Test 3 week 6 Flashcards
(273 cards)
1
Q
The blood is composed of __ and ___
A
Cells and plasma
2
Q
What is plasma?
A
Blood without cells
3
Q
Cells make up ___ of our blood. Most of the cells are ___. Less than 1% are ___, and ____
A
Cells make up about 45% of our blood. Most of the cells are RBCs. Less than 1% are WBCs, and platelets
4
Q
All blood cells have limited life spans, meaning that our bodies ____
A
need to continuously produce our blood cells, whether they are RBCs or WBCs
5
Q
What are the 3 main blood cell types, where are they generated from and where are they found
A
RBCs, WBCs, and platelets.
Generated from a common stem cell in the bone marrow and are found in the blood
6
Q
What are WBCs mainly responsible for?
A
Mainly responsible for immunity responses and attacking different types of infections. They induce immune response
7
Q
What are the 3 main types of WBCs?
A
- Granulocytes(can see granules under the microscope?
- Monocytes
- Lymphomatics
8
Q
What are the types of granulocytes?
A
- Neutrophil (poly morphonuclear leucocytes-bcos they appear to be multi nuclei)
- Basophil
- Eosinophil
9
Q
Types of lymphocytes
A
- B lymphocytes
- T lymphcytes
10
Q
What is the main function of RBCs?
A
To transport O2 and CO2 using hemoglobin
11
Q
What is the main function of neutrophil?
A
Phagocytose and destroy invading bacteria
12
Q
What is the main function of eosinophil?
A
Destroy larger parasites and modulate allergic inflammatory responses
13
Q
What is the main function of basophils?
A
Release histamine (and serotonin in some species) in certain immune reactions
14
Q
What is the main function of monocytes?
A
Become tissue macrophages, which phagocytose and digest invading microorganisms and foreign bodies as well as damaged senescent cells
15
Q
What is the main function of B lymphocytes?
A
Make antibodies
16
Q
What is the main function of T lymphocytes?
A
Kill virus-infecting cells and regulate activities of other leucocytes
17
Q
What is the main function of natural killer (NK) cells?
A
kill virus- infected cells and some tumor cells
18
Q
What is the main function of platelets?
A
Initiate blood clotting
19
Q
Unlike ___, ___ stays within the vascular system
A
Unlike WBCs, RBCs stays within the vascular system
20
Q
Why would WBCs not be in the vascular system?
A
If there’s inflammation or some kind of infection in the body, WBCs squeeze out through the capillaries into the interstitial space to attempt to attack any kind of foreign particles or microbes
21
Q
___ lack a nucleus, ER, mitochondria, and ribosomes. Causing them to not be able to grow or divide
A
RBCs
22
Q
What is the main source of ATP generation of RBCs?
A
Anaerobic glycosis
23
Q
What are the 2 cells in the body that rely heavily on glucose and have alot of trouble oxidizing anything else?
A
RBCs and brain cells
24
Q
A developing RBC is called a ____. Once the RBC leaves it, its called a ____, and in it are the mitochondria and everything else that the RBC leaves behind
A
- Erythroblast
- Reticulocyte
25
Once RBCs are worn out what happens to them?
They are phagocytosed and digested by macrophages in the liver and spleen
26
What happens to hemoglobin transport if its not kept inside the RBC?
Hemoglobin can leak through capillary membranes into interstitial spaces or glomerular filtrate. The concentration will decrease if there's a continuous leak. (RBC prevents this)
27
____ contain large quantities of the enzyme carbonic anhydrase, which aids in the transport of CO2
Erythrocytes/ RBCs
28
What are the 3 forms that CO2 is transported?
- About 7% is dissolved in plasma
- 23% diffuses into the blood, combines with hemoglobin and is transported to the left.
- CO2 combines w/water and because the RBC has
the enzyme (carbonic anhydrase), this reaction can be very efficient and very fast in the RBC. CO2 is formed with H2O to form carbonic acid which is then going to
dissociate into bicarbonate and protons. bicarbonate is a very good buffer system
for CO2. bicarbonate (HCO3-) travels through the plasma once we reach the lungs
this reaction go into the reverse direction. which bicarbonate will then give us co2 and co2 is going to diffuse out into the alveoli and through expiration (out into the outside air) so overall, RBCs are imp for c02 transport as well because of the presence of carbonic anhydrase and hemoglobin we can transport 93% of CO2. the remaining 7% is dissolved in the plasma.
29
Why is the biconcave disk shape of an RBC important?
It is optimal for the RBC to be able to squeeze through tight and narrow passages in the circulation
30
Old RBCs become too fragile and are frequently ruptured as they squeeze through the red pulp of this organ. Removal of this organ will result in an abnormally high amount of old RBC circulating in the body
Spleen
31
There are more RBCs in a healthy ___, than in a healthy ___. And they can hold more hemoglobin
There are more RBCs in a healthy men, than in a healthy women
32
The ability of bone marrow to produce RBCs ___ with age
Reduce
33
RBCs are generated from ___, because they make up a tiny portion of the bone marrow population
Stem cells
34
Which cells are not developed in the bone marrow?
T- lymphocytes(thymus), macrophages and osteocytes (monocytes)
35
What is a colony stimulating factor (CSF)?
They are glycoproteins that may circulate in the blood and act as hormones or act directly in the bone marrow as local mediators, to help stem cells choose a path to develop.
36
What does erythropoietin (EPO) do as a CSF and where is it produced?
Its normally produced by the kidney, and it stimulates the production of RBCs. When there is a lot of it circulating, the myeloid progenitor are going to choose the path to erythocytes
37
If there is a high concentration of granulcytes (CSF), the myeloid progenitor are going to pick a path to produce ___
WBCs
38
Factors that increase O2 consumption(decreasing its levels in the body) will ___ the EPO levels in the kidney, hereby stimulating more RBCs production in the bone marrow. (same also happens when EPO levels are decreased in the bone marrow)
Factors that increase O2 consumption(decreasing its levels in the body) will increase the EPO levels in the kidney, hereby stimulating more RBCs production in the marrow
39
What happens when both of a person's kidneys have been removed?
The person becomes anemic due to EPO loss
40
Low O2 activates ____ which is a transcription factor. This then drives the cell to secrete ____, which acts on blood cells to stimulate ____ and formation of more capillaries and the growth of more vessels which spreads blood better
Low O2 activates *hypoxia inducing factor (HIF)* which is a transcription factor. This then drives the cell to secrete *vascular endothelial growth factor (VEGF)*, which acts on blood cells to stimulate *angiogenesis* and formation of more capillaries and the growth of more vessels which spreads blood better
41
Exercise ____ RBCs production, until it hits a plateau, where plasma volume ____. This is them compensated by a n ____ and the lasting effect is an ___ in total blood volume
Exercise *increase* RBCs production, until it hits a plateau, where plasma volume*decreases*. This is then compensated by an *increase in RBC volume* and the lasting effect is an *increase* in total blood volume
42
What are the 2 nutritional requirements that out bodies need to produce RBCs? These nutrients are essential for maturation of RBCs and DNA synthesis, and without the RBCs don't mature fast enough
Vitamin B12 and Folic acid
43
When RBCs don't proliferate as they are supposed to, they become larger than normal (macrocytic), which leads to a condition called _____. They also change shape
A condition called macrocytic anemia
44
What causes pernicious anemia?
Vitamin B12 deficiency
45
How does pernicious anemia occur?
- Parietal cells of the gastric glands secrete a glycoprotein called intrinsic factor (IF)
- IF is needed for the uptake of B12, and protecting it from digestion, until it binds to its receptors on the mucosal cells.
- Lack of IF decreases the availability of B12, even if it is plenty in out diet
- Lack of B12, causes macrocytic normochromic anemia( pernicious anemia is a type of this)
46
Pernicious anemia can also occur as a result of ___deficiency
folic acid
47
What does macrocytic normochromic anemia mean?
- Macrocytic: RBC is too large
- Normochromic: color is normal, because hemoglobin content is normal
* An RBC that has a normal color, but is too large*
48
What is bilirubin, where and how is it formed, and where is it secreted?
- Bilirubin is a yellow pigment
- It is secreted in the bile
- It is formed/metabolized in the liver
- It is formed by the break down of hemoglobin(after phagocytosis of an RBC), which breaks down into a heme group and a globin(the protein component). The heme group is then broken down into the iron which produces bilirubin.
49
What happens when the content of bilirubin increases greatly?
Jaundice
50
What causes an increase in bilirubin?
An increase in RBC degradation or obstruction in bilirubin secretion in the bille
51
What are the 2 types of jaundice caused by an increase of bilirubin?
- Hemolytic jaundice: when there is too much breakdown of RBCs and the body has trouble metabolizing the excess bilirubin. (seen in new borns, cos they have excess RBCs from their mothers)
- Obstructed jaundice: a condition where the liver is unable to excrete the bilirubin in the bile, which results in bilirubin being in the blood system, causing a build-up
52
How much iron is required daily for RBC generation? And where does it come from?
25 mg.
| 1-2 are used from diet, the rest is from recycling RBCs
53
What are ways to lose iron?
- Sweat
- Urine
- Bile
- Minor bleeding
54
67% of total body iron is bound to ____
heme in RBCs and muscle cells (myoglobin)
55
30% of iron is stored in ___ and ____
In macrophages and hepatic paranchymal cells
56
What king of anemia does iron deficiency lead to? And what does it mean?
Microcytic-Hypochromic Anemias
- Microcytic: cells are smaller in size
- Hypochromic: Hemoglobin content is decreased, so cells don't have their normal colors
57
What disorders are related to Microcytic-Hypochromic Anemias and why?
- Disorders of iron metabolism
- Disorders of globin synthesis.
- The heme group in hemoglobin needs iron, so a disorder in the metabolism of iron will lead to Microcytic-Hypochromic Anemia.
- Without globin, we can't form hemoglobin. (can also lead to tomicrocytic hypochromic anemia)
58
What is normocytic-normochromic anemia and what causes it?
Normal sized and normal hemoglobin content RBCs.
Caused by a deficiency in the total amount of RBCs present in the body
59
What are the factors that can cause a deficiency in the total amount of RBC in the body?
- Aplastic: loss of function of the bone marrow, leading to the body being unable to produce RBCs
- Post- hemorrhagic: acute/too much blood loss
- Acquired hemolytic: autoimmune destruction of the RBC
- Hereditary hemolytic: sickle cell
- Anemia of chronic inflammation: can be due to different factors
60
What are the types of myeloproliferative RBC disorders?
- Polycythemia
- Relative polycythemia
- Absolute polycythemia
- Polycythemia vera
61
What causes polycythemia?
Overproduction of red blood cells
62
What causes relative polycythemia?
- Dehydration
- Fluid loss which results in relative increases of RBC percentage, hence hemoglobin and hematocrit values (the actual number of RBC doesn't actually increase, its just more RBC relative to fluid, due to fluid loss)
63
What are the two types of absolute polycythemia and what causes them?
- Primary absolute: abnormality of stem cells in the bone marrow. And polycythemia vera (JAK2 mutation)
- Secondary absolute: increase in erythropoietin as a normal response to chronic hypoxia or an inappropriate response to erythropoietin-secreting tumors
64
What is polycythemia vera JAK2 mutation?
A stem cell disorder in which you have a hyperplastic bone marrow or alterations which will affect the JAK2 gene. This gene is then affected and mutated in a way the bone marrow keeps producing blood cells
65
What is polycythemia vera and what causes it?
An abnormal, uncontrolled proliferation of RBCs, WBCs, and platelets. Manifests as a result of increased RBC mass and hematocrit.
66
Polycythemia vera leads to...
- Increased blood viscosity(as a result of increased RBC mass)
- Hypercoagulopathy: can induce blood clots
67
What are the effects of anemia on the circulatory system?
```
• Anemia leads to
↓ blood viscosity leads to
↓ resistance leads to
↑ blood flow leads to
↑ cardiac output
```
```
• Anemia leads to
↓ oxygen transport leads to
↑ hypoxia leads to
↑ vasodilation leads to
↑ blood flow leads to
↑ cardiac output (3-4x normal) leads to
↑ ↑ pumping workload of the heart (can cause heart failure in the long run)
```
68
An anemic person doesn't have much CO reserve, so when O2 demand is increased during exercise, this may lead to
Extreme tissue hypoxia and acute cardiac failure
69
Reduced viscosity as a result of anemia will increase Reynold's number, which will increase the likelihood of ___-
Turbulent flow
70
Effects of polycythemia on the circulatory system
* Increased viscosity leads to
* Decreased flow (sluggish) leads to
* Decreased venous return (VR)
* Polycythemia leads to
* Increased blood cells(increases VR) leads to
* Increased blood volume leads to
* Increased VR
* Both will balance each other out leading to Normal cardiac output
(HTN can develop beyond these limits)
71
Why do neutrophils phagocytes in early inflammation?
So they can ingest and destroy different bacteria and other foreign particles
72
Eosinophils ingest ____, are induced by ____ and increase in ____
Eosinophils ingest antigen-antibody, are induced by IgE hypersensitivity(an antibody) and increase in parasitic infections
73
Basophils are structurally and functionally similar to ___, which is another type of WBC, thought to be a subset of basophils, but has its own cell lineage. Basophils play an important role in ___
Mast cells.
| Play an important role in inflammation
74
___ WBCs attack large parasite, by recognizing it and killing it by secreting various toxic molecules
Eosinophils
75
Granulocytes and monocytes develop in the ___ and mostly remain there until they are needed, when they are then released and secreted into the blood
Bone marrow
76
Lymphocytes develop mostly i the ____, especially ____
Develop mostly in the peripheral lymphoid organs(thymus, spleen, tonsils, lymph nodes, peyer's patches), especially the T-cells
77
Megakaryocytes are where ____ derive from, and they are developed and reside in the ____
Where platelets derive from and are developed and reside in the marrow
78
What is the lifespan of a circulating granulocyte and one in the tissues?
- Circulating: 4-8 hours
- In the tissues: 4-5 days, unless in the presence of an infection, lifespan reduces as a result of phagocytoses, causing them to weaken
79
What is the lifespan of a circulating monocyte/ macrophage and one in the tissues?
Circulating: 10-20hours
| Monocytes develop later once they're in the tissue, as tissue macrophages, it could last for months or longer
80
Lifespan of lymphocytes
Continuously re-circulated: lymph... nodes.... blood.
Long lived
81
____ are replaced every 10 days
Platelets
82
____ are mature cells (once they're in the blood) that can respond immediately to an infection
Neutrophils
83
____ mature in the tissues to become macrophages. When they can then undergo normal function
Monocytes
84
Both neutrophils and monocytes exhibit ___. And what kind?
Motility
• Diapedesis: squeeze through endothelial cells and exit the vessel
• Ameboid motion
• Chemotaxis (Chemoattractants:
bacterial or tissue degradation
products, complement fragments, other chemical mediators) things that attract monocytes and neutrophils
85
What is chemotaxis and what is so special about it?
A cell movement in a direction controlled by a gradient of a diffusible chemical. This is what allows neutrophils to specify the direction to move in
86
What moves cells
Actin
87
What is phagocytosis?
The ingestion of particles, a very important function of neutrophils and macrophages
88
Phagocytes must distinguish between ___ and ___
Must distinguish between foreign particles( that needs to be killed and digested) and host tissues (should not be digested)
89
What features are approriate phagocytic targets?
• May have rough surfaces
• Lack protective protein coats
• May be immunologically marked for phagocytosis by antibodies or complement
components that are recognized by receptors on the phagocytes
90
The immunologic marking for phagocytosis by antibodies is called...?
Opsonization
91
Which phagocyte can ingest more and larger particles and bacteria?
Macrophages
92
____ can extrude digestion products and survive function for many months
Macrophages, unlike neutrophils
93
What happens if a pathogen is too large to be ingested?
Neutrophils can eject a large part of their chromatin(DNA) along side other molecules(which causes death), which will form a sticky web that entraps nearby bacteria, giving other neutrophils and macrophages enough time to come in
94
Once a particle has been ingested, how is it digested?
In both neutrophils and macrophages, phagosomes fuse with lysosomes and other granules to form phagolysosomes (digestive
vesicles).
They contain proteolytic enzymes and in macrophages lipases (imp. in killing tuberculosis bacillus and other bacteria)
95
How else can bacterial be killed if they're not digested?
Enzymes in the phagosome or in peroxisomes generate strongly bactericidal reactive oxygen species such as
• Superoxide (O2)
• Hydrogen peroxide (H2O2)
• Hydroxyl ions (OH)
• Hypocholrite (HOCL) [active ingredient in bleach]
96
What forms the reticuloendothelial system?
Circulating monocytes, mobile macrophages, fixed tissue macrophages, and some specialized endothelial cells
97
What do histocytes do?
They are monocyte-macrophages found in the skin
98
Lymph nodes ingest/sample particles arriving through the ___
Lymph. (this is where everything in the interstitial fluid is pulled back into the circulation)
99
Alveolar macrophages digest/entrap ____
Inhaled particles and microorganisms
100
What does kupffer cells do?
Surveillance of the portal circulation (in the liver, bcos that's where you detoxify anything from the blood)
101
What do macrophages in the spleen and bone marrow do?
Surveillance of the general circulation
102
What is hemostasis?
The prevention or arrest of blood loss
103
What is the mechanism of hemostasis?
1. Vascular constriction
2. Formation of the platelet plug
3. Blood coagulation (formation of the blood clot)
4. Fibrous organization or dissolution of the blood clot
104
Immediately after a vascular trauma, the vascular smooth muscle cells (VSMC) ____
contract to reduce blood flow from the injured vessel
105
Where does the VSMC contraction occur from?
1. Local myogenic spasm
2. Local autacoid factors from tissues and platelets
3. Nervous reflexes
4. Smaller vessels: Thromboxane A2 released
from platelets
106
Wha stimulates the SMC contraction?
Endothelin that is released from the endothelial cells
107
What are the characteristics of platelets?
• Contractile capabilities, because of contractile proteins:
actin, myosin, thrombosthenin
• Residual ER and Golgi: synthesize enzymes,
prostaglandins, fibrin-stabilizing
factor, PDGF, store Ca++
• Mitochondria/ enzymes:
produce ATP, ADP
108
What is contained in the platelet membrane and what are their functions?
```
• Surface glycoprotein(coat of the membrane)
- Repels intact endothelium
- Adheres to injured
endothelium and exposed
collagen
• Membrane phospholipids
- Activate blood clotting
```
109
How is the platelet plug formed (platelet activation)?
* Adhesion to damaged vascular wall
* Platelet degranulation (release their content)
• Aggregation as platelet–vascular wall and platelet-platelet adherence
increases (build up of platelets on the site of injury)
• Activation of the clotting system and development of an immobilizing meshwork of platelets and fibrin
110
At the end of the coagulating cascade, ___ is going to be formed. This is going to form a meshwork that is going to trap platelets and other cells that is going to create the core of the clot
Fibrin
111
Is blood clot formation faster in a severe vascular trauma or in a minor trauma?
A severe vascular trauma
112
Timeline for events in blood clot formation
• Begins in 15- 20 secs in severe vascular trauma
• Occlusive clot within 3-6 mins unless very large vascular
defect
• 20-60 minutes: Clot retraction (kicks out any plasma or serum remaining, to have a tight clot and prevent blood from leaking out)
• 1- 2 weeks
• Invasion by fibroblasts
• Organization into fibrous
tissue (may have scarred tissue)
113
What is the blood clotting mechanism?
When there's an injury you get exposure of blood to the outside and it starts to leak. There are 2 main clotting pathways.
Extrinsic pathway and an intrinsic pathway. Both of their end result will be the activation of the prothrombin activator. Prothrombin activator is going
to act on a plasma protein called prothrombin. Prothrombin is going to turn into Thrombin by the action of prothrombin activator and the presence of Ca2+.
Thrombin is going to act on another plasma protein called fibrinogen, converting fibrinogen into fibrin monomers. Fibrin monomers are going to polymerize and
make threads and enlarged fibers that are going to create the meshwork, the frame work of trapping other cells and forming the core of the blood clot. As we start to have more and more fibrin we're able to trap more and more cells and actually create that blood clot.
114
The rate-limiting factor in blood coagulation is the formation of
____ (most important clotting factor)
prothrombin activator
115
Where is prothrombin formed?
In the liver
116
How can liver disease cause edema?
We don't have plasma proteins and plasma proteins are important for the colloid osmotic pressure of the capillaries.
117
What is a consequence of losing plasma protein formation?
We won't have prothrombin and this is going to
| make us more susceptible to bleeding, hemorrhage and blood loss
118
____ is required by the liver for normal activation of
| prothrombin – as well as other clotting factors.
Vitamin K
119
___is formed in the liver, has a large molecular size, and thus does not leak out into the
interstitial space under normal conditions, unless capillary permeability increases & will causes clotting in the interstitial space
Fibrinogen
120
How is fibrogen (the substrate of thrombin) converted to fibrin?
* Thrombin(weak protease) cleaves four small peptides from fibrinogen → fibrin monomer → spontaneous polymerization (attach together to form):
* Long fibers which form clot reticulum (each fiber is held on to the next by weak H+ bonds)
121
Because the long fibers that form the clot reticulum is held together by weak H+ bonds, there is a need to stabilize them using ____. How does this stabilizer work?
* Fibrin stabilizing factor
* In plasma and released from platelets
* Activated by thrombin
* Covalent cross-linking of fibrin monomers and adjacent fibrin fibers, which stabilizes the clot
122
How is the clot extended?
* Thrombin is bound to platelets and trapped in the clot
| * The clot acts on prothrombin to generate more thrombin (positive feedback, this is how the clot extends)
123
Thrombin produces more prothrombin activator by acting on ___
other clotting factors
124
Additional fibrin monomers and polymers are generated at the ___
periphery of the clot
125
How fast does clot retraction begin?
Within 20-60 mins
126
In clot retraction ___ binds to damaged vessel wall
Fibrin
127
In clot retraction, platelets bind to ___ and contract via actin, myosin, thrombosthenin
Multiple fibrin fibers
128
In clot retraction, the clot __
Clot tightens, expressing serum, and closing the vascular defect
129
During the formation of prothrombin activator, the intrinsic pathway is activated when ___
When blood is exposed to collagen, the factor XII is going to be activated and its going to start the intrinsic pathway
to produce prothrombin activator
130
During the formation of prothrombin activator, the extrinsic pathway is activated when ___
When the vessel is damage the endothelial cells are going to release a clotting factor called tissue factor (TF). TF is the initiation point of the extrinsic pathway that is going to follow then eventually give us prothrombin activator
131
Under normal conditions, intrinsic and extrinsic pathways work __
together
132
Which pathway is faster, intrinsic or extrinsic?
Extrinsic
133
What are the mechanisms that prevent our blood from clotting in our vessels under normal conditions?
* Smoothness of the endothelial surface
* Mucopolysaccharide coating (glycocalyx)
* Thrombomodulin bound to endothelium binds(competes for) thrombin
* Damage to glycocalyx
134
How does the smoothness of the endothelial surface prevent our blood from clotting in our vessels under normal conditions?
Prevents the platelets from attaching to the surface and if cannot attach, they cannot aggregate and if they cannot aggregate they cannot form the blood clot
135
How does the Mucopolysaccharide coating (glycocalyx) prevent our blood from clotting in our vessels under normal conditions?
Repels platelets and clotting factors, they also cannot adhere and attach to the endothelial surface
136
___ is known to destroy the glycocalyx
Smoking
137
How does the thrombomodulin bound to endothelium binds(competes for) thrombin prevent our blood from clotting in our vessels under normal conditions?
to prevent it from converting fibrinogen to fibrin; once it attaches to the thrombin it forms a thrombin-thrombomodulin complex
138
What does the thrombin-thrombomodulin complex do?
Thrombin-thrombomodulin activates Protein C→ inactivates factors V and VIII, which are clotting factors that are essential for the blood clot to form
139
How does the Damage to glycocalyx prevent our blood from clotting in our vessels under normal conditions?
activates factor XII,
| platelets (intrinsic pathway). If collagen is exposed→ even more robust
140
What removes thrombin from the blood?
Fibrin and antithrombin III
141
Why do fibrin fibers (which gives us a form of negative feedback) bind 85-90% of thrombin and localize it to the clot?
So that the thrombin doesn't move anywhere and form a clot elsewhere
142
What does antithrombin III do?
its going to inactivate any thrombin that drifts away from the sit of the clot; inactivate any thrombin that fibrin cannot bind to and localize
143
Fibrin and antithrombin III are _____
Intravascular Anticoagulants
144
Characteristics of Intravascular Anticoagulants - Heparin
• Physiologically, availability is limited
• Used therapeutically
• Highly negatively charged
• Binds anti-thrombin III and increases its effectiveness 100- 1000-fold
• Heparin-antithrombin III removes free thrombin from the blood almost instantly
• Also removes XIIa, XIa, Xa, and IXa
• Mast cells, basophils particularly abundant in pericapillary regions of liver
and lung
145
Heparin has an ___ effect. How does it act?
Indirect. It acts through enhancing the effectiveness of anti-thrombin III
146
What is the fibrinolytic system for?
When the tissue or vessel is healed we need to be able to
break the clots and prevent the clot from continuing formation which means if plasmin is introduced at the time of the clot it can stop the clot and break it down
147
Mechanism of the fibrinolytic system
• Plasminogen is trapped in the clot
• Over several days, injured tissues release tissue plasminogen activator (tPA)
• Plasminogen is activated to
plasmin, a protease resembling trypsin
• Plasmin digests fibrin fibers and several other clotting factors
• Often results in re-opening
repaired small blood vessels
148
____ is used clinically to activate plasminogen
| convert it to plasmin and break down a clot
t-PA
149
What are the conditions of the inability to stop bleeding?
1. Liver disease – deficiency of any of the clotting factors
2. Vitamin K deficiency (product of liver disease)
3. Hemophilia
4. Thrombocytopenia (platelet deficiency)
150
What are the factors that can cause Vitamin K deficiency?
* Produced in the intestine by bacteria (forms of GI diseases that destroy the bacteria in our intestine or strong antibiotics administered for a long time to kill the antibiotics)
* Fat-soluble: malabsorption of fats
* Lack of bile production or delivery can cause fat malabsorption
151
Why do patients with liver or biliary disease need a vitamin K injection 4-8hrs before surgery?
so that these patients have clotting factors in their system in order to be able to clot and stop excessive bleeding
152
What is hemophilia A and B.
- Hemophilia A: Deficiency of factor VIII (more common)
| - Hemophilia B: Deficiency of factor IX (called the christmas factor)
153
Both types of hemophilia impair ___ pathway activation
Intrinsic pathway activation (This is a case where you have the extrinsic pathways is still working but the intrinsic pathway is not)
154
Why does hemophilia mainly occur in males?
Because they are both on the X-chromosome, and males only have one, compared to females
155
What does hemophilia look like clinically?
Bleeding after minor trauma
156
What is thrombocytopenia?
a condition where we have a decrease in the platelet count
157
A platelet count of <50,000/mm3 is as a result of ___
hemorrhage from minor trauma
158
A platelet count of <15,000/mm3 is as a result of ___
spontaneous bleeding
159
A platelet count of <10,000/mm3 is as a result of ___
severe bleeding
160
What are the causes of thrombocytopenia?
• Hypersplenism
• Autoimmune disease
• Hypothermia
• Viral or bacterial infections that cause disseminated intravascular coagulation (DIC)
• Heparin-induced thrombocytopenia (HIT)
§ IgG antibodies target heparin-platelet factor 4 complex
§ Typically causes 50% drop in platelet count
161
Thrombocytopenia manifests into...
- Tendency to bleed from small venules or capillaries (because the platelet plug is usually the only thing that can stop bleeding in small vessels)
- Petechiae
- Purpura
162
What is petechiae?
```
are minute (1 to 2 mm in diameter) hemorrhages into skin, mucous membranes, or serosal surfaces. Causes
include low platelet count
(thrombocytopenia) and defective platelet function.
```
163
What is Purpura?
```
slightly larger (3 to 5 mm) hemorrhages. Purpura can result from the same disorders that cause petechiae, as well as trauma, vascular inflammation (vasculitis), and increased vascular
fragility
```
164
An abnormal clot is called a ____
Thrombus
165
A floating clot is called an ____
Embolus
166
What are the 2 thromboembolic conditions?
Thrombus or embolus
167
Thromboembolic conditions are caused by...?
• Endothelial roughening (e.g. atherosclerosis)
• Slow flow (e.g. prolonged air
travel)
168
How are thromboembolic conditions treated?
* tPA
| * Embolectomy
169
What is pulmonary embolism?
When you have a clot that travels up the veins to the heart through the right atrium and ventricle and as it goes up the veins get larger. It develops in the veins but it's not going to encounter small vessels until it reaches the pulmonary artery
170
Pulmonary embolism usually comes from ___. Treated by...
Deep leg veins.
Treated by tPA
171
Disseminated intravascular coagulation occurs in ____
Occurs in the setting of massive tissue damage or sepsis
172
Disseminated intravascular coagulation is a ____, that can be hard to control decreasing the delivery of O2 and other nutrients that we need and therefore causing septicemic shock
Wide-spread coagulation in
| small vessels
173
Disseminated intravascular coagulation is manifested as....
Manifested as bleeding from
multiple sites because of
depletion of clotting factors
174
Which blood coagulation test is used most often? And how is it done?
Prothrombin time
• Add excess calcium and tissue factor to oxylated blood,
measure time to clot
• Assesses Extrinsic and Common Pathways
• Usually about 12 seconds
• Tissue factor batches have to be standardized (activity expressed as “International Sensitivity Index (ISI)” )
175
What is the international normalized ration (INR) and why was it created?
Devised to standardize measurements of Prothrombin test and it was created because different testing procedures across different labs can produce different prothrombin times
176
What are the 1st, 2nd, and 3rd line of defense in resistance to infection?
```
• First line of defense
• Innate (natural, native)
immunity
• Physical, mechanical,
biochemical barriers
• Second line of defense
• Inflammation (innate/natural)
• Third line of defense
• Adaptive (acquired)
(specific) immunity
```
177
What are the first line of defense and what do they do?
- Physical barriers that limit microbial infection
- Skin
- Linings of the
gastrointestinal,
genitourinary, and
respiratory tracts
- Epithelial cell-derived chemical barriers
- Secrete saliva, tears,
earwax, sweat, and mucus
- Antimicrobial peptides
- Normal microbiome
178
What is included in the Linings of the gastrointestinal, genitourinary, and respiratory tracts of the 1st line of defense?
* Sloughing off of cells
* Coughing and sneezing
* Flushing—urine
* Vomiting
* Mucus and cilia
179
The epithelial cell-derived chemical barriers secretion of saliva, tears, earwax, sweat and mucus does what?
It provides a barrier of protection
180
The epithelial cell-derived chemical barriers antimicrobial peptides does what?
Kill bacteria upon contact.
181
What are the antimicrobial peptides?
Cathelicidins, defensins, collectins, and mannose-binding lectin
182
What does the normal microbiome do for the 1st line of defense?
Each surface colonized by bacteria and fungi that is unique to the particular location and individual provides helpful service
183
The inflammatory response of the 2nd line of defense is a ____ response. It is caused by a variety of materials like___and its local manifestations are the 5 cardinal signs of inflammation.
The inflammatory response of the 2nd line of defense is a *nonspecific* response. It is caused by a variety of materials like *infection, tissue necrosis, trauma, physical or chemical injury, foreign bodies, immune reaction, or ischemia* and its local manifestations are the 5 cardinal signs of inflammation
184
What are the 5 cardinal signs of inflammation
- Redness
- Heat
- Swelling
- Pain
- Loss of function
185
What are the vascular responses of the inflammatory response in the 2nd line of defense?
* Blood vessel dilation (leads to inc. blood flow and leakage into the interstitial space)
* Increased vascular permeability and leakage of fluids and plasma proteins through the capillaries, inc. intersitial colloid osmotic pressure, leads to edema development
* White blood cell adherence to the inner walls of the vessels and migration through the vessels. WBC migrate to tissue spaces
186
What are the goals of inflammation?
* Prevent and limit infection and further damage
* Initiate adaptive immune response
* Initiate healing
* limit and control inflammatory process
187
When are plasma protein systems activated?
Activated during inflammatory response to help WBCs and immune cells do their job
188
What does plasma protein system: complement system do?
Activates 20 proteins through 3 different pathways to increase phagocytosis. This
- Kills bacteria
- Assist with neutrophil migration
- Stimulate mast cells to release histamine
- Increase inflammatory response
189
What does plasma protein system: clotting system do?
Blood clot reduces blood flow and controls inflammatory response
- Inc. permeability: allows more WBCs to enter and exit the tissue
- Inc. neutrophil migration through chemotactic factors and through inc perm.
190
What does plasma protein system: Kinn system do?
Produces histamine like effects that increases permeability and stimulate nerve endings, producing pain
191
What does "walling-off" sites of inflammation mean?
When fibronogen clots minimizes fluid flow in and out of the inflamed area. This controls inflammatory response and confines bacteria/prevents spreading
192
____ causes intense inflammation and are effectively walled-off, as opposed to ___, which doesn't and can lead to death
Staphylococci
| Streptococci
193
____ that encounter foreign particles enlarge and become mobile to provide a first line of defense, through phagocytosis
Tissue macrophages
194
Within an hour neutrophils migrate to the area in response to ____, which is secreted by tissue macrophages and cells
inflammatory cytokines (TNF, IL-1)
195
Upregulated selectins and ICAM-1 on endothelial cells are bound by integrins on neutrophils, leading to margination, followed by
____ directing neutrophils into the inflamed tissues, to kill bacteria and scavenge
diapedesis, and chemotaxis
196
At sites of injury or inflammation, ___ is released, and __ cells are stimulated. These cells secrete ___, a surface protein which binds to carbohydrates on ____, causing WBCs to stick to blood vessel walls
At sites of injury or inflammation, *cytokines* is released, and *endothelial* cells are stimulated. These cells secrete *selectins*, a surface protein which binds to carbohydrates on *leukocytes*, causing WBCs to stick to blood vessel walls
197
There is a ___ binding affinity between leukocytes and selectin, so leukocyte rolls along until it exits between ____ found without disrupting vessel walls and travel within the ____.
There is a *low* binding affinity between leukocytes and selectin, so leukocyte rolls along until it exits between *endothelial cells* found without disrupting vessel walls and travel within the *connective tissue*.
198
Integrins are on ___ and selectins on ____. Neutrophil roll on endothelial surface from the interaction of ___ with ___
Integrins are on *WBCs* and selectins on *endothelial cells*. Neutrophil roll on endothelial surface from the interaction of *integrins* with *selectins*
199
In response to ___ monocytes gradually accumulate
| and become macrophages
Chemoattractants
200
In part due to increased bone marrow production, __ become the dominant inflammatory cell
macrophages
201
Growth factors produced in response to infection and inflammation drive proliferation
and differentiation of ___in the marrow
leukocyte precursors
202
The bone marrow can increase production of ____by 20 – 50 fold and maintain this for months or years
neutrophils and monocytes
203
What is pus composed of?
Pus is composed of dead bacteria and neutrophils, many dead macrophages, necrotic tissue that has been degraded by proteases, and tissue fluid, often in a cavity formed at the inflammatory site
204
Usually pus is absorbed by ___, but if the infection overwhelms this system, pus will accumulate and grow
The lymphatic system
205
What two cell types release heparin, histamine, bradykinin and serotonin?
Basophils and mast cells
206
When IgE bound to receptors on their surfaces is cross-linked by its specific antigen, ___ degranulate, releasing inflammatory mediators:(histamine, bradykinin, serotonin, heparin, leukotrienes, and several lysosomal
enzymes) that produce inflammatory response, namely ____ and ____
When IgE bound to receptors on their surfaces is cross-linked by its specific antigen, *mast cells and basophils* degranulate, releasing inflammatory mediators:(histamine, bradykinin, serotonin, heparin, leukotrienes, and several lysosomal enzymes) that produce inflammatory response, namely *vasodilation* and *Inc. permeability*
207
What is the role of IgE in histamine release?
IgE (antibody) binds to receptor, picks up and cross links with antigen, then mast cells degranulate and release histamine, then inflammatory response begins. (this is how allergic reactions start)
208
What is the role of basophil and mast cells?
To initiate and maintain inflammatory response through attracting various cells and initiating and maintaining vascular response
209
What is leukopenia and how does it happen?
Leukopenia, or low white blood cell count, is usually the result of reduced production of cells by the bone marrow
210
What happens within two days of bone marrow shut down?
mucous membrane ulcers or
| respiratory infection may occur
211
What are the causes of leukopenia?
radiation, chemical toxins, some medicines or anything affecting bone marrow production
212
What is leukemia?
Uncontrolled production of abnormal white blood cells due to a genetic mutation
213
What are the cancer routes of leukemia?
Lymphocytic vs. myelogenous
214
Types of leukemias get their names from...?
The type of cells that is affected
215
What are the clinical effects of leukemia?
• Growth of leukemic cells in abnormal sites
• Invasion of bone from the marrow, with pathologic fractures
• Eventually spreads to vascular and lymphatic “filters”… spleen, lymph
nodes, liver, other organs
• Replacement of normal bone marrow, resulting in infection, and bleeding
• Wasting because of metabolic demands (due to high production of immature cells)
216
How do cytotoxic T cells kill bacteria?
T-cells bind to invader cell and inserts bactericidial agents into it
217
Helper T cells are __% of T cells and they regulate ___
75%, and they regulate functions of other immunologic cells by producing cytokines (IL-2-6, GM-CSF, and interferon-gamma)
218
TH1 activates ___
Activates macrophages, cytotoxic T cells, and B cells
219
TH2 activate __
Only B cells
220
How do T-cells help the immune system?
- Positive feedback for helper T cells (IL-2)
- Stimulation of cytotoxic T cells (IL-2, other cytkines)
- Stimulation of B cells (IL-4-6, (BCGFs))
- Macrophage accumulation, activation, enhanced killing
221
Why are Helper T cells essential?
They are essential, because they pick up antigens, activate B cells that secrete IgM, IgG..., activate other T cells, regulates and mediates response by producing cytokines
222
T cells are encoded by ___
Major Histocompatibility Complex (MHC)
223
MHC I present to ___
cytotoxic T cells (CD8)
224
MHC II present to ____
helper T cells (CD4)
225
Binding of antigen to MHC proteins increases the likelihood ___ will pick up the foreign protein fragment and activate
T-cell
226
What are the two ways that T cells respond differently from B cells?
1. T- cells are activated by the foreign antigen only when the antigen is displayed on antigen
-presenting cells (APC). The form of antigen that a T-cell can recognize is different
than what the B-cell can recognize. B-cells can
recognize intact protein antigens, but T-cells
can only recognize fragments of protein antigens that have been partly degraded. MHC proteins bind with these fragments and carry them to the surface of the APC.
2. Once activated, effector T cells act only at short range, within secondary lymphoid
organs or after migration. (unlike B cells, who release antibodies that travel throughout the body)
227
____ binds with antigen fragments and present them on cell surface
MHC protein
228
The complement system is made up of 20 proteins that are made in the ___ and circulate the __ and ___
The complement system is made up of 20 proteins that are made in the *liver* and circulate the *blood* and *ECF*
229
What are the 3 pathways in the complement system?
- Classical pathway
- Lectin pathway
- Alternative pathway
230
The early component of all 3 pathways in the complement system is to ___
Activate C3
231
What is the function of C3?
- Induce phagocytosis
- Break down or create pores within the pathogen's membrane
- Stimulate adaptive immune response by activating T or B cells
- Recruit inflammatory cells
- Important for bringing immune cells whether adaptive or innate immune cells to the site of the problem and for the cells to start killing invaders
232
People with ____ deficiency are subject to repeated bacterial infections
People with C3 deficiency
233
Cleavage of each ___ activates the next component leading to an amplifying cascade in the complement system
Proenzyme
234
What are the two things that many cleavages in the complement system liberate?
1. Small active peptide fragments that can attract phagocytes
2. Large membrane- binding fragments
235
The binding of the membrane fragments to the next surface of a pathogen helps carry out the next reaction in the sequence of the complement system which is ___
Making the complement system confined to the particular cell surface where it began
236
What are the classes of antibodies?
* IgM (earliest produced, five pairs of heavy chains and light chains)
* IgG (75% of all immunoglobulins)
* IgA
* IgD
* IgE (critically involved in allergic reactions)
237
What is the mechanisms of action of antibodies?
* Agglutination
* Precipitation
* Neutralization
* Lysis
* Complement activation
238
What is agglutination?
When antibodies to antigen and clump together
239
Where is precipication found?
Found in the blood and it also inactivates antibodies
240
What is neutralization?
When antibodies bind to specific active sites on the pathogen or antigenic agent
241
What is lysis?
The binding of antibodies initiates breakdown of pathogens
242
Antibody production consist of...
• B cells bind intact antigen
• T cells bind presented antigenic peptides
• B cells proliferate (with T cell help), developing lymphoblasts and
plasmablasts
• Up to 500 antigen-specific progeny in 4 days, each producing as many as 2,000Ig molecules/sec
• Can persist for many weeks, if antigenic stimulation persists
243
Antibody specificity is when each antibody has __
a steric configuration specific to its antigen
244
Multiple prosthetic groups of each antigen interact with complementary structures of the antibody, through…
* hydrophobic bonding
* hydrogen bonding
* ionic interactions
* van der Waals forces
245
Antibodies are at least ___
bivalent
246
___ produces a greater and stronger immune response
Second exposure to anitgens
247
Antibodies can inactivate ___ and ____ by binding to them
Inactivate viruses and microbial toxins by binding to them
248
Once bound, antibodies can help recruit components of the ___
innate immune system
249
Antibodies are exclusively synthesized by ___
B-cells
250
___ are the most abundant proteins in the blood
Antibodies
251
What is an autoimmune disorder?
when our bodies are producing antibodies that are killing
our own cells because the capability of immunological self tolerance for one reason or the other is no longer acting properly. (when mechanisms of immunological self tolerance are not working properly)
252
Examples of autoimmune disorders
* Rheumatic fever (cross-reactivity with streptococcal antigens)
* Post-streptococcal glomerulonephritis
* Myasthenia gravis (antibodies to acetylcholine receptors)
* Systemic lupus erythematosus (auto-immunity to multiple tissues)
253
What is the mechanism of immunological self-tolerance (that filter good lymphocytes from bad ones)?
1. Receptor editing (central lymphoid organ)
2. Clonal deletion (central lymphoid organ)
3. Clonal inactivation (peripheral lymphoid organ)
4. Clonal suppression (peripheral lymphoid organ)
254
If a defective lymphocyte passes from the central lymphoid organ, the body is unable to edit its receptor, instead the body will ___
Delete, inactivate, or suppress the entire colony.
255
What suppresses a lymphocyte in the peripheral lymphoid organ?
Regulatory T-cell
256
What do helper T cells activate?
- Other killer T cells
- B cells
- Macrophages that secrete cytokines that promote lymphocyte growth and differentiation
257
Both B and T cells require ____ to proliferate
Antigenic stimulation
258
What do macrophages do for lymphocyte activation?
* ingest antigen and present antigenic peptides on the cell surface to “helper” T cells
* Secrete IL-1, other cytokines that promote lymphocyte growth and differentiation (example of adaptive and acquired immune system working together)
259
The acquired immune system works by ___
Clonal selection
260
How does the clonal selection theory work?
1. Random generation of diverse lymphocytes
2. As each lymphocyte develops in a central
lymphoid organ, it becomes committed to react with a specific antigen before actually
being exposed to the antigen
3. When the lymphocyte comes in contact with
the antigen at the peripheral lymphoid organ, the binding of the antigen drives further
proliferation – clonal expansion
4. The encounter also causes the cells to differentiate into effector cells
5. This makes the acquired immunity antigen-specific
261
Where does the T- lymphocyte differentiate/ develop?
In the thymus
262
Hemopoietic stem cells can become __ progenitor cells or ____ progenitor cells
Common lymphoid progenitor cells or common myeloid progenitor cells
263
B cells develop/ differentiate in the ___
Bone marrow
264
___ mediate acquired immunity
Lymphocytes
265
Lymphocytes are called ___ or ___ organs
Primary or central lymphoid organ
266
Newly formed lymphocytes migrate from the ___ organs to the ___ organs
From the central organs to the peripheral organs
267
What is an antigen?
A substance that can elicit an immune response
268
The surface of each invading organism has a unique ___ that is made up of proteins or polysaccharides
Antigen
269
What is an epitope?
The molecular structures that are specifically recognized in acquired immunity
270
Once antigens are recognized by the immune system, the immune cells are ____
Activated and then can carry on with their effect
271
What are antibodies?
activated cells that specifically target and destroy invading organisms and toxins
272
What are the two types of acquired immunity?
Humoral (B cells)
| Cell- mediated (T cells)
273
The action of acquired immunity is performed through ___
Antibodies produced by B cells or Killer T cells that kill pathogens directly
