Blood & Body Fluids Facts Flashcards
1
Q
Where do thrombin and vWf come from in the platelet adhesion step of platelet plug formation in haemostasis?
A
Thrombin: coagulation cascade (feedback)
vWf: megakaryocytes, endothelial cells, platelets
2
Q
What are the components of tenase?
A
VIIIa, IXa, Ca++
3
Q
How does Protein C, and its cofactor Protein S, prevent unnecessary coagulation?
A
Target Va and VIIIa to prevent clot formation (Va: forms prothrombinase; VIIIa: forms tenase)
4
Q
Total Transcellular fluid volume in typical adult human
A
negligible
5
Q
How are thromboxane A and prostacyclin (PGI2) synthesized? (main enzymes and intermediates)
A
From Phospholipids
Via phospholipase
To Prostaglantin H2 (PGH2)
To thromboxane A (damaged cells) or prostacyclin (intact cells)
6
Q
Describe the characteristics of the Intrinsic Pathway of blood coagulation & clot formation in haemostasis.
A
Ongoing during tissue regeneration
Uses components that are in the blood, or have precursors in the blood
7
Q
Name the 7 types of plasma proteins
A
Albumin Lipoproteins Glycoproteins Coagulation Factors Immunoglobins Complements Hormones
8
Q
How does low tissue O2 affect erythropoiesis?
A
signals to kidney to incr. EPO release, which stimulates erythropoiesis, increasing tissue O2
9
Q
What role does prothrombinase play in the Common Pathway of blood coagulation & clot formation in haemostasis?
A
Activates Prothrombin -> Thrombin
10
Q
Protein content level of ICF
A
High
11
Q
What effect does ADP release have on cells adjacent to an injured site in a blood vessel?
A
Causes release of prostacyclin (prostaglandin inhibiting platelet aggregation) and NO (vasodilator)
12
Q
Which factor targets Ca++ to prevent unnecessary coagulation?
A
Ca++ chelators
13
Q
Why does haematopoietic activity of femur & tibia bone marrow fall off sharply during childhood?
A
Bones need the density for growth; pass duties to bones that grow less
14
Q
What type of coagulation defect causes a defiency in prothrombin, VII, IX, X?
A
Vitamin K deficiency
15
Q
What role does plasmin play in haemostasis?
A
Fibrinolysis:
Stable fibrin -> soluble fragments
16
Q
What causes haemophilia?
A
Inherited
17
Q
Describe platelet adhesion during platelet plug formation in haemostasis.
A
- Glycoproteins constitutively expressed on endothelial and subendothelial cells
- Adhesion factor (thrombin, integrin, vWf) release by subendothelial cells
=> Platelets bind exposed collagen & each other
18
Q
What are the three biological phases of haemostasis?
A
- Initiation - Extrinsic pathway makes thrombin
- Amplification - Thrombin action: platelet activation, ^ prothrombinase activity, ^ tenase formation
- Propagation - Distal sites enhance tenase formation
19
Q
What is involved in the platelet aggregation step of platelet plug formation in haemostasis?
A
Platelet activation promotes aggregation; ADP & fibrinogen key to forming unstable platelet plug
20
Q
What are the components of prothrombinase?
A
Va, Xa, Ca++
21
Q
Haemostasis is an integrated system. What causes Haemostasis?
A
Platelet plug formation
Clot formation
22
Q
Which physical factor prevents unnecessary coagulation, and how?
A
Blood vessel integrity: -ve glycocalyx prevents -ve platelet adhesion
23
Q
Which factor targets IXa (only) to prevent unnecessary coagulation?
A
alpha-Protease inhibitor
24
Q
Which bones’ marrow play a key role in haematopoiesis as people age?
A
Vertebrae, ribs, sternum, pelvis
25
How do heparin and heparan sulphate prevent unnecessary coagulation in vivo?
Stimulate AT III (antithrombin III)
26
What happens to fibrinogen in the Common Pathway of blood coagulation & clot formation in haemostasis?
Hydrolyzed by thrombin to fibrin monomers and fibrinopeptides
Spontaneously polymeryzes to fibrin polymers
27
Which clotting factors are not produced sufficiently when there is a Vitamin K deficiency?
prothrombin, VII, IX, X
28
Which factor targets the TF.VIIa.Ca++ complex to prevent unnecessary coagulation?
Tissue factor pathway inhibitor (TFPI)
29
Major anion(s) in ECF: ISF
Cl-
30
What type of stem cells do pluripotent stem cells become if they are going to become thrombocyte?
Myeloid
31
Types of Granulocytes
Basophil
Neutrophil
Eosinophil
32
What happens to monocytes once they mature?
They enter the reticuloendothelial system:
- enter tissue and stays (becomes "fixed macrophage")
- signal
- breaks off (becomes "mobile macrophage")
33
What role does XIIIa play in the Common Pathway of blood coagulation & clot formation in haemostasis?
Stabilizes cross-links between fibrin polymers in the clot
34
In which pathways of Haematopoiesis is Erythropoietin involved?
Myeloid Stem Cell growth into Erythrocytes & Thrombocytes
35
Which factors do PAI1 and PAI2 act on?
t-PA, u-PA
36
What results from a IX deficiency?
Type B haemophilia (coagulation defect)
37
Total body fluid volume in normal adult human
42L
38
What role does TF play in the Extrinsic Pathway of blood coagulation & clot formation in haemostasis?
Binds and non-proteolytically activates VII;
| Acts with VIIa and Ca++ to convert X->Xa (proteolytically)
39
Which factor increases blood flow & prevents platelet aggregation/adhesion/activation & causes vasodilation to prevent unnecessary coagulation?
Endothelial PGI2 (prostacyclin)
40
How does alpha-Protease Inhibitor prevent unnecessary coagulation?
Targets IXa (forms Tenase)
41
Name the 6 main regulators of erythropoiesis
1. Tissue O2 levels
2. EPO
3. Cytokines (GM-CSF, IL-3)
4. Iron & copper
5. Folic acid & Vitamin B12
6. Sex steroids
42
What are the 4 events that occur during formation of a platelet plug in haemostasis?
("4 PAs")
a. Platelet Adhesion
b. Platelet Activation
c. Platelet Aggregation
d. Primary arrest of bleeding
43
Typical erythrocyte life span, and reason
120 days; can't synthesize protein & hemoglobin gets oxidized
44
What happens to fibrin polymers in the Common Pathway of blood coagulation & clot formation in haemostasis?
They are stabilized with cross-linkages, catalyzed by XIIIa
45
What happens to iron in erythrocytes?
Recycled: Macrophage breaks down erythrocyte and release Fe2+ back to plasma to be re-oxidized by Caeruloplasmin...
46
Haemostasis is an integrated system. What causes Clot formation?
Coagulation cascade
| Platelet adhesion/activation/aggregation
47
What do platelets release from the alpha granules during the platelet activation step of platelet plug formation in haemostasis?
Thromboxane A (for platelet aggregation)
factor V (clotting factor)
fibrinogen (for platelet aggregation)
vWf (promotes platelet adhesion)
48
What does a macrophage break haemoglobin down into, and what happens to those components?
- Globin -> amino acids; recycled
- Iron -> back to blood & transferrin; recycled
- Haem -> bilirubin -> in plasma -> albumin transports to liver -> bile -> secrete into intestine; excreted
49
What role do negative charges on activated platelets play in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?
Activate XII -> XIIa (slowly)
50
Total Plasma volume in typical adult human
3L
51
How does EPO affect erythropoiesis?
Prohibits BFU-E, CFU-E apoptosis (particularly CFU-E)
52
What are the components of the complex that activates X in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis? Does it have a name?
VIIIa, IXa, Ca++
| Name: Tenase
53
How is blood volume calculated (from known plasma volume)?
1. Use centrifugation to calculate % haematocrit, % plasma
| 2. V_blood = V_plasma / %plasma
54
Describe the Intrinsic Pathway of blood coagulation & clot formation in haemostasis.
- Slow conversion of XII->XIIa by contact with negative charges on activated platelets; cofactor: High Molecular Weight Kininogen (HMWK)
- XIIa feedsback to activation: stimulates prekallikrein->kallikrein, kallikrein proteolytically converts XII->XIIa
- XIIa.HMWK converts XI->XIa.HMWK
- XIa.HMWK converts IX->IXa
- ----
- (separately) vWf releases VIII
- thrombin converts VIII->VIIIa
- ----
- VIIIa.IXa.Ca++ ("tenase") converts X->Xa
55
Name the four roles of thrombin in haemostasis.
1. enhance platelet aggregation
2. Hydrolyze fibrinogen -> fibrin monomers & fibrinopeptides
3. Convert XIII -> XIIIa
4. Feedback (+) to increase production of VIIIa (-> tenase), Va (-> prothrombinase)
56
Major anion(s) in ECF: plasma
Cl-
57
Generally describe the process of haem synthesis
Porphyrins are synthesized/transformed in the mitochondria & cytoplasm, and eventually bind Fe2+ in the mitochondria to form haem
58
Shape of erythrocytes, and reason
Deformable biconcave disk; high SA:volume ratio for gas exchange, deformable to fit through capillaries
59
What is involved with the Humoral Substance Release portion of Vasoconstriction in haemostasis?
Serotonin (vasoconstrictor) is released by platelets or as a result of coagulation
60
Two main compartments of body fluids in humans & %
ICF (67%)
| ECF (33%)
61
What is involved in the Platelet Activation step of platelet plug formation in haemostasis?
- Platelets form pseudopodia
- Platelets release materials in dense granules (Ca++, ATP, serotonin, **ADP**)
- Platelets release materials in alpha granules (**thromboxane A**, factor V, fibrinogen, vWf)
** are linked
62
Which organs are hematopoietic, and when?
Yolk sac: early fetal development
Liver/spleen: mid-fetal development
Bone marrow: begins in mid-fetal development (4mo), decreases quickly in tibia & femur; decreases slowly in vertebrae/ribs/sternum/pelvis
63
2 main functions of blood & body fluids
Transport, Protection
64
What does bone marrow contain that allows it to be haematopoietic?
Pluripotent stem cells - can become erythrocytes, leukocytes, or thrombocytes
65
How does Endothelial NO prevent unnecessary coagulation?
Prevents platelet adhesion & aggregation
| Vasodilator
66
Protein content level of ECF: plasma
medium
67
What two compounds act as vasodilators to prevent unnecessary coagulation in intact blood vessels?
1. Endothelial PGI2 (prostacyclin)
| 2. Endothelial NO
68
What type of stem cells do pluripotent stem cells become if they are going to become monocytes?
Myeloid
69
How does GM-CSF/IL-3 affect erythropoiesis?
Promote erythrocyte development from precursors
70
Blood components
```
Plasma
Formed Elements
RBCs (Erythrocytes)
WBCs (Leukocytes)
Platelets (Thrombocytes)
```
71
What happens to mature erythrocytes (after forming from reticulocytes)?
Released from bone marrow, mature in 1-2 days
72
Name the three types of glycoproteins in the plasma
Transferrin
Haptoglobins
Caeruloplasmin
73
Describe the general process of erythrocyte breakdown by the reticuloendothelial system
Mobile macrophage takes up erythrocyte & breaks down membrane and haemoglobin
74
What is PAI-2 and what does it do?
Placental Plasminogen Activator Inhibitor; prevents plasminogen -> plasmin
75
What processes are involved in blood coagulation & clot formation in haemostasis?
Extrinsic Pathway, Intrinsic Pathway, Common Pathway
76
Name three Ca++ chelators
Oxalate, EDTA, Citrate
77
Which factor targets Va and VIIa to prevent unnecessary coagulation?
Protein C and its cofactor, Protein S
78
Transport pathway for nutrients in body fluids
Capillaries -> Interstitial fluid -> ICF
79
Describe the Storage step of iron metabolism
Excess iron is incorporated into ferritin, which is stored in the liver
80
Erythrocytes: nucleus?
no
81
What roles does XIIa.HMWK play in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?
Feedback on prekallikrein -> kallikrein, to make more XIIa.HMWK
Activate XI -> XIa.HMWK
82
What are the two events that occur during Vasoconstriction in haemostasis?
1. Local contraction
| 2. Humoral substance release
83
How do iron and copper affect erythropoiesis?
Iron helps form haem, copper helps caeruloplasmin oxidize Fe2+ -> Fe3+
84
Characteristics of Reticulocyte
Loses nucleus
| Only a few ribosomes & Golgi remnants left in cytoplasm
85
Which plasma proteins are involved with maintaining osmotic pressure?
Albumin
86
What type of stem cells do pluripotent stem cells become if they are going to become Lymphocyte?
Lymphoid
87
How does a clot form in haemostasis?
Fibrin lattice traps erythrocytes, leukocytes
88
Name 2 characteristics of erythrocytes related to CO2 transport
High [carbonic anhydrase] to convert CO2 -> HCO3-
| High anion permeability to allow Cl-, HCO3- exchange
89
Total ICF volume in typical adult human
28L
90
Describe thrombocytes, in terms of shape, nucleus, and membrane
Disk-shaped, but can changed w/ pseudopodia
No nucleus
Have "fuzzy" glycocalyx (negatively charged)
91
Roles of blood & body fluids in transport (5)
"RENCH"
Respiration (O2, CO2)
Excretion (waste to kidneys, intestines, lungs)
Nutrients (from gut to tissues; between organs)
Communication (hormones)
Homeostasis (water & control hormones)
92
What role does VIIa play in the Extrinsic Pathway of blood coagulation & clot formation in haemostasis?
Combines with TF, Ca++ to convert X->Xa
93
What are the attendant ions for Na+, and where are they used?
Cl-, HCO3-; in ECF
94
What do platelets release from the dense granules during the activation step of platelet plug formation in haemostasis?
Ca++, ADP, ATP, serotonin
95
Types of Leukocytes
```
Lympocytes
Granulocytes
Basophil
Neutrophil
Eosinophil
Monocytes
```
96
Describe the structure of haemoglobin
4 polypeptide (globin) chains: 2 alpha, 2 ß
Each globin chain holds 1 haem molecule in the middle (4 haem total)
Each haem molecule has 1 Fe2+ ion in the center, which binds 1 molecule O2 (4 O2 total)
97
Which factors are involved with the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?
```
vWf
VIIIa
kallikrein (prekallikrein)
XIIa.HMWK
XIa.HMWK
IXa
Ca++
```
98
Function of albumin in plasma
Maintain oncotic pressure, bind/transport drugs & other molecules
99
Describe a senescent erythrocyte
Decreased membrane continuity
Decreased enzyme activity
Increased [methaemoglobin] (oxidized Hb)
100
Describe clot retraction in haemostasis and the result.
Serum oozes out of fibrin lattice (erythrocytes, leukocytes trapped), bringing the tissue edges together for repair
101
In which pathways of Haematopoiesis is G-CSF involved?
Myeloid Stem Cell growth into Granulocytes
102
Which factor breaks down stable fibrin into soluble fragments?
Plasmin
103
How are thrombocytes formed, and what factor is involved?
Fragments that peel off megakaryocytes in marrow; stimulated by liver release of thrombopoietin, which increases megakaryocyte synthesis
104
Transport pathway for wastes in body fluids
ICF -> ISF -> lymph/blood capillaries
105
How do folic acid & Vitamin B12 affect erythropoiesis?
Act as cofactors for erythropoietic enzymes
106
What type of stem cells do pluripotent stem cells become if they are going to become granulocytes?
Myeloid
107
Major cation(s) in ECF: ISF
Na+
108
Describe the (Reduction &) Incorporation step of iron metabolism
Reduce Fe3+ to Fe2+, incorporate it into haem in mitochondria, and then incorporate haem into haemoglobin in the cytoplasm
109
Describe the mechanism of vasoconstriction in haemostasis
Initial neurogenic spasm (~60s), then myogenic spasm (~20-30min)
110
Which types of plasma proteins are involved with the plasma Immune system?
Immunoglobins, complements
111
What initially activates XII in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?
Contact with negative charges on the activated platelets
112
Which 6 compounds/classes act as in vivo anticoagulants?
1. Antithrombin III (AT III)
2. Heparin & Heparan sulphate
3. Tissue factor pathway Inhibitor (TFPI)
4. Thrombomodulin
5. alpha-protease inhibitor
6. Protein C and co-factor, Protein S
113
Units of solute concentration & their relation
- mmol/L
- meq/L (mmol/L x z; z=valence)
- mosmol/kg H2O (# of osmotically active solutes x mmol/kg H2O)
- mosmol/L H2O (# of osmotically active solutes x mmol/L H2O)
114
Characteristics of Late erythroblast
Nucleus & cytoplasm shrinking
| Rapid Hb synthesis until almost all is present
115
Which 5 factors are key in haematopoiesis, in the Myeloid Stem Cell path?
1. Erythropoietin (EPO)
2. Granulocyte Colony Stimulating Factor (G-CSF)
3. Macrophage Colony Stimulating Factor (M-CSF)
4. Granulocyte/Macrophage Colony Stimulating Factor (GM-CSF)
5. Interleukin-3 (IL-3)
116
Major cation in ICF
K+
117
How does heparin prevent unnecessary coagulation in vitro?
Stimulates AT III (antithrombinase III) action
118
Result of dehydration, in terms of haematocrit
Increases to 70% BECAUSE OF DECREASE IN PLASMA VOLUME (same absolute volume of haematocrit)
119
Role of hemoglobin
Carry O2, CO2; act as main buffer in blood
120
Describe sickle cell anemia
Synthesize Haemoglobin S instead of alpha, ß globulins => decrease O2 carrying ability (anemia)
121
Difference between solute concentration in plasma and plasma water
In "plasma water" doesn't include the volume of the solutes in plasma (which is ~7% by volume), so [ ] in plasma water is greater than [ ] in plasma
122
What are the components of the complex that activates X in the Extrinsic Pathway of blood coagulation & clot formation in haemostasis? Does it have a name?
TF, VIIa, Ca++
| No name
123
Components of ECF & %
ISF (75%)
Plasma (20%)
Transcellular Fluid (5%)
124
What is t-PA?
(endothelial) Tissue-type Plasminogen Activator
125
Describe the effect of a Vitamin K deficiency
Inadequate production of several clotting factors: prothrombin, VII, IX, X
126
Role of Cl- and HCO3- in ECF
Attendant ions to Na+ - maintain electrical neutrality
127
What activates XII in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis (once process starts)?
Kallikrein; proteolytic
| +ve feedback on kallikrein production by XIIa
128
How does Tissue Factor Pathway Inhibitor (TFPI) prevent unnecessary coagulation?
Targets TF.VIIa.Ca++ complex (intrinsic pathway)
129
Function of Hormones in plasma
Physiological regulation
130
How is haemoglobin synthesized?
From haem (x4), globin chains (alpha x2, ßx2); in cytoplasm
131
Which factor stimulates AT III activity to prevent unnecessary coagulation in vitro?
Heparin
132
Describe the Common Pathway
- Thrombin (circulating) activates V->Va
- Va, Xa (Intrinsic/Extrinsic path), Ca++ form complex = Prothrombinase
- Prothrombinase activates prothrombin -> thrombin
- Thrombin feeds back (+) to first step (incr. Va, incr prothrombinase, incr thrombin)
- Thrombin hydrolytically cleaves fibrinogen -> fibrin monomers and fibrinopeptides
- Spontaneous polymerization to fibrin polymers
- Thrombin activates XIII -> XIIIa
- XIIIa catalyzes formation of fibrin lattice
133
Characteristics of Early erythroblast
Large
Nucleated
Rapid Hb synthesis
134
Which factors/proteins are involved with fibrinolysis?
t-PA, u-PA; inhibited by PAI-1, PAI-2; plasminogen, plasmin
135
Major anion(s) in ICF
phosphates, proteins
136
How does endothelial PGI2 prevent unnecessary coagulation?
(PGI2 = prostacyclin)
Increases blood flow to prevent platelet activation
Prevents platelet adhesion & aggregation
Vasodilator
137
Name the 6 main functions of plasma proteins
"ITH OVA!"
(plasma) Immune system
Transport
Hormones
Osmotic pressure maintenance
(blood) Viscosity maintenance
Acid-base equilibrium
138
What does a Late Erythroblast become, in the process of erythropoiesis?
Reticulocyte
139
How do sex steroids affect erythropoiesis?
Testosterone: promotes
Estrogen: inhibits
140
Characteristics of fibrin clot
Stable, cross-linked lattice
141
What is the goal of the Extrinsic and Intrinsic Pathways of blood coagulation & clot formation in haemostasis?
Conversion of X -> Xa for the common pathway
142
Which plasma proteins are involved with transport?
Albumin, lipoproteins, glycoproteins
143
Describe the uptake step of iron metabolism
Receptor-mediated endocytosis takes Fe3+ from transferrin into the bone marrow
144
What stimulates prokallikrein activation in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?
XIIa (+ve feedback, since prokallikrein -> kallikrein, kallikrein catalyzes XII -> XIIa)
145
Which factors are involved in forming Lymphocytes from pluripotent stem cells?
None (of the ones we studied)
146
Haemostasis is an integrated system. What does vessel damage instigate?
Vasoconstriction, Platelet Adhesion/Activation/Aggregation, Coagulation Cascade
147
What type of stem cells do pluripotent stem cells become if they are going to become erythrocytes?
Myeloid
148
Which 2 compounds act as in vitro anticoagulants?
1. Heparin
| 2. Ca++ Chelators: EDTA, Oxalate, Citrate
149
What is the goal of the Common Pathway?
Formation of a stable fibrin clot
150
Total ECF volume in typical adult human
14L
151
Describe von Willebrand disease
VIII/vWf deficiency -> poor platelet adhesion -> internal bleeding
152
Cause of haemolysis
Placing cell in hypotonic solution -> water moves into cell
153
What disease results from a platelet deficiency?
Thrombocytopaenia -> don't clot properly
154
Protein content level of ECF: ISF
low
155
What results from a deficiency of VIII?
Type A haemophilia (coagulation defect)
156
What happens in the platelet membrane during the aggregation step of platelet plug formation in haemostasis?
Negatively-charged phospholipids translocate to the outside of the membrane
157
What role does Ca++ play in the Extrinsic Pathway of blood coagulation & clot formation in haemostasis?
Combines with TF.VIIa to form the TF.VIIa.Ca++ complex
| Activates X -> Xa
158
What is u-PA?
(plasma) Urokinase-type Plasminogen Activator
159
Which steps of erythropoiesis involve cytokines?
Formation of BFU-E, CFU-E, Proerythroblasts
160
Describe the Transport step of iron metabolism
Transferrin binds 2 Fe3+
161
What is an excess of platelets called?
Thrombocytosis
162
Haemostasis is an integrated system. What does Vasoconstriction instigate?
Platelet Adhesion/Activation/Aggregation
163
Main source of EPO in adults
Kidneys (peritubular interstitial cells)
164
What activates V in the Common Pathway of blood coagulation & clot formation in haemostasis?
Thrombin (circulating)
165
What are the three classes of anticoagulants in intact blood vessels?
1. Physical factors
2. Vasodilators
3. Anticoagulants
166
Which factors are involved in forming Thrombocytes from pluripotent stem cells?
EPO, GM-CSF, IL-3
167
Which factor acts as a vasodilator & prevents platelet adhesion/aggregation to prevent unnecessary coagulation?
Endothelial NO
168
Which body fluid compartment(s) has/have K+ as the major cation?
ICF
169
How do Ca++ chelators prevent unnecessary coagulation?
Remove Ca++ (can't form protease complexes: TF.VIIa.Ca++, VIIIa.IXa.Ca++, Va.Xa.Ca++ from Extr, Intr, Comm pathways resp)
170
How are anions and cations related in body fluid?
[cations]=[anions] in meq/L (using valence)
171
Normal thrombocyte concentration
250 000/mm^3
172
In which pathways of Haematopoiesis is M-CSF involved?
Myeloid stem cell growth in monocytes
173
What activates prothrombin in the Common Pathway of blood coagulation & clot formation in haemostasis?
Prothrombinase
174
What role does XIa.HMWK play in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?
Activates IX -> IXa
175
Major cation(s) in ECF: plasma
Na+
176
What results from a VIII/vWf deficiency?
von Willebrand disease (coagulation defect)
177
What do platelets contain? (granule types)
Dense granules, and alpha granules
178
Name the three types of coagulation defects
1. Vitamin K deficiency
2. Haemophilia
3. von Willebrand disease
179
What is the cofactor for conversion of XII -> XIIa in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?
High Molecular Weight Kininogen (HMWK)
180
How is plasma volume measured?
1. Inject known amt of dye/* of known conc. that will ONLY spread in plasma (e.g. attach to albumin)
2. Let equilibrate
3. Draw blood sample and measure dye/* conc.
4. Use Ci*Vi = Cf*Vf => Vf = Ci/Cf * Vi to get plasma volume
181
Which factors are involved in forming Monocytes from pluripotent stem cells?
M-CSF, GM-CSF, IL-3
182
Describe the oxidation step of iron metabolism
Caeruloplasmin (uses Cu) oxidizes Fe2+ -> Fe3+
183
Protein content of body fluid compartments, from highest to lowest
ICF > ECF: plasma > ECF: ISF
184
How does AT III prevent unnecessary coagulation?
(AT III: Antithrombin III)
| Targets thrombin, IXa, Xa
185
Function of lipoproteins in plasma
Transport lipids
186
What does a Reticulocyte become, in the process of erythropoiesis?
Erythrocyte
187
Total ISF volume in typical adult human
Interstitial fluid; 10.5L
188
What does a Burst Forming Unit Erythroid (BFU-E) become, in the process of erythropoiesis?
Colony Forming Unit Erythroid (CFU-E)
189
Which factors target complexes to prevent unnecessary coagulation?
TFPI (TF.VIIa.Ca++)
Protein C w/cofactor Protein S (Va -> Va.Xa.Ca++; VIIIa -> VIIIa.IXa.Ca++)
alpha-Protease Inhibitor (IXa -> VIIIa.IXa.Ca++)
AT III (IXa -> VIIIa.IXa.Ca++; Xa -> Va.Xa.Ca++)
190
What is tenase, and which pathway is it used in?
VIIIa.IXa.Ca++, intrinsic
191
Which body fluid compartment(s) has/have Na+ as the major cation?
ECF: plasma & ISF
192
Which anticoagulation factor(s) activate(s) AT III?
(AT III: Antithrombin III)
| Heparin (in vivo & in vitro), heparan sulphate (in vivo only)
193
Main source of EPO (fetus)
liver
194
Result of polycythemia, in terms of haematocrit
Increase to ~70% (instead of normal 40-45%)
195
What role does Ca++ play in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?
Combines with VIIIa, IXa to form tenase
| Activates X->Xa
196
In which pathways of Haematopoiesis is GM-CSF involved?
Myeloid stem cell growth into all derivatives: erythrocytes, thrombocytes, granulocytes, monocytes
197
Which body fluid compartment(s) has/have proteins & phosphate as the major anions?
ICF
198
Cause of crenation
Placing cell in hypertonic solution -> water moves out
199
What are the components of prothrombinase?
Va, Xa, Ca++
200
Describe Thalassemias and their cause
inherited; reduced/absent synthesis of one or more globin chains => no haemoglobin
201
How are plasma proteins involved with maintaining acid-base equilibrium?
Uptake/conversion of CO2/HCO3-/H2CO3 in respiration
202
Haemostasis is an integrated system. What does Platelet Adhesion/Activation/Aggregation instigate?
Coagulation Cascade (mutual positive feedback)
Platelet Plug Formation
Clot Formation
203
Roles of blood & body fluids in protection (2)
```
Haemostasis (platelet aggregation, blood coagulation)
Immune Reactions (plasma & blood cells)
```
204
What does a pluripotent stem cell become, in the process of erythropoiesis?
Burst Forming Unit Erythroid (BFU-E)
205
What activates XI in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?
XIIa.HMWK
206
Which factors are involved in forming granulocytes from pluripotent stem cells?
G-CSF, GM-CSF, IL-3
207
What are the two types of Haemophilia?
Type A: VIII deficiency
Type B: IX deficiency
(missing coagulation factors)
208
What do platelets store in dense granules?
Ca++, ADP, ATP, serotonin
209
What does a Colony Forming Unit Erythroid (CFU-E) become, in the process of erythropoiesis?
Proerythroblast
210
Which factors are involved with the extrinsic pathway?
Tissue factor, VII->VIIa, X->Xa
211
Which factor is common to the Extrinsic and Intrinsic Pathways?
X (Xa)
212
Function of complements in plasma
Immune response
213
What are the causes of hyperfibrinolysis?
Genetic or acquired
214
What activates X in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?
VIIIa.IXa.Ca++ (Tenase)
215
Normal erythrocyte concentration
5million/mm^3
216
What causes von Willebrand disease?
Inherited VIII/vWf deficiency
217
Function of transferrin in plasma
Bind & transport Fe3+
218
Which factors target thrombin to prevent unnecessary coagulation?
Antithrombin III, Thrombomodulin
219
Which factor uses physical means to prevent unnecessary coagulation?
Intact smooth endothelial lining (-ve glycocalyx on lining and on platelets repel, preventing adhesion)
220
Negatively-charged phospholipids translocate to the outer platelet membrane during aggregation. What effect does this have during blood coagulation & clot formation in haemostasis?
**Initiates coagulation cascade**
Platelet autolysis forms fibrin
Clot forms
... eventually, fibrinolysis
221
Describe the cause of a Vitamin K deficiency
Antibiotic inhibits bacterial production of Vitamin K
222
Normal plasma %
55-60%
223
Describe the absorption step of iron metabolism
Fe2+ absorbed from gut, into plasma
224
What activates IX in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?
XIa.HMWK
225
What is the source of Xa in prothrombinase?
Intrinsic/Extrinsic Pathway
226
Stages/formations of erythropoiesis
```
Pluripotent Stem Cell
Burst Forming Unit Erythroid (BFU-E)
Colony Forming Unit Erythroid (CFU-E)
Proerythroblast
Early Erythroblast
Late Erythroblast
Reticulocyte
Erythrocyte (mature)
```
227
What is PAI-1 and what does it do?
endothelial tissue Plasminogen Activator Inhibitor; prevents plasminogen -> plasmin
228
What is a platelet deficiency called?
Thrombocytopaenia
229
In which pathways of Haematopoiesis is IL-3 involved?
Myeloid stem cell growth into all derivatives: erythrocytes, thrombocytes, granulocytes, monocytes
230
Describe hyperfibrinolysis
PAI-1 deficiency -> dissolve clots immediately -> no haemostasis (like haemophilia)
231
Haemostasis is an integrated system. What does Clot formation instigate?
Haemostasis
232
Name the three diseases related to haemoglobin
1. Porphyrias
2. Thalassemias
3. Sickle Cell (Anemia)
233
Describe the characteristics of the extrinsic pathway
Activated immediately
Uses non-circulating components
Goal: Convert X -> Xa for the Common Pathway
234
How are the zymogens of most proteins involved with haemostasis activated, and what do most of the proteins do?
Proteolytic cleavage; act as proteases for the next zymogen
235
Which factor targets thrombin (only) to prevent unnecessary coagulation?
Thrombomodulin
236
Which factors target IXa to prevent unnecessary coagulation?
AT III, alpha-protease inhibitor
237
What are the functions of the factors that platelets store in alpha granules?
Adhesion factor, coagulation factor, platelet-derived growth factor
238
Describe the causes of vascular defects
Congenital or acquired
239
What activates XIII in the Common Pathway of blood coagulation & clot formation in haemostasis?
Thrombin
240
What role does thrombin play in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?
Activates VIII (released from vWf) -> VIIIa
241
What disease results from an excess of platelets?
Thrombocytosis (platelet abnormality) -> clot too easily
242
Describe the two types of platelet abnormalities & their phenotypes
thrombocytopaenia - deficiency, no clotting
| thrombocytosis - excess, too much clotting
243
Normal % haematocrit
40-45%
244
Haemostasis is an integrated system. What does the coagulation cascade instigate?
Platelet Adhesion/Activation/Aggregation (mutual positive feedback)
Clot formation
245
Function of Immunoglobins in plasma
Immune response
246
What stabilizes the fibrin cross-links in the Common Pathway of blood coagulation & clot formation in haemostasis?
XIIIa
247
What is the goal of blood coagulation & clot formation in haemostasis?
Digest fibrinogen with thrombin, to form (stable, insoluble) fibrin
248
How do intact blood vessels physically prevent unnecessary coagulation?
Negatively charged glycocalyx on both smooth endothelial lining and platelets -> prevents adhesion
249
Purpose of haemostasis
Seal injured blood vessel, maintain blood fluidity, and dissolve clot after coagulation
250
Function of haptoglobins in plasma
Bind free Haemoglobin to prevent excretion
251
Which factor targets thrombin, IXa, Xa to prevent unnecessary coagulation?
Antithrombin III (AT III)
252
What process are t-PA and u-PA involved in, and what is their role?
Fibrinolysis
| Activate plasminogen -> plasmin
253
What role does Va play in the Common Pathway of blood coagulation & clot formation in haemostasis?
Complexes with Xa, Ca++ to form Prothrombinase
| Activates Prothrombin -> Thrombin
254
Haemostasis is an integrated system. What causes Vasoconstriction?
Vessel damage
255
What role does VIIIa play in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?
Combines with IXa, Ca++ to form tenase
| Activates X->Xa
256
How does Thrombomodulin prevent unnecessary coagulation?
Targets thrombin
257
Describe the process of the Extrinsic Pathway of blood coagulation & clot formation in haemostasis.
- Tissue Factor (expressed on vascular membrane) is exposed
- TF acts as VII receptor, NON-PROTEOLYTIC activator to VIIa
- TF.VIIa binds Ca++ from activated platelets
- TF.VIIa.Ca++ complex: proteolytic X -> Xa
258
Haemostasis is an integrated system. What causes Platelet Plug formation?
Platelet Adhesion/Activation/Aggregation
259
What disease results from a PAI-1 deficiency?
Hyperfibrinolysis (dissolve clots too easily)
260
Name the 6 steps in Iron Metabolism
1. Absorption
2. Oxidation
3. Transport
4. Uptake
5. (Reduction &) Incorporation
6. Storage
261
Name the four types of haemostatic disorders
1. Vascular defect
2. Platelet abnormalities
3. Hyperfibrinolysis
4. Coagulation defects
262
Result of anemia, in terms of haematocrit
Decreases to 15-30% (instead of 40-45%)
263
Which factor is usually carried by von Willebrand factor?
VIII
264
What role does thrombin play in the Common Pathway of blood coagulation & clot formation in haemostasis?
Activates V -> Va (+ve feedback)
Activates XIII -> XIIIa
Hydrolyzes fibrinogen -> fibrinopeptides + fibrin monomers
265
Which factor stimulates AT III action to prevent unnecessary coagulation in vivo?
Heparin and heparan sulphate
266
Function of Caeruloplasmin in plasma
Bind Cu to catalyze Fe2+ oxidation to Fe3+
267
Which structures prevent blood loss from an intact vessel?
Endothelium and Sub-endothelium (basement membrane)
268
Haemostasis is an integrated system. What causes Platelet Adhesion/Activation/Aggregation?
```
Vessel damage
Coagulation Cascade (mutual feedback)
Vasoconstriction
```
269
Describe Porphyrias & its cause
Accumulation of porphyrins & precursors in liver and bone marrow => haem synthesis disorder
270
Which factors target VIIa to prevent unnecessary coagulation?
TFPI (targets TF.VIIa.Ca++ complex)
271
Which body fluid compartment(s) has/have Cl- as the major anion?
ECF: plasma & ISF
272
What activates VII in the Extrinsic Pathway of blood coagulation & clot formation in haemostasis? Proteolytic?
Tissue Factor (on vascular membrane); non-proteolytic
273
What activates VIII in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?
Thrombin (from the common pathway)
274
List the four main steps of haemostasis
1. Vasoconstriction
2. Formation of a platelet plug
3. Blood coagulation & stable clot formation
4. Clot retraction & fibrinolysis
275
What role does Xa play in the Common Pathway of blood coagulation & clot formation in haemostasis?
Complexes with Va, Ca++ to form prothrombinase
| Activates prothrombin -> thrombin
276
What does a Proerythroblast become, in the process of erythropoiesis?
Early erythroblast
277
What are the inhibitors of t-PA and u-PA called?
PAI-1, PAI-2 (Plasminogen Activator Inhibitor; 1 is from endothelial tissue, 2 is from placenta)
278
How does VIII enter the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?
Release from vWf, which carries it in blood
279
Haemostasis is an integrated system. What causes the coagulation cascade?
Vessel damage
| Platelet Adhesion/Activation/Aggregation (mutual feedback)
280
What role does IXa play in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?
Combines with VIIIa, Ca++ to form tenase
| Activates X->Xa
281
What activates X in the Extrinsic Pathway of blood coagulation & clot formation in haemostasis?
TF.VIIa.Ca++ complex (TF: tissue factor)
282
Which factors are involved in forming erythrocytes from pluripotent stem cells?
EPO, GM-CSF, IL-3
283
What does a Early erythroblast become, in the process of erythropoiesis?
Late Erythroblast
284
What role does Ca++ play in the Common Pathway of blood coagulation & clot formation in haemostasis?
Complexes with Va, Xa to form prothrombinase
| Activates prothrombin -> thrombin
