3. Blood (1) Flashcards
1
Q
What is blood?
A
- Fluid
- circulates in vessels
- consists of:
- Water, electrolytes (HCO3-)
- Nutrients (glucose, lipids,
micronutrients) - Proteins (albumin, inactive
clotting factors & anticoagulants) - Hormones,
- Waste products (urea, uric acid,
bilirubin
2
Q
What is the “Cells”?
A
- red blood cells
- platelets
- white blood cells
3
Q
What are functions of the red blood cells?
A
4
Q
Polynuclear:
Mononuclear:
A
5
Q
How are red blood cells produced?
Embryo and Foetus:
A
Liver and spleen
6
Q
How are red blood cells produced?
Adult life: bone marrow
A
- Bone marrow: in all bones, but in particular
- flat bones (iliac bones, sternum, ribs, vertebrae)
- proximal portions of long bones (tibia, humerus, femur)
7
Q
What is haematopoiesis (blood cell synthesis)?
A
8
Q
- All blood cells are made in red bone marrow.
- All blood cells are derived from pluripotent haematopoietic stem cells, also called ________.
A
haemocytoblasts
9
Q
In addition to replicating themselves, pluripotent haematopoietic stems cells produce partially differentiated daughter cells that are common _______ progenitor cells or common lymphoid _______ cells.
A
myeloid
lymphoid
10
Q
What is the function of common lymphoid progenitor cells?
A
- Common lymphoid progenitor cells divide and differentiate to ultimately generate T lymphocytes and B lymphocytes, which are important in the “adaptive” immune system.
11
Q
What is the function of B lymphocytes?
A
B lymphocytes make antibodies, which are proteins that bind to pathogens, foreign proteins and damaged cells and proteins as part of the immune response.
12
Q
- Common myeloid progenitor cells divide and differentiate to produce precursor cells for generating red blood cells: (4)
A
(erythrocytes), granulocytes, monocytes and megakaryocytes.
13
Q
Granulocytes include:
A
neutrophils, basophils and eosinophils, which are important for fighting infections by different types of pathogens.
14
Q
Megakaryocytes give off cell particles, called platelets, which are important for blood _______ (clotting) in combination with clotting factors in the plasma.
A
coagulation
15
Q
Erythropoiesis: Development and differentiation of red
blood cells (7)
A
16
Q
What is the function of Haematopoietic stem cells?
A
Haematopoietic stem cells divide to replicate and they to form partially differentiated common myeloid precursor stem cells.
17
Q
What is the function common myeloid stem cells?
A
Common myeloid stem cells replicate and differentiate to form unipotent stem cells that start to make haemoglobin and can give rise only to erythrocytes
18
Q
Unipotent stem cells replicate and form _______, which continue to make haemoglobin.
A
proerythroblasts
19
Q
How do proerythroblasts replicate?
A
- Proerythroblasts replicate and form erythroblasts, which also make haemoglobin.
- Erythroblasts then expel their nucleus and organelles (mitochondria, endoplasmic reticulum, etc.) to form reticulocytes, which still contain some RNA
20
Q
How are reticulocytes released?
A
Reticulocytes are released from the bone marrow into the blood, where they mature into erythrocytes (mature red blood cells), which are disk-shaped and have
no RNA or DNA.
21
Q
- Cell replication requires DNA replication.
- DNA replication requires nitrogenous bases.
- The micronutrients, folate (folic acid) and vitamin B12, are required for ________ of the nitrogenous bases used to make DNA, especially thymidine
(dTTP). (What happens to blood cells if a person has a deficiency of folate or vitamin B12?) - Synthesis of haemoglobin requires the micronutrient, ______. (What happens to blood
cells if a person has a deficiency of iron?) - Erythrocytes die after ~____ days in the blood.
A
biosynthesis
iron
120
22
Q
- A 50-year-old man has had kidney disease for years of years and it getting worse.
- When he comes to the clinic, his skin is pale, he is out of breath and tires very easily.
- How could his kidney disease explain his symptoms?
A
…
23
Q
Regulation of Erythropoiesis (red blood cell synthesis)
If there are too few RBCs: (3)
A
- Too little oxygen delivery
- Decreased metabolism
- Tissue cell death
24
Q
If there are too many RBCs (polycythaemia): (3)
A
- Enough oxygen present, but
- Increased blood viscosity
- Decreased flow (blood clots and other problems)
25
How do we tell the bone marrow to increase or decrease the synthesis of RBCs?
RBC oxygen and erythropoietin
26
Regulation of red blood cell synthesis:
27
How does Erythropoietin?
* Erythropoietin is the main hormone that stimulates erythrocyte (red blood cell) production.
* Made in the KIDNEY (90%) and liver (10%).
28
What is hypoxia?
* Hypoxia of the kidneys stimulates erythropoietin production.
* EPO is produced in cells bordering renal arterioles that are immediately sensitive to O2 changes in RBCs.
29
* EPO is produced in cells bordering _____ _______ that are immediately sensitive to O2 changes in RBCs.
* Release of ____ from the kidney stops once tissue oxygenation is back to normal.
renal arterioles
EPO
30
* Increased EPO release can be elevated for long periods of time to sustain long periods of exposure to ______ (e.g. in high altitude).
* If erythropoietin cannot be produced: lower stimulation of erythrocyte production ______.
hypoxia
anaemia
31
Insufficient erythropoiesis results:
in anaemia
32
Factors that decrease tissue oxygen (cause hypoxia)
and stimulate the production of Erythropoietin (EPO): (4)
* Anaemia = below-normal O2-carrying capacity of
the blood, characterized by a low haematocrit and/or low haemoglobin.
* Poor blood flow: e.g. heart failure, low blood
pressure, haemorrhage.
* Pulmonary disease: decreased O2 entry from lung
to blood.
* High altitude: O2 in the air is decreased.
33
Whole blood allowed to stand or centrifuged separates into: (3)
* cellular components (at the bottom of the tube)
* leukocytes on top of erythrocytes
* plasma (on top of the tube).
34
Cellular component (mostly red blood cells) =
45-55% (in Johannesburg) of the whole blood sample volume
35
Percentage volume of RBCs in blood =
Haematocrit.
36
= _________ RBCs/litre of Blood (~5 million
million/l) (more in men than women)
(compare with ~5 x 109/litre WBCs= ~5
thousand million/l)
37
Erythrocytes: (4)
* No nucleus (cannot replicate)
* No organelles (no protein synthesis, no oxidative
metabolism)
* Enzymes are present for anaerobic glycolysis, pentose
phosphate pathway (anti-oxidant), converting CO2 to
H2CO3 (carbonic acid, carbonic anhydrase)
* Disk-like biconcave shape
38
* _______ disk shape provides a large surface area for O2 to diffuse into the cell.
* Shape enables O2 to diffuse rapidly to the whole cell.
* Very flexible “loose” membrane allows RBCs to ______ and squeezes through vessels less than 3 μm in diameter (RBC diameter = 7.8 μm)
* RBCs contain ________.
* 12 – 16 g/decilitre of blood (1/10 litre)
= 120 to 160 g/l
Biconcave
deform
haemoglobin
39
1 Haem + 1 globin polypeptide chain (alpha or beta) =
1 subunit of haemoglobin
40
1 molecule of haemoglobin contains 4 haemoglobin subunits
1 molecule of haemoglobin contains : (3)
-4 haems
-4 polypeptide chains
-4 Fe++
2 alpha chains + 2 beta chains haemoglobin A
41
What is the function of haemoglobin?
42
Erythrocyte and Haemoglobin Breakdown: (3)
* Lifespan of an erythrocyte ~120 days
* Membranes become fragile and break when erythrocytes go through small vessels in the spleen (3 μm vs. 8 μm of diameter).
* When the cells break, free haemoglobin is bound by a plasma protein, haptoglobin.
43
What happens when macrophages phagocytose haptoglobin-haemoglobin complex?
44
Where is bilirubin released? (4)
* Bilirubin is released into the blood
* Bilirubin is then transported to- and metabolized by- the liver and intestines.
* Plasma haptoglobin concentration decreases.
* Liver’s capacity to metabolise bilirubin is exceeded and bilirubin accumulates in blood and tissues skin and mucosa and eye conjunctivae become yellow (icteric) jaundice
45
What happens if there is excessive breakdown of RBCs?
to: (2)
plasma haptoglobin
plasma bilirubin
46
How does Haemoglobin (Hb) Bind Oxygen? (7)
How does Haemoglobin (Hb) Bind Oxygen? HAEM
* 98% of O2 in blood is bound to Hb
* 1 molecular oxygen (O2) binds to Fe2+ in each
haem group.
* 4 O2 + Hb --> Hb(O2)4
* Binding is non-covalent and reversible
* Fe2+ is not oxidised (to Fe3+) (methaemoglobin).
* O2 binds to Hb easily (tightly) in the pulmonary
capillaries (high [O2]).
* O2 is released easily in the capillaries of the
peripheral tissues (low [O2]).
47
When O2 is bound to Hb --->
When O2 dissociates from (leaves) Hb --->
* When O2 is bound to Hb blood appears red
(arteries)
* When O2 dissociates from (leaves) Hb blood
appears blueish (veins)
48
What is the process of cooperative bonding?
49
Cooperative Binding of Oxygen to Haemoglobin (Hb)
O2 concentration in tissues:
O2 concentration in lungs:
50
Other things that bind to Haemoglobin (Hb)
also affect Oxygen Binding Affinity: (3)
51
Allosteric effects on Haemoglobin Oxygen Binding:
52
Allosteric effects of Carbon Monoxide on Haemoglobin Oxygen Binding:
53
Other things that bind to Haemoglobin (Hb)
affect Oxygen Binding Affinity: CO and NO
54
What is anaemia?
Anaemia is a lower than normal O2-carrying capacity of the blood that is characterized by a low haematocrit and/or low haemoglobin concentration.
55
Signs and symptoms of anaemia:
56
Three Major Mechanisms of Anaemia:
* Decreased red blood cell (erythrocyte) replication
* Decreased haemoglobin synthesis
* Excessive loss of red blood cells (erythrocytes)
57
Haemoglobin concentration:
58
Haematocrit
* red blood cell volume as % of volume of whole
blood ----> ___
LOW
59
Mean Cell Volume (MCV)
* = ________ (%) x 10/RBC count (x1012/litre)
* = size (volume) of the red blood cell (in
femtolitres (fl), 1 fl = 10-15 litres)
* Normally 80 – 100 fl per cell.
* varies according to the type of _______
haematocrit
anaemia
60
Normocytic= _____
Microcytic=_____
Macrocytic= _____
Normocytic=Normal MCV
Microcytic=Low MCV
Macrocytic=High MC
61
Mean Cell Haemoglobin (MCH)
* Amount of haemoglobin in each cell
* = Haemoglobin (g/dL) x 10/RBC count
(x1012/l)
* = Hb/cell (in pg = 10-12 grams)
* varies according to the type of ______
aneamia
62
Mean Corpuscular Haemoglobin
Concentration (MCHC)
* Haemoglobin ________ inside RBCs
* = Haemoglobin (g/dl) x 100/haematocrit (%)
* = haemoglobin concentration per dL of red
blood cells (in g/dL)
* varies according to the type of anaemia
concentration
63
What is regenerative anaemia? (3)
64
What is non-regenerative anaemia? (2)
* When bone marrow cannot increase reticulocyte synthesis (i.e. when renal function, erythropoiesis or Hb synthesis is decreased) reticulocyte counts are normal or low.
* This is called a non-regenerative anaemia
65
Anaemia caused by decreased erythrocyte production
Peripheral:
kidneys produce insufficient erythropoietin
(EPO) (chronic renal disease)
66
Anaemia caused by decreased erythrocyte production
Central:
the bone marrow cannot produce cells even
when erythropoietin (EPO) is high
67
= Non-regenerative: decreased cell replication causes
decreased ________
reticulocytes
68
* Lifespan of erythrocytes: ____ days
* Lifespan of platelets: 11- 20 days
* Lifespan of white cells: 1- 4 days
120
69
* Blood cells need to be ________ constantly
* Cells must reproduce VERY rapidly
* Nucleotides (with bases A, C, G & T) are needed
* Nutrients are needed to synthesise nucleotides
(_____________)
replenished
(vitamin B12 and folate)
70
Peripheral causes of Decreased Red Cell Production:
71
Peripheral causes of Decreased Red Cell Production: What is the anaemia produced?
72
How does decreased Erythropoiesis due to B12/folate deficiency take place?
73
What type of anaemia is produced from B12 deficiency?
74
What happens in Vitamin B12 Deficiency & Pernicious Anaemia?
75
What type of anaemia is pernicious anaemia?
= Non-regenerative macrocytic anaemia
76
What is Folate/Folic acid Deficiency Anaemia? (2)
* Folate (vitamin B9) in green vegetables, fruits, liver
and meats (but destroyed by HEAT).
* Folate deficiency can be caused by malabsorption e.g.
alcoholism, GIT disease, pregnancy, cancer or
chemotherapy
77
What type of anaemia is Folate/Folic acid Deficiency Anaemia?
= non-regenerative macrocytic anaemia
78
Decreased Cell Division and Replication due to
Leukaemia or Toxins: (6)
79
Anaemia Caused by Decreased Haemoglobin
Synthesis: (3)
- Iron deficiency
- Anaemia of chronic disease
- Genetic: Thalassemia
= Non-regenerative
80
* If haemoglobin cannot be made, each erythrocyte will be smaller. (microcytic anaemia)
* This can happen in 3 circumstances:
81
Iron Deficiency & Anaemia of Chronic Disease: (3)
82
* Decreased haemoglobin in each red blood cell: (3)
83
* Iron, released by macrophages when they breakdown
haemoglobin or absorbed from food, is transported in them blood as transferrin. Iron is then transferred to bone marrow or stored in the liver as _____.
* In iron deficiency there is not enough iron stored in the body
* Ferritin (iron storage protein) is _____
* In anaemia of chronic inflammatory disorders, a protein made during chronic inflammation (hepcidin) prevents release of iron from macrophages and liver --> iron is sequestered (stuck) in macrophages and liver as ferritin ----> stored iron cannot be used by bone marrow to synthesize haemoglobin.
* Ferritin is _____.
ferritin
low
high
84
Iron Deficiency Anaemia: (2)
- Insufficient intake
global malnutrition or special diets (vegetarian/vegan).
- Excess loss
* chronic bleeding in the intestines (ulcer, cancer)
* heavy menses due to fibroids/coagulation disorders
85
What does iron anaemia deficiency lead to? (5)
86
1. Lack of erythropoietin, e.g. due to renal disease, causes decreased erythropoiesis, which results in a decreased number of reticulocytes and RBCs, with normal size and Hb content. ----> Anaemia is
normocytic, normochromic and non-regenerative.
87
Decreased ability to synthesise DNA due to folate or vitamin B12 deficiency ----> Anaemia is
macrocytic, hypo/normochromic and non-regenerative.
88
Decreased pluripotent haematopoietic stem cells due to leukaemia or fibrosis ---> Anaemia is
normocytic, normochromic and non-regenerative.
89
Decreased haemoglobin synthesis from decreased availability of iron or decreased globin protein synthesis ----> Anaemia is
microcytic, hypochromic and non-regenerative.
90
Excessive loss of RBCs:
* Haemorrhage (acute)
* Haemolysis
91
Increased EPO stimulates increased ________.
reticulocytes
92
Excessive Blood Loss: Haemorrhage & Bleeding:
* Blood loss -----> fewer RBCs in blood -----> lower O2 carrying capacity -----> tissue _______
* Hypoxia in kidneys stimulates ______ production
* Erythropoietin stimulates erythropoiesis -----> ↗ reticulocytes in the blood
* Acute heavy blood loss (haemorrhage) ----> increased __________ appear in the blood after 2-3 days
hypoxia
erythropoietin
reticulocytes
93
Chronic blood loss (intestinal bleeding, eg, ulcers or
cancer)
* Initially (the first 2-3 months) high ________ ---->
>2% reticulocytes in blood
* Prolonged loss of RBCs -----> loss of iron
* Chronic loss of iron (over several months) -----> depletes ____ stores ----> iron deficiency
* Iron deficiency -----> decreased ability to make ______ ----> iron deficiency anaemia (non-regenerative)
erythropoiesis
iron
RBCs
94
What is the process of Excessive RBC Destruction: Haemolysis?
95
What are the causes of haemolysis and haemolytic anaemia? Genetic disorders:
96
What are the causes of haemolysis and haemolytic anaemia? Infections:
97
What are the causes of haemolysis and haemolytic anaemia? Antibodies:
98
What are blood groups? (3)
99
* Blood group antigens are modified sugar molecules (α-N –acetylgalactosamine or α-D-galactose) that are attached or NOT to the surfaces of red blood cells (and other cells), depending on the ____ genes that the person inherits.
* OR
* Blood group antigens are proteins that are present or NOT in the membrane of red blood cells (not other cells) depending on _____ genes.
ABO
rhesus
100
What are ABO Blood Types? (4)
101
* The ABO gene (chromosome __) is an enzyme (glycosyltransferase) that attaches a ____ molecule to the cell surface
9
sugar
102
3 variants of the ABO gene:
103
Two copies/alleles of the ABO gene:
104
Group O, most common~ ___
Group A, 30- ___%
Group B, varies with _____ (8-25%)
Group AB : 3-5%
50%
40%
ethinicty
105
How do the anti-blood group antibodies work?
106
Peculiarity of Anti-ABO Blood Group Antibodies:
* Usually antibodies are made only after exposure to antigen.
* But, anti-A and anti-B antibodies are made in the first months of life.
* ______ intestinal bacteria have (sugar) molecules similar to A and B antigens.
* Bacteria stimulate development of __-lymphocytes that make anti-A and/or anti-B antibodies.
* If antigens are present on own cells = self, B-lymphocytes making the matching antibodies are ______.
* If antigens are NOT present on cells = NON-self, B-lymphocytes making the matching antibodies are _______ and antibodies continue to be made.
Symbiotic
B
destroyed
retained
107
What does this mean for blood transfusions?
108
What happens in a mismatched transfusion?
109
What happens in a mismatched transfusion?
Recipient's antibody recognition of foreign antigen causes a transfusion reaction: (2)
110
* Clumping of erythrocytes leads to mini
‘strokes’ (blocked capillaries) ---> disseminated intra-vascular _________
* Massive destruction of erythrocytes ---->
massive release of intracellular haemoglobin ----> renal toxicity -----> acute renal failure
* Antigen-Antibody reaction stimulates
cascades of pro-inflammatory messengers -----> “_____ ______” -----> fever
* -----> death or severe damage (stroke, renal
failure).
coagulation
cytokine storm
111
Why is the Rhesus blood group important? (6)
112
Mother Rh- and fetus Rh+
Rhesus Blood Group System:
113
2 variants of the Rhesus D gene:
114
115
* D is _______.
* Mother dd and father Dd ----> 50% chance foetus is ____
* 55% of Rh+ fathers are Dd, only 45% are DD = 100% chance foetus is Rh+
dominant
Rh+
116
What is the process of blood typing?
117
How do you verify blood compatibility? (2)
* Mixing red blood cells from potential donor with plasma from the
recipient.
* If no clumping ----> donor blood can be given to the recipient
118
Many other blood group systems
- tested before _________
- tested especially before organ and bone marrow
transplants to avoid _______
transfusions
rejection
119
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