Lecture - Mixed Flashcards
1
Q
The maintenance of circulatory hemostasis is achieved through the process of balancing
A
bleeding (hemorrhage)
clotting (thrombosis)
2
Q
4 Major Components of Hemostasis
A
Vascular system
Thrombocytes (platelets)
Blood Coagulation Factors
Ultimate tissue repair
3
Q
Processes involved in hemostasis following injury to a small blood vessel:
A
- Blood vessel spasm
- Formation of a platelet plug
- Contact among damaged blood vessel, blood platelet, and
coagulation proteins - Development of a blood clot around the injury
- Fibrinolytic removal of excess hemostatic material to
reestablish vascular integrity
4
Q
Types of Blood Vessels
A
Arteries - arterioles
Veins - venules
Capillaries
5
Q
Tissue Zones
A
- Tunica adventitia / Tunica
Externa - Tunica media
- Tunica intima / Tunica interna
6
Q
a reflex in which blood vessels narrow to increase blood pressure.
A
Vasoconstriction
7
Q
Vasoconstriction caused by
A
thromboxane A2
8
Q
promotes vasoconstriction
A
Epinephrine
serotonin
9
Q
ensures rapid lysis of fibrin clots
A
plasminogen
10
Q
Regulates the permeability of the inner vessel wall and provides the principal stimulus to thrombosis following injury to a blood vessel.
A
Endothelium
11
Q
Involved in the clotting process by producing or storing clotting components
A
Endothelium
12
Q
Rich with plasminogen activator, which, if appropriately stimulated, is released and activates plasminogen
A
Endothelium
13
Q
synthesized by the endothelium from prostaglandin precursors and strongly inhibits platelet aggregation and adhesion
A
prostacyclin
14
Q
where they act as modulators of vasomotor tone, cell proliferation, and hormone production
A
Endothelins
15
Q
Endothelin-1 is produced in
A
endothelial cells
vascular smooth muscle cells
16
Q
endothelin acts as modulator in
A
vasomotor tone
cell proliferation
hormone production
17
Q
Endothelin-2 produced in
A
predominantly within the kidney and intestine
smaller amounts produced in the myocardium, placenta, and uterus
18
Q
Endothelin-3 found in
A
high concentrations in the brain - proliferation and development in neurons and astrocytes
found throughout the gastrointestinal tract and in the lung and kidney.
19
Q
play an important role in the initiation, progression, and clinical complications of various forms of inflammatory and degenerative vascular diseases.
A
Endothelial Dysfunction
20
Q
Stimuli of Endothelial Dysfunction
A
Immunoregulatory Substances (TNF & IL-1)
Viral Infection and Transformation
Bacterial Toxins
Cholesterol / Oxidatively modified lipoproteins
21
Q
Disruption of the endothelium directly activates all four components of hemostasis.
• After this event, the following events take place:
A
- Initially, rapid vasoconstriction for up to 30 minutes reduces blood flow and promotes contact activation of platelets and coagulation factors.
- In the second phase, platelets adhere immediately to the exposed subendothelial connective tissue, particularly collagen. The aggregated platelets enhance sustained vasoconstriction by releasing thromboxane A2 and vasoactive amines, including serotonin and epinephrine.
- In the third phase, coagulation is initiated through both the intrinsic and extrinsic systems.
- Finally, fibrinolysis occurs following the release of tissue
plasminogen activators (t-PAs) from the vascular wall. Fibrinolytic removal of excess hemostatic material is necessary to reestablish vascular integrity.
22
Q
Essential Factors for Vascular Integrity
A
- Circulating functional platelets
- Adrenocorticosteroids
- Ascorbic Acid
23
Q
The integrity of arterioles and venules depends on
A
vasoconstriction
platelet plug
fibrin clot
24
Q
ultimate importance in damaged arteries
A
Vasoconstriction
25
Veins contain what percent of blood volume
70%
26
Veins, which contain 70% of the blood volume, may rupture with
slight increase in hydrostatic pressure
27
proceeds initially through a phase characterized by mitotic division of a progenitor cell, followed by a wave of nuclear endoreduplication.
Megakaryocytopoiesis
28
proceeds initially through a phase
characterized by mitotic division of a progenitor cell,
followed by a wave of nuclear endoreduplication
Megakaryocytopoiesis
29
the process in which chromosomal material (DNA) and the other events of mitosis occur
Endoreduplication
30
stimulate the production and maturation of megakaryocytes
Thrombopoietin
31
Thrombopoietin activity results from several different cytokines
erythropoietin
IL-3
granulocyte-macrophage colony-stimulating factor (GM-CSF)
32
erythropoietin, IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been shown to be able to increase
megakaryocyte size
maturational stage
ploidy
33
10-24 mm, round nucleus, N/C ratio 3:1
MEGAKARYOBLAST
34
chromatin of megakaryoblast
homogenous
| loosely organized
35
granules are absent by wright's stain
megakaryoblast
36
Bone Marrow: 20% of megakaryocyte precursors in bone marrow
| Peripheral Blood: 0%
megakaryoblast
37
15-40 mm, indented nucleus, condensed chromatin
promegakaryocyte
38
granules are present, n/c ration 1:2
PROMEGAKARYOCYTE
39
REFERENCE INTERVAL:
Bone Marrow: 25% of megakaryocyte precursors in bone marrow
Peripheral Blood: 0%
PROMEGAKARYOCYTE
40
largest bone marrow cells, ranging up to 160 mm in size
MEGAKARYOCYTE
41
MEGAKARYOCYTE n/c ratio
1:12
42
multilobular, not multinucleated
megakaryocyte
43
2 to 4 mm
| no nucleus
platelets
44
Platelet's color of cytoplasm and granules
cytoplasm - light blue
| granules - fine red-purple
45
appearance of inactive or unstimulated platelet
thin
| smooth surfaced disc
46
alteration in cellular shape of platelet is triggered by
cytoplasmic calcium
47
Stronger stimulation causes platelets to
become sticky without losing their discoid shape
48
GLYCOCALYX also known as
fluffy coat
49
these surrounds the cellular membrane of the platelet externally.
glycocalyx or fluffy coat
50
unique among the cellular components of the blood
glycocalyx or fluffy coat
51
glycocalyx or fluffy coat is composed of
plasma proteins and carbohydrate molecules
52
* located directly beneath the cell membrane of platelet
* provide structure of the platelet to maintain its discoid shape
* maintains the position of the organelles
MICROFILAMENTS & MICROTUBULES
53
• secondary system of microfilaments is functional in
internal organization
| secretion of blood coagulation products, such as fibrinogen
54
most abundant granules
alpha
55
enumerate alpha granules
```
heparin-neutralizing platelet factor 4
beta-thromboglobulin
platelet-derived growth factor
platelet fibrinogen
fibronectin
vwf
thrombospondin
```
56
dense granules also known as
delta granules
57
- store hydrolase enzymes
lysosomes
58
Dense or Delta Granules contains
Serotonin
ADP
ATP
Calcium
59
Other Cytoplasmic Constituents
* Contractile proteins, including actomyosin (thrombosthenin), myosin, and filamin
* Glycogen
* Enzymes of the glycolytic and hexose pathways
60
megakaryocyte produces
1,000-2,000 platelets
61
Marrow transit time / maturation period of megakaryocyte
5 days
62
Platelets initially enter the spleen & remains for
2 days
63
_____ of the total number of platelets are in systemic circulation
2/3
64
____ exists as pool of platelets in the spleen that free exchange with the general circulation
1/3
65
A normal person has an average of ____ platelets in the systemic
circulation.
Range:
250 × 109/L
| 150 ×109/L to 450 × 109/L
66
Platelet turnover or effective thrombopoiesis averages
35 ×109/L ± 4.3 × 109/L/day
67
The life span of a mature platelet is
9.0 days ± 1 day
68
At the end of their life span, platelets are phagocytized by the
liver and spleen
| mononuclear phagocytic system
69
2 important players in primary hemostasis
blood vessels
| platelets
70
Largest artery
aorta
71
- if blood comes out from vessel, instead of closed system what will happen
formation of petechiae
purpura
ecchymoses
72
- noncontact surface in vivo
Endothelium
73
contact surface, when exposed hemostatic mechanism will start
Sub endothelium
74
involved in secondary hemostasis
Blood coagulation factors
75
Mechanism of hemostasis only works on
medium sized vessels
76
- end point of primary hemostasis
Formation of platelet plug
77
doesn’t have tunic
Capillaries
78
epithelium of Surface endothelium
simple squamous
79
found in tunica media
collagen/smooth muscles
80
vasobasorum
blood vessels that gives nourishment and blood to blood vessels
81
vasobasorum found in
tunica externa
82
- product of activated platelet that will prolong platelet adhesion and vasoconstriction, byproduct of eicosanoids or the thromboxane pathway of cyclooxygenase pathway
Thromboxane A2
83
- only interleukins secreted by monocyte and macrophage
Tumor necrosis factor/IL1
84
these makes collagen
fibroblasts
85
endo multiplication of DNA, only lobes increase called polyploid cells
Endomitosis
86
the normal percentage of megakaryocytic cells are found in the bone marrow
1%
87
The earliest recognizable by microscopy
megakaryoblast
88
biggest in bone barrow or mother cell of platelets
Meta mega/mature karyocyte
89
no cytokinesis or late telophase, formation of?
Polyploids
90
simple endothelial cells that lines delicate organs like liver, spleen, BM
Sinusoids
91
Sinusoids lines delicate organs like
BM
liver
spleen
92
Platelet will stay at sinusoids for
9-11 days or 8-10 days
93
has big role on erythropoiesis and has a big role on thrombopoiesis
IL-3
94
pan myeloid factor, affects all cell line
• GM-CSF
95
more ploidy
greater number of lobes
96
how to get chromosome numbers
2n
97
Megakaryocytes are not usually found in blood, what happens if there are some?
megakaryocytic leukemia
98
Do we find platelets in bone marrow?
yes
99
Most important criterion in determining the age of the cell
chromosome- fine and linear
100
Platelets take what dyes
azure dyes
101
zone for adhesion of platelets
peripheral zone
102
zone where actomyosin or thrombosthenin, microfilaments, microtubules are found
Sol-gel zone
103
responsible for disk shape
microtubules
104
Not greatly stainable under electron micrographs they are gray colored
Alpha granules
105
Platelets can do aerobic glycolysis due to presence of
mitochondria
106
- an internal membrane structure found in platelets
Canalicular system
107
Adhesion is direct or indirect
indirect
108
vWF produced in
Weibel-palate bodies
109
Weibel-palate bodies found in
plasma
110
these also produce vWF aside from Weibel-palate
Megakaryocytes
111
3 primary steps in hemostasis
Adhesion
secretion (release mechanism)
aggregation
112
Upon exposure of sub endothelium, this will happen
adhesion
113
a loose mass (mesh) that will be strengthened by secondary hemostasis
Platelet plug formation
114
glycoproteins attached on surface of platelets
GP1B
GP5
GP9
115
this will engender (cause) platelet aggregation
ADP
116
receptors for fibrin
IIb
| IIIa
117
Functional platelets adhere to
subendothelial collagen
118
these are assessed using platelet aggregometry
Platelet adhesion, aggregation, and secretion
119
PRP aggregometry is performed using
a light-transmittance aggregometer
120
whole-blood platelet aggregometry, platelet aggregation is measured by
electrical impedance.
121
used for the simultaneous measurement of platelet aggregation and the secretion of adenosine triphosphate (ATP) from activated platelet dense granules
Whole Blood/Optical LumiAggregometer
122
these are used to test for abnormalities of specific membrane binding sites.
platelet agonists
123
Aggregation is dependent in
calcium and energy (ATP)
124
Aspirin (blood thinner) will block
cyclooxygenase
thromboxane
eicosanoid
prostaglandin pathways
to stop production of thromboxane A2
125
potent platelet aggregator and stimulator
Thromboxane A2
126
blood clot, aggregates of platelets superimposed by fibrin
Thrombus
127
Secondary hemostasis endpoint
- stable fibrin clot in vivo (fibrin polymer)
128
Electronic particle counter principle
coulter principle
| works in electrical impedance
129
Template bleeding time
obsolete, used to be the gold standard
130
When antibody coats a particle, it will activate
classical pathway of complements that will result in lysis of platelets
131
Not enough glycoproteins 1B, 5 and 9
Bernard-Soulier syndrome
132
Not enough glycoproteins 2b, 3a
Glanzmann diseases
133
Defect usually is in
release mechanism
134
- reactive condition
thrombocytosis
135
release of Pf3 or PPL(phospholipid)- which plays a big role in forming stable fibrin clot.
secondary hemostasis
136
substance responsible for extrusion of serum from the clot - clot retraction
platelet contractile protein, THROMBOSTHENIN/ACTOMYOSIN
137
plays a big role in forming stable fibrin clot in secondary hemostasis
Pf3 and phospholipid
138
Functions of platelets
Primary hemostasis
Secondary hemostasis
Clot retraction
Localization of bacteria and other small objects
139
Platelets are composed of
60% proteins
30% lipids
8% carbohydrate
Mainly glycogen, sulfate mucopolysaccharides, various minerals, water and nucleotides
Lipids- phosphatidylethanolamine and phosphatidylserine
140
4 parts of platelet
Peripheral zone
Sol-gel zone
Organelle zone
Membranous system
141
the fuzzy coating, primarily composed of glycoproteins (GP)
Glycocalyx
142
receptors for vWF
GPlb/V/IX
143
major component of plasma membrane
arachidonic acid
144
lies directly beneath the glycocalyx and is composed of asymmetrically distributed phospholipids embedded with integral proteins
plasma membrane
145
site where messages from the external membrane are translated into chemical signals causing activation and a physical change in the platelets.
sub membranous area
146
receptors identified in sub membranous area
```
ADP
collagen
serotonin
epinephrine
thrombin
vWF
Factor V
Factor Xa
```
147
zone that lies beneath the plasma membrane.
Sol-gel zone
148
Sol-gel zone is composed of
Microfilaments and microtubules
149
responsible for clot retraction
actomyosin (thrombosthenin)
150
maintains the platelet's disc shape
microtubules - tubulin
151
called the centromere
Organelle zone
152
Part where the secretory products come from.
Organelle zone
153
play an important role in platelet aggregation especially its product, ADP
Dense/delta granules
154
The platelets can also do anaerobic glycolysis due to
glycogen granules
155
2 types of membranous system
dense tubular system
| surface connected system
156
derived from smooth endoplasmic reticulum and sequesters calcium for platelet activation processes.
dense tubular system-
157
an invagination of the plasma membrane, acts as a canal for the release of the granule contents and cytoplasm to the exterior of the platelet
surface connected system
158
This system is also involved in platelet phagocytosis.
surface connected system
159
This is found in hemorrhagic diathesis(( bleeding tendency)
Hemmeler’s anomaly
| Hermansky-pudlak syndrome
160
defect when no azurophilic granules is found in cytoplasm of
| platelets. The absolute platelet count is within reference range.
Hemmeler’s anomaly
161
Platelets have storage pool deficiency.
Hermansky-Pudlak syndrome
162
found in albinos , there is hemorrhagic diathesis, dense bodies storage pool disease
Hermansky-Pudlak syndrome-
163
appearance of atypical platelet
giant 4-7 um
increase size of hyalomere
granule is decreased or absent
bizarre or irregular shapes
164
- defects where there is decreased number of alpha granules
Gray platelet syndrome
165
when platelets are found encircling the borders of neutrophils, seen in patients whose blood was anticoagulated with EDTA
Platelet satellitosis/ platelet satellitism
166
This phenomenon is thought to be due to a serum factor that reacts in the presence of EDTA.
Platelet satellitosis/ platelet satellitism
167
occurs within the intravascular
| compartment lined with endothelium
HEMOSTASIS
168
A tightly regulated balance between formation and dissolution of hemostatic plugs modulated by a series of enzymes and scaffolding proteins.
PHYSIOLOGIC HEMOSTATIC SYSTEM
169
Factors involved in Normal
| Hemostasis and Thrombosis
Plateletes, Granulocytes & Monocytes
Coagulation Protein Sytem (Clot Forming)
Fibrinolysis Protein System (Clot Lysing)
Anticoagulation Protein System ( Regulating)
170
serves to form thrombin that initiates the proteolysis of fibrinogen, leading to fibrin clot formation
Coagulation System (Clot Forming)
171
→ functions to lyse the clot formed by thrombin
Fibrinolytic Sytem (Clot Lysing)
172
regulates all enzymes of the coagulation and fibrinolytic systems, so that no inappropriate excess of clotting or bleeding occurs.
Anticoagulation System (Regulating)
173
Vasoconstriction is a short-lived reflex reaction of the smooth muscle in the vessel wall produced by the
sympathetic branches of the autonomic nervous system
174
increases the adhesiveness of platelets
ADP
175
Platelet during adhesion will transform from ________ to ______ which produces surface membrane organization
disc shape to a sphere with pseudopods
176
Internal contraction of the platelet results in release of granular contents of
alpha granules
dense granules
lysosomal granules
177
Platelets adhere at sites of mechanical vascular injury and then undergo activation and express what functional glycoprotein ---- also referred to as?
IIb/IIIa
| Alpha 2b Beta 3
178
Which receptors will mediate the recruitment of local platelets by forming fibrinogen bridges between platelets—a process called platelet cohesion.
glycoprotein IIb/IIIa
179
A process forming fibrinogen bridges between platelets
platelet cohesion
180
Glycoprotein ____ is specific for
| platelets.
IIb/IIIa
181
Glycoprotein ______ is the most abundant platelet membrane protein (with approximately _______ receptors per platelet).
IIb/IIIa
| 50,000
182
gold standard test to determine platelet function.
Platelet aggregation
183
Agents capable of producing platelet aggregation in vitro (an energy dependent process):
Collagen
Proteolytic enzymes (thrombin)
Biological amines (epinephrine and serotonin)
184
results from bridges formed by fibrinogen in the presence of calcium which produces sticky surface on platelets
Aggregation
185
If these aggregates are reinforced by fibrin, they are referred to as a
thrombus
186
Aggregation of platelets by at least one pathway can be blocked by substances such as:
PGE (prostaglandin E)
| adenosine
187
- provides basis for platelet consolidation & stabilization.
Fibrinogen
188
This process involves the precipitation of polymerized fibrin around each platelet
PLATELET PLUG CONSOLIDATION & STABILIZATION
189
Result of platelet plug consolidation and stabilization
fibrin clot
190
Fibrin clot will produce
irreversible platelet plug
191
Quantitative Determination of Platelet
Electronic particle counter
| examination of stained blood film
192
done if the platelet count is normal → assessment of platelet function
Qualitative Assessment of Platelet
193
Qualitative Assessment of Platelet
a. PBS
b. Platelet Count
c. Template Bleeding Time
d. Petechiometer
e. Platelet Aggregation
f. Platelet lumiaggregation (release)
g. Platelet Antibodies (IgM and IgG)
h. Platelet Membrane Glycoproteins
i. Platelet factor IV
k. Thromboxanes
194
In vivo measurement of platelet adhesion and aggregation on locally injured vascular subendothelium.
Bleeding Time with and without Aspirin
195
Provides an estimate of the integrity of the platelet plug and thereby measures the interaction between the capillaries and platelets
Bleeding Time with and without Aspirin
196
Reflects the number and quality of platelets, fibrinogen concentration, fibrinolytic activity, and packed red cell volume.
Clot Retraction
197
The degree of clot retraction is __________ to the number of
| platelets & __________ to the hematocrit and the level of the blood coagulation factor fibrinogen.
directly proportional
| inversely proportional
198
The principle of the test is that platelet-rich plasma is treated with a known aggregating agent. If aggregated, cloudiness or turbidity can be measured using a spectrophotometer.
Platelet Aggregation
199
Aggregating agents
```
ADP
Collagen
Epinephrine
Ristocetin
Snake venom
Thrombin
```
200
Available techniques can include complement fixation methods, lysis of chromium 51 labeled platelets, assays of platelet-bound immunoglobulins, and competitive inhibition assays.
Antiplatelet Antibody Assays
201
VASCULAR DISORDERS
1. Purpura associated with direct endothelial cell damage.
2. Purpura associated with an inherited disease of the connective tissue.
3. Purpura associated with decreased mechanical strength of the microcirculation.
4. Purpura associated with mechanical disruption of small venules.
5. Purpura associated with microthrombi (small clots).
6. Purpura associated with vascular malignancy.
202
Demonstrates the smallest platelets seen
Wiskott-Aldrich
| syndrome
203
Characterized by the presence of large platelets and the presence of Döhle-like bodies in the granulocytic leukocytes
May-Hegglin
| anomaly
204
Disorder that exhibits giant platelets and thrombocytopenia
Alport syndrome
205
Demonstrates the largest platelets. In this disorder, it has been demonstrated that the giant platelets are probably an artifact of the slide
Bernard-Soulier syndrome (giant platelet syndrome)
206
3 types of thrombocytopenia
Disorder of production
disorder of destruction or utilization
disorder of platelet distribution
207
Hereditary or familial thrombocytosis associated with ger_x0002_mline mutations of the thrombopoietin (THPO) gene in the THPO receptor (MPL) gene
THROMBOCYTOSIS
208
associated with myeloproliferative neoplasms and/or myelodysplastic disorders (clonal thrombocytosis associated with somatic mutations of JAK2[V617F], MPL, and additional currently unknown genes)
THROMBOCYTOSIS
209
reactive disease
secondary thrombocytosis
210
TYPES OF PLATELET DYSFUNCTION
a) Acquired
b) Drug-Induced
c) Platelet Membrane Receptors
d) Hereditary
211
Types of acquired platelet dysfunction
```
Myeloproliferative
Uremia
Miscellaneous
Paraprotein
Cardiopulmonary bypass and platelet function
```
212
Types of hereditary platelet dysfunction
i. Bernard-Soulier Syndrome
ii. Glanzmann Thrombasthenia and Essential Athrombia
iii. Hereditary Storage Pool Defect
