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Flashcards in Test 3 week 6 Deck (273)
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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
Q

Once RBCs are worn out what happens to them?

A

They are phagocytosed and digested by macrophages in the liver and spleen

26
Q

What happens to hemoglobin transport if its not kept inside the RBC?

A

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
Q

____ contain large quantities of the enzyme carbonic anhydrase, which aids in the transport of CO2

A

Erythrocytes/ RBCs

28
Q

What are the 3 forms that CO2 is transported?

A
  • 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
Q

Why is the biconcave disk shape of an RBC important?

A

It is optimal for the RBC to be able to squeeze through tight and narrow passages in the circulation

30
Q

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

A

Spleen

31
Q

There are more RBCs in a healthy ___, than in a healthy ___. And they can hold more hemoglobin

A

There are more RBCs in a healthy men, than in a healthy women

32
Q

The ability of bone marrow to produce RBCs ___ with age

A

Reduce

33
Q

RBCs are generated from ___, because they make up a tiny portion of the bone marrow population

A

Stem cells

34
Q

Which cells are not developed in the bone marrow?

A

T- lymphocytes(thymus), macrophages and osteocytes (monocytes)

35
Q

What is a colony stimulating factor (CSF)?

A

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
Q

What does erythropoietin (EPO) do as a CSF and where is it produced?

A

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
Q

If there is a high concentration of granulcytes (CSF), the myeloid progenitor are going to pick a path to produce ___

A

WBCs

38
Q

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)

A

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
Q

What happens when both of a person’s kidneys have been removed?

A

The person becomes anemic due to EPO loss

40
Q

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

A

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
Q

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

A

Exercise increase RBCs production, until it hits a plateau, where plasma volumedecreases. This is then compensated by an increase in RBC volume and the lasting effect is an increase in total blood volume

42
Q

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

A

Vitamin B12 and Folic acid

43
Q

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

A condition called macrocytic anemia

44
Q

What causes pernicious anemia?

A

Vitamin B12 deficiency

45
Q

How does pernicious anemia occur?

A
  • 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
Q

Pernicious anemia can also occur as a result of ___deficiency

A

folic acid

47
Q

What does macrocytic normochromic anemia mean?

A
  • 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
Q

What is bilirubin, where and how is it formed, and where is it secreted?

A
  • 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
Q

What happens when the content of bilirubin increases greatly?

A

Jaundice

50
Q

What causes an increase in bilirubin?

A

An increase in RBC degradation or obstruction in bilirubin secretion in the bille

51
Q

What are the 2 types of jaundice caused by an increase of bilirubin?

A
  • 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
Q

How much iron is required daily for RBC generation? And where does it come from?

A

25 mg.

1-2 are used from diet, the rest is from recycling RBCs

53
Q

What are ways to lose iron?

A
  • Sweat
  • Urine
  • Bile
  • Minor bleeding
54
Q

67% of total body iron is bound to ____

A

heme in RBCs and muscle cells (myoglobin)

55
Q

30% of iron is stored in ___ and ____

A

In macrophages and hepatic paranchymal cells

56
Q

What king of anemia does iron deficiency lead to? And what does it mean?

A

Microcytic-Hypochromic Anemias

  • Microcytic: cells are smaller in size
  • Hypochromic: Hemoglobin content is decreased, so cells don’t have their normal colors
57
Q

What disorders are related to Microcytic-Hypochromic Anemias and why?

A
  • 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
Q

What is normocytic-normochromic anemia and what causes it?

A

Normal sized and normal hemoglobin content RBCs.

Caused by a deficiency in the total amount of RBCs present in the body

59
Q

What are the factors that can cause a deficiency in the total amount of RBC in the body?

A
  • 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
Q

What are the types of myeloproliferative RBC disorders?

A
  • Polycythemia
  • Relative polycythemia
  • Absolute polycythemia
  • Polycythemia vera
61
Q

What causes polycythemia?

A

Overproduction of red blood cells

62
Q

What causes relative polycythemia?

A
  • 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
Q

What are the two types of absolute polycythemia and what causes them?

A
  • 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
Q

What is polycythemia vera JAK2 mutation?

A

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
Q

What is polycythemia vera and what causes it?

A

An abnormal, uncontrolled proliferation of RBCs, WBCs, and platelets. Manifests as a result of increased RBC mass and hematocrit.

66
Q

Polycythemia vera leads to…

A
  • Increased blood viscosity(as a result of increased RBC mass)
  • Hypercoagulopathy: can induce blood clots
67
Q

What are the effects of anemia on the circulatory system?

A
• 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
Q

An anemic person doesn’t have much CO reserve, so when O2 demand is increased during exercise, this may lead to

A

Extreme tissue hypoxia and acute cardiac failure

69
Q

Reduced viscosity as a result of anemia will increase Reynold’s number, which will increase the likelihood of ___-

A

Turbulent flow

70
Q

Effects of polycythemia on the circulatory system

A
  • 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
Q

Why do neutrophils phagocytes in early inflammation?

A

So they can ingest and destroy different bacteria and other foreign particles

72
Q

Eosinophils ingest ____, are induced by ____ and increase in ____

A

Eosinophils ingest antigen-antibody, are induced by IgE hypersensitivity(an antibody) and increase in parasitic infections

73
Q

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 ___

A

Mast cells.

Play an important role in inflammation

74
Q

___ WBCs attack large parasite, by recognizing it and killing it by secreting various toxic molecules

A

Eosinophils

75
Q

Granulocytes and monocytes develop in the ___ and mostly remain there until they are needed, when they are then released and secreted into the blood

A

Bone marrow

76
Q

Lymphocytes develop mostly i the ____, especially ____

A

Develop mostly in the peripheral lymphoid organs(thymus, spleen, tonsils, lymph nodes, peyer’s patches), especially the T-cells

77
Q

Megakaryocytes are where ____ derive from, and they are developed and reside in the ____

A

Where platelets derive from and are developed and reside in the marrow

78
Q

What is the lifespan of a circulating granulocyte and one in the tissues?

A
  • 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
Q

What is the lifespan of a circulating monocyte/ macrophage and one in the tissues?

A

Circulating: 10-20hours

Monocytes develop later once they’re in the tissue, as tissue macrophages, it could last for months or longer

80
Q

Lifespan of lymphocytes

A

Continuously re-circulated: lymph… nodes…. blood.

Long lived

81
Q

____ are replaced every 10 days

A

Platelets

82
Q

____ are mature cells (once they’re in the blood) that can respond immediately to an infection

A

Neutrophils

83
Q

____ mature in the tissues to become macrophages. When they can then undergo normal function

A

Monocytes

84
Q

Both neutrophils and monocytes exhibit ___. And what kind?

A

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
Q

What is chemotaxis and what is so special about it?

A

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
Q

What moves cells

A

Actin

87
Q

What is phagocytosis?

A

The ingestion of particles, a very important function of neutrophils and macrophages

88
Q

Phagocytes must distinguish between ___ and ___

A

Must distinguish between foreign particles( that needs to be killed and digested) and host tissues (should not be digested)

89
Q

What features are approriate phagocytic targets?

A

• 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
Q

The immunologic marking for phagocytosis by antibodies is called…?

A

Opsonization

91
Q

Which phagocyte can ingest more and larger particles and bacteria?

A

Macrophages

92
Q

____ can extrude digestion products and survive function for many months

A

Macrophages, unlike neutrophils

93
Q

What happens if a pathogen is too large to be ingested?

A

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
Q

Once a particle has been ingested, how is it digested?

A

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
Q

How else can bacterial be killed if they’re not digested?

A

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
Q

What forms the reticuloendothelial system?

A

Circulating monocytes, mobile macrophages, fixed tissue macrophages, and some specialized endothelial cells

97
Q

What do histocytes do?

A

They are monocyte-macrophages found in the skin

98
Q

Lymph nodes ingest/sample particles arriving through the ___

A

Lymph. (this is where everything in the interstitial fluid is pulled back into the circulation)

99
Q

Alveolar macrophages digest/entrap ____

A

Inhaled particles and microorganisms

100
Q

What does kupffer cells do?

A

Surveillance of the portal circulation (in the liver, bcos that’s where you detoxify anything from the blood)

101
Q

What do macrophages in the spleen and bone marrow do?

A

Surveillance of the general circulation

102
Q

What is hemostasis?

A

The prevention or arrest of blood loss

103
Q

What is the mechanism of hemostasis?

A
  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
Q

Immediately after a vascular trauma, the vascular smooth muscle cells (VSMC) ____

A

contract to reduce blood flow from the injured vessel

105
Q

Where does the VSMC contraction occur from?

A
  1. Local myogenic spasm
  2. Local autacoid factors from tissues and platelets
  3. Nervous reflexes
  4. Smaller vessels: Thromboxane A2 released
    from platelets
106
Q

Wha stimulates the SMC contraction?

A

Endothelin that is released from the endothelial cells

107
Q

What are the characteristics of platelets?

A

• 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
Q

What is contained in the platelet membrane and what are their functions?

A
• Surface	glycoprotein(coat of the membrane)
    - Repels intact endothelium
    - Adheres to injured 
      endothelium and exposed	 
      collagen
• Membrane	phospholipids
     - Activate blood	clotting
109
Q

How is the platelet plug formed (platelet activation)?

A
  • 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
Q

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

A

Fibrin

111
Q

Is blood clot formation faster in a severe vascular trauma or in a minor trauma?

A

A severe vascular trauma

112
Q

Timeline for events in blood clot formation

A

• 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
Q

What is the blood clotting mechanism?

A

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
Q

The rate-limiting factor in blood coagulation is the formation of
____ (most important clotting factor)

A

prothrombin activator

115
Q

Where is prothrombin formed?

A

In the liver

116
Q

How can liver disease cause edema?

A

We don’t have plasma proteins and plasma proteins are important for the colloid osmotic pressure of the capillaries.

117
Q

What is a consequence of losing plasma protein formation?

A

We won’t have prothrombin and this is going to

make us more susceptible to bleeding, hemorrhage and blood loss

118
Q

____ is required by the liver for normal activation of

prothrombin – as well as other clotting factors.

A

Vitamin K

119
Q

___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

A

Fibrinogen

120
Q

How is fibrogen (the substrate of thrombin) converted to fibrin?

A
  • 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
Q

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?

A
  • 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
Q

How is the clot extended?

A
  • 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
Q

Thrombin produces more prothrombin activator by acting on ___

A

other clotting factors

124
Q

Additional fibrin monomers and polymers are generated at the ___

A

periphery of the clot

125
Q

How fast does clot retraction begin?

A

Within 20-60 mins

126
Q

In clot retraction ___ binds to damaged vessel wall

A

Fibrin

127
Q

In clot retraction, platelets bind to ___ and contract via actin, myosin, thrombosthenin

A

Multiple fibrin fibers

128
Q

In clot retraction, the clot __

A

Clot tightens, expressing serum, and closing the vascular defect

129
Q

During the formation of prothrombin activator, the intrinsic pathway is activated when ___

A

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
Q

During the formation of prothrombin activator, the extrinsic pathway is activated when ___

A

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
Q

Under normal conditions, intrinsic and extrinsic pathways work __

A

together

132
Q

Which pathway is faster, intrinsic or extrinsic?

A

Extrinsic

133
Q

What are the mechanisms that prevent our blood from clotting in our vessels under normal conditions?

A
  • Smoothness of the endothelial surface
  • Mucopolysaccharide coating (glycocalyx)
  • Thrombomodulin bound to endothelium binds(competes for) thrombin
  • Damage to glycocalyx
134
Q

How does the smoothness of the endothelial surface prevent our blood from clotting in our vessels under normal conditions?

A

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
Q

How does the Mucopolysaccharide coating (glycocalyx) prevent our blood from clotting in our vessels under normal conditions?

A

Repels platelets and clotting factors, they also cannot adhere and attach to the endothelial surface

136
Q

___ is known to destroy the glycocalyx

A

Smoking

137
Q

How does the thrombomodulin bound to endothelium binds(competes for) thrombin prevent our blood from clotting in our vessels under normal conditions?

A

to prevent it from converting fibrinogen to fibrin; once it attaches to the thrombin it forms a thrombin-thrombomodulin complex

138
Q

What does the thrombin-thrombomodulin complex do?

A

Thrombin-thrombomodulin activates Protein C→ inactivates factors V and VIII, which are clotting factors that are essential for the blood clot to form

139
Q

How does the Damage to glycocalyx prevent our blood from clotting in our vessels under normal conditions?

A

activates factor XII,

platelets (intrinsic pathway). If collagen is exposed→ even more robust

140
Q

What removes thrombin from the blood?

A

Fibrin and antithrombin III

141
Q

Why do fibrin fibers (which gives us a form of negative feedback) bind 85-90% of thrombin and localize it to the clot?

A

So that the thrombin doesn’t move anywhere and form a clot elsewhere

142
Q

What does antithrombin III do?

A

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
Q

Fibrin and antithrombin III are _____

A

Intravascular Anticoagulants

144
Q

Characteristics of Intravascular Anticoagulants - Heparin

A

• 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
Q

Heparin has an ___ effect. How does it act?

A

Indirect. It acts through enhancing the effectiveness of anti-thrombin III

146
Q

What is the fibrinolytic system for?

A

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
Q

Mechanism of the fibrinolytic system

A

• 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
Q

____ is used clinically to activate plasminogen

convert it to plasmin and break down a clot

A

t-PA

149
Q

What are the conditions of the inability to stop bleeding?

A
  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
Q

What are the factors that can cause Vitamin K deficiency?

A
  • 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
Q

Why do patients with liver or biliary disease need a vitamin K injection 4-8hrs before surgery?

A

so that these patients have clotting factors in their system in order to be able to clot and stop excessive bleeding

152
Q

What is hemophilia A and B.

A
  • Hemophilia A: Deficiency of factor VIII (more common)

- Hemophilia B: Deficiency of factor IX (called the christmas factor)

153
Q

Both types of hemophilia impair ___ pathway activation

A

Intrinsic pathway activation (This is a case where you have the extrinsic pathways is still working but the intrinsic pathway is not)

154
Q

Why does hemophilia mainly occur in males?

A

Because they are both on the X-chromosome, and males only have one, compared to females

155
Q

What does hemophilia look like clinically?

A

Bleeding after minor trauma

156
Q

What is thrombocytopenia?

A

a condition where we have a decrease in the platelet count

157
Q

A platelet count of <50,000/mm3 is as a result of ___

A

hemorrhage from minor trauma

158
Q

A platelet count of <15,000/mm3 is as a result of ___

A

spontaneous bleeding

159
Q

A platelet count of <10,000/mm3 is as a result of ___

A

severe bleeding

160
Q

What are the causes of thrombocytopenia?

A

• 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
Q

Thrombocytopenia manifests into…

A
  • 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
Q

What is petechiae?

A
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
Q

What is Purpura?

A
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
Q

An abnormal clot is called a ____

A

Thrombus

165
Q

A floating clot is called an ____

A

Embolus

166
Q

What are the 2 thromboembolic conditions?

A

Thrombus or embolus

167
Q

Thromboembolic conditions are caused by…?

A

• Endothelial roughening (e.g. atherosclerosis)
• Slow flow (e.g. prolonged air
travel)

168
Q

How are thromboembolic conditions treated?

A
  • tPA

* Embolectomy

169
Q

What is pulmonary embolism?

A

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
Q

Pulmonary embolism usually comes from ___. Treated by…

A

Deep leg veins.

Treated by tPA

171
Q

Disseminated intravascular coagulation occurs in ____

A

Occurs in the setting of massive tissue damage or sepsis

172
Q

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

A

Wide-spread coagulation in

small vessels

173
Q

Disseminated intravascular coagulation is manifested as….

A

Manifested as bleeding from
multiple sites because of
depletion of clotting factors

174
Q

Which blood coagulation test is used most often? And how is it done?

A

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
Q

What is the international normalized ration (INR) and why was it created?

A

Devised to standardize measurements of Prothrombin test and it was created because different testing procedures across different labs can produce different prothrombin times

176
Q

What are the 1st, 2nd, and 3rd line of defense in resistance to infection?

A
• 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
Q

What are the first line of defense and what do they do?

A
  • 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
Q

What is included in the Linings of the gastrointestinal, genitourinary, and respiratory tracts of the 1st line of defense?

A
  • Sloughing off of cells
  • Coughing and sneezing
  • Flushing—urine
  • Vomiting
  • Mucus and cilia
179
Q

The epithelial cell-derived chemical barriers secretion of saliva, tears, earwax, sweat and mucus does what?

A

It provides a barrier of protection

180
Q

The epithelial cell-derived chemical barriers antimicrobial peptides does what?

A

Kill bacteria upon contact.

181
Q

What are the antimicrobial peptides?

A

Cathelicidins, defensins, collectins, and mannose-binding lectin

182
Q

What does the normal microbiome do for the 1st line of defense?

A

Each surface colonized by bacteria and fungi that is unique to the particular location and individual provides helpful service

183
Q

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.

A

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
Q

What are the 5 cardinal signs of inflammation

A
  • Redness
  • Heat
  • Swelling
  • Pain
  • Loss of function
185
Q

What are the vascular responses of the inflammatory response in the 2nd line of defense?

A
  • 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
Q

What are the goals of inflammation?

A
  • Prevent and limit infection and further damage
  • Initiate adaptive immune response
  • Initiate healing
  • limit and control inflammatory process
187
Q

When are plasma protein systems activated?

A

Activated during inflammatory response to help WBCs and immune cells do their job

188
Q

What does plasma protein system: complement system do?

A

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
Q

What does plasma protein system: clotting system do?

A

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
Q

What does plasma protein system: Kinn system do?

A

Produces histamine like effects that increases permeability and stimulate nerve endings, producing pain

191
Q

What does “walling-off” sites of inflammation mean?

A

When fibronogen clots minimizes fluid flow in and out of the inflamed area. This controls inflammatory response and confines bacteria/prevents spreading

192
Q

____ causes intense inflammation and are effectively walled-off, as opposed to ___, which doesn’t and can lead to death

A

Staphylococci

Streptococci

193
Q

____ that encounter foreign particles enlarge and become mobile to provide a first line of defense, through phagocytosis

A

Tissue macrophages

194
Q

Within an hour neutrophils migrate to the area in response to ____, which is secreted by tissue macrophages and cells

A

inflammatory cytokines (TNF, IL-1)

195
Q

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

A

diapedesis, and chemotaxis

196
Q

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

A

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
Q

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 ____.

A

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
Q

Integrins are on ___ and selectins on ____. Neutrophil roll on endothelial surface from the interaction of ___ with ___

A

Integrins are on WBCs and selectins on endothelial cells. Neutrophil roll on endothelial surface from the interaction of integrins with selectins

199
Q

In response to ___ monocytes gradually accumulate

and become macrophages

A

Chemoattractants

200
Q

In part due to increased bone marrow production, __ become the dominant inflammatory cell

A

macrophages

201
Q

Growth factors produced in response to infection and inflammation drive proliferation
and differentiation of ___in the marrow

A

leukocyte precursors

202
Q

The bone marrow can increase production of ____by 20 – 50 fold and maintain this for months or years

A

neutrophils and monocytes

203
Q

What is pus composed of?

A

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
Q

Usually pus is absorbed by ___, but if the infection overwhelms this system, pus will accumulate and grow

A

The lymphatic system

205
Q

What two cell types release heparin, histamine, bradykinin and serotonin?

A

Basophils and mast cells

206
Q

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 ____

A

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
Q

What is the role of IgE in histamine release?

A

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
Q

What is the role of basophil and mast cells?

A

To initiate and maintain inflammatory response through attracting various cells and initiating and maintaining vascular response

209
Q

What is leukopenia and how does it happen?

A

Leukopenia, or low white blood cell count, is usually the result of reduced production of cells by the bone marrow

210
Q

What happens within two days of bone marrow shut down?

A

mucous membrane ulcers or

respiratory infection may occur

211
Q

What are the causes of leukopenia?

A

radiation, chemical toxins, some medicines or anything affecting bone marrow production

212
Q

What is leukemia?

A

Uncontrolled production of abnormal white blood cells due to a genetic mutation

213
Q

What are the cancer routes of leukemia?

A

Lymphocytic vs. myelogenous

214
Q

Types of leukemias get their names from…?

A

The type of cells that is affected

215
Q

What are the clinical effects of leukemia?

A

• 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
Q

How do cytotoxic T cells kill bacteria?

A

T-cells bind to invader cell and inserts bactericidial agents into it

217
Q

Helper T cells are __% of T cells and they regulate ___

A

75%, and they regulate functions of other immunologic cells by producing cytokines (IL-2-6, GM-CSF, and interferon-gamma)

218
Q

TH1 activates ___

A

Activates macrophages, cytotoxic T cells, and B cells

219
Q

TH2 activate __

A

Only B cells

220
Q

How do T-cells help the immune system?

A
  • 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
Q

Why are Helper T cells essential?

A

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
Q

T cells are encoded by ___

A

Major Histocompatibility Complex (MHC)

223
Q

MHC I present to ___

A

cytotoxic T cells (CD8)

224
Q

MHC II present to ____

A

helper T cells (CD4)

225
Q

Binding of antigen to MHC proteins increases the likelihood ___ will pick up the foreign protein fragment and activate

A

T-cell

226
Q

What are the two ways that T cells respond differently from B cells?

A
  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
Q

____ binds with antigen fragments and present them on cell surface

A

MHC protein

228
Q

The complement system is made up of 20 proteins that are made in the ___ and circulate the __ and ___

A

The complement system is made up of 20 proteins that are made in the liver and circulate the blood and ECF

229
Q

What are the 3 pathways in the complement system?

A
  • Classical pathway
  • Lectin pathway
  • Alternative pathway
230
Q

The early component of all 3 pathways in the complement system is to ___

A

Activate C3

231
Q

What is the function of C3?

A
  • 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
Q

People with ____ deficiency are subject to repeated bacterial infections

A

People with C3 deficiency

233
Q

Cleavage of each ___ activates the next component leading to an amplifying cascade in the complement system

A

Proenzyme

234
Q

What are the two things that many cleavages in the complement system liberate?

A
  1. Small active peptide fragments that can attract phagocytes
  2. Large membrane- binding fragments
235
Q

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 ___

A

Making the complement system confined to the particular cell surface where it began

236
Q

What are the classes of antibodies?

A
  • 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
Q

What is the mechanisms of action of antibodies?

A
  • Agglutination
  • Precipitation
  • Neutralization
  • Lysis
  • Complement activation
238
Q

What is agglutination?

A

When antibodies to antigen and clump together

239
Q

Where is precipication found?

A

Found in the blood and it also inactivates antibodies

240
Q

What is neutralization?

A

When antibodies bind to specific active sites on the pathogen or antigenic agent

241
Q

What is lysis?

A

The binding of antibodies initiates breakdown of pathogens

242
Q

Antibody production consist of…

A

• 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
Q

Antibody specificity is when each antibody has __

A

a steric configuration specific to its antigen

244
Q

Multiple prosthetic groups of each antigen interact with complementary structures of the antibody, through…

A
  • hydrophobic bonding
  • hydrogen bonding
  • ionic interactions
  • van der Waals forces
245
Q

Antibodies are at least ___

A

bivalent

246
Q

___ produces a greater and stronger immune response

A

Second exposure to anitgens

247
Q

Antibodies can inactivate ___ and ____ by binding to them

A

Inactivate viruses and microbial toxins by binding to them

248
Q

Once bound, antibodies can help recruit components of the ___

A

innate immune system

249
Q

Antibodies are exclusively synthesized by ___

A

B-cells

250
Q

___ are the most abundant proteins in the blood

A

Antibodies

251
Q

What is an autoimmune disorder?

A

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
Q

Examples of autoimmune disorders

A
  • 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
Q

What is the mechanism of immunological self-tolerance (that filter good lymphocytes from bad ones)?

A
  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
Q

If a defective lymphocyte passes from the central lymphoid organ, the body is unable to edit its receptor, instead the body will ___

A

Delete, inactivate, or suppress the entire colony.

255
Q

What suppresses a lymphocyte in the peripheral lymphoid organ?

A

Regulatory T-cell

256
Q

What do helper T cells activate?

A
  • Other killer T cells
  • B cells
  • Macrophages that secrete cytokines that promote lymphocyte growth and differentiation
257
Q

Both B and T cells require ____ to proliferate

A

Antigenic stimulation

258
Q

What do macrophages do for lymphocyte activation?

A
  • 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
Q

The acquired immune system works by ___

A

Clonal selection

260
Q

How does the clonal selection theory work?

A
  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
Q

Where does the T- lymphocyte differentiate/ develop?

A

In the thymus

262
Q

Hemopoietic stem cells can become __ progenitor cells or ____ progenitor cells

A

Common lymphoid progenitor cells or common myeloid progenitor cells

263
Q

B cells develop/ differentiate in the ___

A

Bone marrow

264
Q

___ mediate acquired immunity

A

Lymphocytes

265
Q

Lymphocytes are called ___ or ___ organs

A

Primary or central lymphoid organ

266
Q

Newly formed lymphocytes migrate from the ___ organs to the ___ organs

A

From the central organs to the peripheral organs

267
Q

What is an antigen?

A

A substance that can elicit an immune response

268
Q

The surface of each invading organism has a unique ___ that is made up of proteins or polysaccharides

A

Antigen

269
Q

What is an epitope?

A

The molecular structures that are specifically recognized in acquired immunity

270
Q

Once antigens are recognized by the immune system, the immune cells are ____

A

Activated and then can carry on with their effect

271
Q

What are antibodies?

A

activated cells that specifically target and destroy invading organisms and toxins

272
Q

What are the two types of acquired immunity?

A

Humoral (B cells)

Cell- mediated (T cells)

273
Q

The action of acquired immunity is performed through ___

A

Antibodies produced by B cells or Killer T cells that kill pathogens directly