaemia

A

due to congenital globin mutations (HbM), hereditary decrease of NADH, toxic substances

37
Q

what causes CO poisoning

A

CO displaces O2 from Hb (same bind site as affinity is 250x stronger so low levels can displace more 02)
PO2 blood dissolved in blood normal
lethal

38
Q

what are the symptoms of CO poisoning

A

bright red blood, brain affected 1st = disorientation

39
Q

how is CO poisoning treated

A

95% oxygen/5% carbon dioxide (drives Hb to T configuration)

allows for CO to be displaced

40
Q

what is polycythaemia

A

increase number of RBCs therefore viscosity of blood so clogs blood vessels

41
Q

what are the types of polycythaemia

A

physiologic - high altitude
Polycythaemia vera - neoplasm, often asymptomatic, risk of thrombotic events, no cure so treat with venesection (all ages but increases with it, possibly genetic)

42
Q

what is iron required for

A

to produce RBCs, 65% of all iron in adults is in RBC Hb

43
Q

where is Fe stored

A

stored intracellularly as ferritin and haemosidesin (30%)

stored in reticulo endothelial system (liver, spleen, RBCs, bone marrow, macrophages and monocytes)

44
Q

what causes anaemia

A

deplete in all stores
only a small % of dietary iron absorbed
lose 1mg a day (more in pregnancy, menstruation and peptic ulcer)

45
Q

what is vitamin B12 and folic acid used for

A

important for rapidly dividing tissue (essential for DNA thymidine)
nuclear maturation fails (RBCs, skin, gametogenesis)
leads to fragile cells

46
Q

what causes vitamin b12 and folic acid deficiency

A

diet, malabsorption, lack of utilisation

eg vegan, pernicious anaemia, pregnancy, haemolytic anaemia, lymphoma, old age, institutions, famine

47
Q

how can vitamin b12 and folic acid deficiency be treated

A

with vitamins

oral folic acid or intramuscular hydroxocobalamin

48
Q

what is iron deficiency

A

hypo chromic microcytic anaemia

cells keep dividing but cannot fill up with Hb

49
Q

what is vitamin b12 and folic acid deficiency

A

megaloblastic anaemia
pernicious anaemia
cells keep filling up with Hb but cannot divide fast enough

103 theme 2 (7 decks)

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