Destruction of RBC

 NADPH serves the RBC

– Maintaining the pliability of the cell
membrane
– Maintaining membrane transport
of ions
– Keeping the iron in Hb in Fe++
rather than Fe+++ state

Oct 9, 2020 Blood 1

 Destruction of RBC
 As the cells become old
– Metabolic processes become
progressively less active
 Membrane become fragile
 Ruptures easily especially

– During RBC passage through spleen

Oct 9, 2020 Blood 2

 Destruction of RBC
 When RBC membrane rapture
– Released Hb is phagocytosed by
macrophages RES
 Hb is split into
– Globin and haeme
 Haeme ring is opened to give
– Free iron
• Transported in blood by Transferrin
– Porphyrin protion

Oct 9, 2020 Blood 3

 Destruction of RBC
 Porphyrin portion of the haeme
– Converted into biverdin
– Biliverdin is further converted into
bilirubin
 Bilirubin
is gradually released from the
macrophages into plasma
– Free bilirubin is bound to plasma proteins

Oct 9, 2020 Blood 4

 Anaemia
 Anaemia means deficiency of RBCs
which can be due to
– Too rapid loss of RBCs
– Slow production of RBCs
 Types
– Blood loss anaemia
– Aplastic anaemia
– Magaloblastic anaemia
– Haemolytic anaemia
Oct 9, 2020 Blood 5
 Blood Loss Anaema
 After haemorrhage
– Body replaces plasma within 1 to 3 days
 This leaves low conc of RBC in plasma

 RBC can return to normal within 3 to 6 weeks

 In chronic blood loss

– An individual cannot absorb iron rapidly enough
to cope with HB synthesis
 RBC are formed with little Hb

– They are pale (Hypochromia)

– They are small in size (Microcytosis)
• Microcytic hypochromic anaemia
Oct 9, 2020 Blood 6
 Aplastic anaemia
 Due to lack of function of bone
marrow
– Exposure to gamma radiation,
certain industrial chemicals,
excessive X-rays, certain drugs

Oct 9, 2020 Blood 7

 Megaloblastic anaemia
 Due to lack or deficiency of vitamin
B12, folic acid
– Required for DNA synthesis
 Deficiency of these leads to
– Slow reproduction of erythroblasts in
bone marrow
 They become large with odd shapes
– Megaloblasts (have fragile membrane)
easily rapture
• Development of anaemia
• Megaloblastic anaemia
Oct 9, 2020 Blood 8
 Haemolytic anaemia
 In this condition normal number
of RBC is being formed but
– They have abnormalities which
make their membrane fragile
 They rapture easily as they go through
the capillaries
– Hence life span greatly reduced
• Anaemia develops

Oct 9, 2020 Blood 9

 Haemolytic anaemia
 Examples
– Hereditary spherocytosis
 RBCare small and have spherical
shape
– They are easily ruptured as they pass
through the spleen pulp
• Haemolysis

Oct 9, 2020 Blood 10

 Haemolytic anaemia
 Sickle cell anaemia
 RBC contain abnormal type of HB known as
Hb-s
  Chain of Hb are abnormal
– Valine is substituted for glutamic acid at
one point
 When it is exposed to low O2
– It precipitates into long crystal inside the
RBC
– Which elongate the cell into a sickle shape
– Fragile membrane
• Breakdown of RBC –(Haemolysis)

Oct 9, 2020 Blood 11

 Erythroblastosis
foetalis
 Affect a child of
– Rh negative mother married to Rh
positive man
 Rh positive RBC in foetus
– Attacked by antibodies from Rh negative
mother
 Antibodies make the cell fragile
 Rapture
– Haemolysis
– Anaemia

Oct 9, 2020 Blood 12

 Anaemia

Adaptive Changes in
Anaemia

13 Anaemia Oct 9, 2020

 Anaemia
 Deficiency of haemoglobin
 Red blood cells may be deficient

– In number
– In haemoglobin
– In both number & Hb

Oct 9, 2020 Anaemia 14

 Anaemia
 There is fall in all three RBC
indices
– Red cell count
– Haematocrit
– Blood Hb level

Oct 9, 2020 Anaemia 15

 Anaemia
 The Hb level
– Most often used to diagnose or
exclude anaemia in patients
 Normal values
– 15 gm/100 ml of blood
– Slightly higher in men than in
women

Oct 9, 2020 Anaemia 16

 Anaemia
 Wide variation
 Values below

– 11 gm/100 ml in women
– 12 gm/100 ml in men
 Suggestive of anaemia

Oct 9, 2020 Anaemia 17

 Anaemia
 Hgb level also depend on
– Plasma volume
 Factors that  plasma vol
  Hgb level
 Factors that  plasma vol
  Hgb level

Oct 9, 2020 Anaemia 18

 Binding of O2 to Hgb
 Under ideal conditions
– 1 gm of Hgb
 Combine with 1.39 ml O2
 In the normal human body
– 1 gm of Hgb combine with 1.34 to 1.36 ml
of O2 (Huffner’s number)
 Small fraction of Hgb is in an inactive form

Oct 9, 2020 Anaemia 19

 O2 Carrying Capacity of
Blood
 Maximum amount of O2 that can be
bound by the Hgb
– 1 gm of Hgb combine with 1.34 ml O2
– Amount of Hgb available = 15 gm Hgb/100
ml of blood
 15*1.34 = 20.1 ml O2 / 100 ml blood
 This is the O2 carrying capacity of blood

Oct 9, 2020 Anaemia 20

 Oxygen Flux
 Total amount of O2 transported
by blood per minute
– O2 flux = C.O*(arterial O2 content)
– O2 flux = 5000*(20/100)
– O2 flux = 1000 ml O2 /min

Oct 9, 2020 Anaemia 21

 Oxygen Flux
 Under normal condition
– 250 ml of O2 is utilized (25% of O2 flux)
 Thus circulating blood loses 25% of its Oxygen
 Venous blood is approx 75% saturated with O2
 The 75% of the un-extracted O2 forms “reserve”

Oct 9, 2020 Anaemia 22

 Oxygen Flux
 Determined by
– Cardiac output
– Hgb concentration
– Saturation with O2

Oct 9, 2020 Anaemia 23

 Effects of Anaemia
Oxygen Flux vs Hgb concentration

1200

1000
ml O2/CO (5L/min)

800

600
O2 Flux
reserve
400

200

0
16 15 14 13 12 11 10 9 8 7 6 5
Hgb gm/100ml

Oct 9, 2020 Anaemia 24

 Effects of Anaemia
 Line “A”
O2 Carrying Capacity per CO – Normal level of
1200 tissue O2
1000 extraction 250
800 C ml/min
ml O2/CO(5ml/min)

600

400
B  Line “B”
A
200 – Twice the
0
16 15 14 13 12 11 10 9 8 7 6 5
normal level
Hb gm/100 ml

Oct 9, 2020 Anaemia 25

 Effects of Anaemia
 Line “C”
O2 Carrying Capacity per CO – Three times
1200 normal level
1000

800 C
ml O2/CO(5ml/min)

600
B
400
A
200

0
16 15 14 13 12 11 10 9 8 7 6 5
Hb gm/100 ml

Oct 9, 2020 Anaemia 26

 PO2 vs Quantity of O2 Bound
to Hb
97% sat ; 19.4 ml O2

20
 Thus under normal
O2 content ( ml O /100 ml blood)

conditions
5 mls
16
– When Hgb = 15
gm/dL
– About 5 ml O2/100
2

75% sat, 14.4 ml

12 O2
ml blood are
transported from
8 lungs to tissue

4
[V%]

20 40 60 80 100
PO2 (mm Hg)
Oct 9, 2020 Anaemia 27
 PO2 vs Quantity of O2 Bound
to Hb
97% sat ; 19.4 ml O2

20
 In anaemia Hgb
O2 content ( ml O /100 ml blood)

5 mls
= 7.5 gm/dL
16 – Less than 5 ml
O2/100 ml
2

12 blood will be
< 5 mls
transported
8
from lungs to
tissue
4
[V%]

20 40 60 80 100
PO2 (mm Hg)
Oct 9, 2020 Anaemia 28
 Effects of Anaemia
 For a given fall in O2 partial
pressure
– Anaemic blood release less O2 to
tissues than normal blood
 Effects of anaemia
– Arises from the lack of O2 to tissues
& the compensatory changes to
hypoxia

Oct 9, 2020 Anaemia 29

 Effects of Anaemia
 Anaemia usually develops slowly
– Give time for compensation
 Thus a patient with severe
anaemia
– May have few complaints
 The  circulating Hgb
– Accounts for the pallor of anaemia

Oct 9, 2020 Anaemia 30

 Tissue Hypoxia
 Tends to be slight in mild
anaemia
– Covered by the compensatory
changes
 In severe anaemia
– Tissue hypoxia  markedly

Oct 9, 2020 Anaemia 31

 Skeletal Muscles
 Functions is impaired
  PO leads to anaerobic
2
metabolism
– Accumulation of lactic acid
 Muscle weakness & fatigue
 Stimulation of respiration

 Breathlessness during exertion

Oct 9, 2020 Anaemia 32

 Heart
 In severe anaemia
– Heart muscle hypoxia
 Angina pain
– Cardiac muscle weakness
 Reduced exercise tolerance
– Breathlessness on exertion
– Heart failure

Oct 9, 2020 Anaemia 33

 The Brain
  Arterial O2 content
– Renders the brain more sensitive to
any reduction of blood flow
 Light headedness
 Fainting attacks

 Lethargy

 Headaches

Oct 9, 2020 Anaemia 34

 Peripheral Nerves
 Hypoxia of peripheral nerves
– Tingling sensations
 Paraesthesia

Oct 9, 2020 Anaemia 35

 GIT
 Hypoxia of GIT
– Loss of appetite
– Abdominal discomfort

Oct 9, 2020 Anaemia 36

 Liver Hypoxia
 Impaired liver functions

Oct 9, 2020 Anaemia 37

 Compensatory
Mechanisms
 In anaemia there is
  O2 carrying capacity
  In O2 delivery to the tissues
 The body compensates for this by
  In O2 extraction by tissue
– Peripheral vasodilatation
  In cardiac output

Oct 9, 2020 Anaemia 38

 Compensatory
Mechanisms
 Tissue hypoxia causes
– Release of erythropoeitin by the
kidneys
  stimulation of erythropoiesis by
the bone marrow

Oct 9, 2020 Anaemia 39

 Decrease Hgb-o2 Affinity
 Hypoxia
 O2 extraction of anaemic blood by
tissues
  Conc of deoxy-Hgb in RBC
– Stimulates production of 2:3DPG
– Shifts Hgb-o2 dissociation curve to
the right

Oct 9, 2020 Anaemia 40

 Decrease Hgb-o2 Affinity
 This allows for more O2 off-
loading at the tissues

Oct 9, 2020 Anaemia 41

 Peripheral
Vasodilatation
 Hypoxia in tissues causes
– Vasodilatation of resistance vessels
 Leads to  in TPR
 The  BP initiates reflex
mechanisms
  Sympathetic discharge

Oct 9, 2020 Anaemia 42

 Peripheral
Vasodilatation
 The increase in sympathetics
leads to increase in
– HR
– Force of contraction of heart
– Myocardial contractility
 All this tend to cause
–  in cardiac output

Oct 9, 2020 Anaemia 43

 Peripheral
Vasodilatation
 The pulse pressure increases
– The  force of contraction of the
heart
 Raises the SBP
– The  in TPR causes a  in DBP
 Hence the pulse pressure rises

Oct 9, 2020 Anaemia 44

 Peripheral
Vasodilatation
 The  in HR &  pulse pressure
– Known as hyper-dynamic
circulatory states
 Haematocrit is decreased
– This decreases blood viscosity

Oct 9, 2020 Anaemia 45

 Peripheral
Vasodilatation
 Hence the  in CO &  viscosity
  Velocity of blood flow
  Turbulence
– Leads to abnormal heart sound
 Heart murmurs

Oct 9, 2020 Anaemia 46

 Stress
 Any type of stress
– Infection, illness
– Produce more severe effects
 Body is working at
– A disadvantage due to hypoxia
 Sudden blood loss
– Dangerous in anaemia
 During child birth

Oct 9, 2020 Anaemia 47