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Fundamentals > Pathology - Erobbins > Flashcards

Pathology - Erobbins Flashcards

1
Q

What are the four principle adaptive responses of cells?

A

hypertrophy, hyperplasia, atrophy, and metaplasia

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2
Q

What characteristics of stress result in irreversible damage and cell death?

A

stress is severe, persistent and rapid in onset

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3
Q

What are physiologic adaptations?

A

represent responses of cells to normal stimulation by hormones or endogenous chemical mediators (e.g., the hormoneinduced enlargement of the breast and uterus during pregnancy)

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4
Q

What are pathologic adaptations?

A

responses to stress that allow cells to modulate their structure and function and thus escape injury

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5
Q

What are trophic triggers?

A

soluble mediators that stimulate cell growth such as growth factors and adrenergic hormones

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6
Q

Does metaplasia occur to mature cells?

A

No, metaplasia is thought to arise due to a change in gene expression in the stem cells

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7
Q

Compare and Contrast Apoptosis and Necrosis

A

Necrosis: Enlarged cell size, disrupted plasma membrane, enzymatic digestion, accompanies inflammation, always pathologic

Apoptosis: Reduced cell size, intact membrane, no inflammation, can be physiologic or pathologic

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8
Q

Differentiate hypoxia from ischemia

A

Ischemia is the inadequate supply of oxygen to a tissue due to a physical obstruction, hypoxia is inadequate supply of oxygen because of a lowered concentration of oxygen in the blood

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9
Q

What are the common causes of cell injury?

A

Oxygen Deprivation, Chemical Agents, Infectious Agents, Immunologic Reactions, Genetic factors, Nutritional Imbalances, Physical agents, and Aging

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10
Q

Can we immediately see cell death?

A

No, cell death occurs before any accompanying ultrastructural changes that can be seen by light microscopy and even longer before any gross morphological changes

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11
Q

Which two characteristics are consistent signs that cell damage has become irreversible?

A

The inability to correct mitochondrial dysfunction and profound disturbances in membrane function

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12
Q

What are the major morpholigical correlates of reversible cell injury?

A

Cellular swellin due to failure of energy dependent ion pumps and Fatty change resulting in the appearance of lipid vacuoles in the cytoplasm. Dilation of the ER with detachment of ribosomes, and nuclear alterations with clumping of chromatin

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13
Q

What type of necrosis is characteristic of infarcts?

A

Coagulative necrosis (everywhere but the CNS)

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14
Q

What are the four principal targets and biomechanical mechanisms of cell injury?

A
  1. Mitochondria and their ability to generate ATP and ROS
  2. Disturbance of Ca2+ homeostasis
  3. Damage to cellular membranes
  4. Damage to DNA and protein misfolding
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15
Q

What are the effects of Mitochondrial damage?

A

Decrease in ATP production leading to multiple downstream effects and an increase in ROS leading to lipid, protein, and DNA damage

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16
Q

What are the effects of increased Ca2+ permeability?

A

Entry of calcium leads to increased mitochondrial permeability and activation of multiple cellular enzymes

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17
Q

What are the effect of membrane damage?

A

Plasma membrane damage leads to the loss of cellular components, lysosomal membrane damage leads to the digestion of cellular components

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18
Q

What are the effects of protein misfolding and DNA damage?

A

Activation of pro-apoptotic proteins leading to eventual apoptosis

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19
Q

What are the effects of mitochondrial damage?

A
  1. Increased influx of Ca2+, H20, and Na+ leading to cellular swelling and loss of microvilli
  2. Increased efflux of K+
  3. Decreased ATP production
  4. Increased glycolysis leading to increased lactic acid production and decreased pH
  5. Detachment of ribosomes leading to decrease production of proteins
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20
Q

What changes cause mitochondria to undergo necrotic changes? Apoptotic Changes?

A
  • Necrosis: Decreased O2 supply, Toxins, Radiation lead to decreased ATP and increase in reactive oxygen species
  • Apoptosis: Decreased survival signals, DNA or Protien damage results in leakage of mitochondrial proteins and apoptosis
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21
Q

How do cells get rid of free radicals?

A
  1. The rate of decay of superoxide is increased by Superoxide Dismutases
  2. Glutathione peroxidase in teh cytoplasm of cells catalyzes the breakdown of H2O2 into H2O
    1. GS-SG + H2O2 = 2GSH + 2H20
  3. Catalase is peroxisomes breaks down H2O2 extremely quickly
  4. Endogenous antioxidants prevent formation of free radicals or quickly bind them
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22
Q

How do ROS cause cell injury?

A
  • Lipid peroxidation of membranes resulting in an autocatalytic radical chain
  • Promotion of sulfhydryl protein cross-linking leading to enhanced degredation or loss of activity
  • DNA damage via reaction with thymine in nuclear and mitochondrial DNA
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23
Q

What are the mechanisms of membrane damage in cell injury?

A
  • Decreased phospholipid synthesis due to decrease in concentration of ATP
  • Increased phospholipid breakdown by endogenous phospholipases activated by increased cytosolic Ca2+ levels
  • Lipid peroxidation by free radicals
  • Activation of proteases leading to cytoskeletal damage and eventually membrane damage
  • Presence of lipid breakdown products act as a detergent to cell membranes
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24
Q

Describe the mitochondrial pathway of apoptosis

A

Cell injury leads to Bcl-2 family sensors activating Bax and Bak which cause increased mitochondrial permeability allowing cytochrome C to enter the cytosol and activate caspases that cleave proteins at aspartic residues leading to nuclear degredation and membrane blebbing and eventual apoptosis

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25
Q

Describe the death receptor pathway of apoptosis

A

Fas or TNF receptors are activated by ligand, they in turn activate adapter proteins which activate caspases resulting in nuclear fragmentation and membrane blebbing leading to eventual apoptosis

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26
Q

How do Bax and Bak increase mitochondrial membrane permeability?

A

They dimerize and enter the mitochondrial membrane to form channels through which cytochrome C and other pro-apoptotic proteins can travel

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27
Q

What are the five external manifestations of inflammation and their latin names?

A
  1. Heat (Calor)
  2. Redness (Rubor)
  3. Swelling (Tumor)
  4. Pain (Dolor)
  5. Loss of function (functio laesa)
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28
Q

What vascular change occurs during inflammation?

A

Vasodilation and increased vascular permeability, additionally endothelial cells are activated leading to increased adhesion to leukocytes

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29
Q

What cellular events occur during inflammation?

A

Emigration of leukocytes from the circulation (Margination, Rolling, Adhesion, Diapedesis) as well as activation of leukoctyes allowing them to remove the offending agent

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30
Q

What stimuli can trigger acute inflammation?

A

Infections, Trauma, Tissue necrosis, foreign bodies, and immune reactions.

All have characteristics that are distinctive but share the same basic features.

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31
Q

What are the two most important families of Pattern Recognition Receptors?

A

Toll-like receptors and the Inflammasome

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32
Q

What are toll-like receptors (TLRs)?

A

Microbial sensors present on the cell membrane and in the endosomes so they can recognize both internal and external pathogens.

They recognize products from different types of microbes and are able to provide defense against all classes of infectious pathogens.

Activate transcription factors for a number of secreted and membrane proteins

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33
Q

What is “The Inflammasome”?

A

A multiprotein cytoplasmic complex that recognizes the products of cellular death.

Triggering the inflammasome activates caspase 1 which activates IL-1B which is an important mediator of leukocyte recruitment.

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34
Q

Describe how vasodilation leads to margination

A

Following transient vasoconstriction the smooth muscle walls of the blood vessels relax allowing more blood flow. Additionally exudate flows from the blood vessel into the tissues increasing the concentration of RBCs which increases viscosity and slows blood flow. The slowed blood flow results in leukocytes moving toward the vessels walls and “rolling” due to interaction with selectins.

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35
Q

What factors account for rapid and prolonged endothelial cell contraction?

A
  • Rapid: Histamines, bradykinins, leukotrienes, and specific mediators
  • Prolonged: Changes in the cytoskeleton caused by cytokines like TNF and IL-1
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36
Q

What cytokines influence the expression of P and E selectin and the ligand for L selectin on the surface of endothelial cells?

A

IL-1 and TNF secreted by macrophages which have phagocytized infecting microbes

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37
Q

Following activation of leukocytes by chemokines, which integrins are expressed and what do they bind which allows for adhesion to the endothelium.

A

LFA-1 and VLA-4 are expressed in their high affinity form on leukocytes. These bind to ICAM-1 and VCAM-1 respectively which are expressed on endothelial cells after activation by IL-1 and TNF

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38
Q

What cellular adhesion molecule is responsible for diapedesis?

A

CD31 also called PECAM-1 (Platelet endothelial cell adhesion molecule 1)

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39
Q

What exogenous and endogenous substances are chemotaxic for leukocytes following diapedesis?

A

Bacterial products, chemokines, complement C5a, and LTB4 (a product of the lipoxygenase pathway of arachidonic acid metabolism)

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40
Q

What factors account for the early abundance of neutrophils during the first 6-24 hours of infection?

A
  • Neutrophils are the most numerous leukocyte in the blood
  • They respond more rapidly to chemokines and may attach more firmly to adhesion molecules expressed on activated endothelial cells
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41
Q

Which functions of leukocytes are enhanced by activation?

A
  1. Phagocytosis of particles
  2. Intracellular destruction of phagoctosed microbes and dead cells
  3. Liberation of substances that destroy extracellular microbes and dead tissues
  4. Production of mediators including arachadonic acid metabolits and cytokines which produce a positive feedback recruitment of leukocytes
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42
Q

What receptors present on Leukocytes recognize opsonins resulting in increased phagocytosis?

A
  • FcyRi recognizes IgGs
  • CR1 and CR3 recognize complement fragments
  • C1q recognizes the collectins
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43
Q

What are the three steps of phagocytosis?

A
  1. Attachment and binding
  2. Englufment and fusion of phagosome with lysosomes to form phagolysosome
  3. Destruction of ingested particles by iNOS, NO, and ROS
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44
Q

What are the lysosomes of neutrophils called?

A

Azurophilic granules

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45
Q

Following oxidative burst what occurs to breadown and kill bacteria in the phagolysosome?

A

Superoxides are created which spontaneously dismute to form H2O2. Myeloperosidase (MPO) in the presence of a halide converts H2O2 into hypochlourous radical (bleach) which kills bacteria by halogenation or by protein and lipid peroxidation.

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46
Q

Which other constituents of leukocytes granuoles are capable of killing pathogens?

A
  1. Bactericidal permeability-increasing protein
  2. lysozyme
  3. major basic protein
  4. defensins
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47
Q

How are the contents of microbicidal granules secreted into the extracellular space?

A
  • The phagocytic granule may remain transiently open before complete closure of the phagolysosome
  • Attempts to phagocytise materials that are not easily ingested triggers release of lysosomal enzymes
  • The membrane of the phagolysosome may be partially damaged leading to the expulsion of its contents
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48
Q

Which cells in the tissue produce cell derived mediators?

A

Tissue macrophages, mast cells, and endothelial cells at the site of inflammation

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49
Q

What two vasoactive amines are among the first mediators to be released in acute inflammatory reactions and how are they stored?

A

Histamine and Serotonin are stored in preformed secretory granules

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50
Q

What stimuli cause the release of histamine from mast cell granules?

A
  • Physical injury
  • Immune reactions involving binding of IgE to Fc receptors on mast cells
  • C3a and C5a fragments (anaphylatoxins)
  • Leukocyte derived histamine releasing proteins
  • Neuropeptides (substance P)
  • Certain cytokines (IL-1, IL-8)
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51
Q

How does Serotonin function when released?

A

Serotonin functions in vasoconstriction. It is stored in secretory granules of platelets and is released during platelet aggregation. It is produced mainly in neurons and entereochromaffin cells.

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52
Q

What is the collective name for the metabolites of Arachidonic Acid

A

Eicosanoids

53
Q

What cell types are the major source of eicosanoids that mediate inflammation?

A

Leukocytes, mast cells, endothelial cells, and platelets

54
Q

Which eicosanoids act in vasodilation?

A

Prostaglandins PGI2, PGE1, PGE2, PGD2

55
Q

What eicosanoids act in vasoconstriction?

A

Thromboxane A2, Leukotrienes C4, D4, E4

56
Q

What eiconsanoids increase vascular permeability?

A

Leukotrienes C4, D4, E4

57
Q

What eicosanoids act as chemotactic signals and in leukocyte adhesion?

A

Leukotriene B4, HETE

58
Q

What are the two major pathways of AA metabolism and what are the products of each?

A
  1. Cyclooxygenase pathway: prostaglandins and thromboxanes
  2. Lipoxygenase pathway: leukotrienes and lipoxins
59
Q

What drug classes inhibit the action of phospholipases and prevent the production of arachadonic acid?

A

Steroids

60
Q

What drug classes inhibit the cyclooxygenase pathway and prevent the synthesis of prostaglandins and thromboxanes?

A
  • COX1 and COX2 inhibitors
  • Aspirin
  • Indomethacin
61
Q

What protaglandin inhibits platelet aggregation and what eicosanoid works against it to promote platelet aggregation?

A

PGI2 inhibits platelet aggregation and causes vasodilation

TXA2 promotes platelet aggregation and causes vasoconstriction

62
Q

What is the major AA metabolizing enzyme in neutrophils and what does it produce?

A

5-lipoxygenase produces leukotrienes

(LTA4 gives rise to LTB4 or LTC4. LTC4 is subsequently broken down into LTD4 and LTE4)

LTB4 is a potent chemotactic agent for neutrophils

LTC4, D4, E4 are produced primarily in mast cells and promote bronchoconstriction and vasodilation

63
Q

What metabolic changes happen once leukocytes enter tissues?

A

They change their major lipoxygenase derive AA products from Leukotrienes to Lipoxins. Lipoxins are anti-inflammatory mediators that inhibit neutrophil chemotaxis and adhesion to the endothelium.

64
Q

Why are COX-2 inhibitors potentially better anti-inflammatory drugs than COX-1 inhibitors, what are some of their drawbacks and why?

A

COX-2 is expressed only in response to inflammatory signals and in contrast to COX-1 is not expressed in normal tissues. Therefore inhibiting COX-2 blocks inflammation without disruption of normal COX activity in tissue.

COX-2 inhibitors are associated with clotting issues because TXA2 is still produced via the COX-1 pathway but PGI2 production is blocked resulting in increased risk of pathologic platelet aggregation

65
Q

What is platelet activating factor? Why is it important? In what cell types is it produced?

A

PAF is a phospholipid derived mediator with a number of inflammatory effects. It acts on target cells through specific GPCRs to stimulate production of eicosanoids and cytokines from platelets and other cells. It is produced by PLA2 activity on membranes of neutrophils, monocytes, basophils, endothelial cells, and platelets. It is 100-1000x more potent for vasodilation and vascular permeability than histamine

66
Q

What are the major cytokines of acute inflammation?

A

TNF, IL-1, IL-6, and Chemokines

67
Q

What are the major cytokines of chronic inflammation?

A

IFNy and IL-12

68
Q

Where are TNF and IL-1 produced? What is their major role in inflammation?

A

TNF and IL-1 are produced in macrophages, mast cells, endothelial cells, and some other cells types in response to bacteria, immune response, and T lymphocyte products. IL-1 and TNF function to increase the expression of integrins on the endothelial cell surface and allow for adhesion and diapedesis of leukocytes.

69
Q

What is the characteristic difference between CC and CXC chemokines? On which cells do CXC chemokines act?

A

CC chemokines have two consecutive cysteine residues, CXC chemokines have one amino acid in between two cysteine residues.

CXC chemokines act primarily on neutrophils (IL-8 is an example of this group)

70
Q

What acts at low levels to increase chemokine, cytokine, and adhesion molecule expression?

A

Reactive Oxygen Species (ROS)

71
Q

What happens when ROS have too high of concentrations in the tissue?

A
  • Endothelial damage with thrombosis and increased permeability
  • Protease activation and antiprotease inactivation
  • Direct injury to other cell types
72
Q

What types of NO play important roles in inflammation? What are their specific roles? What else does NO do?

A

Type II NO (iNOS) and Type III NO (eNOS) both have active roles as microbicidal agents in activated macrophoges. Type II is synthesized in macrophages in response to IL-1, TNF, and IFNy. Type III is constitutively expressed in endothelial cells. NO also acts as a vasodilator, an inhibitor of platelet activations, and a reducer of leukocyte recruitment.

73
Q

In what complement pathway is C1 important?

A

The classical complement pathway

74
Q

What are the effects of the C5a subunit circulating in the blood?

A

Acts to promote the release of histamine, to recruit leukocytes, and to promote the lypoxegenase pathway in neutrophils stimulating the release of additional proinflammatory AA derivatives (leukotrienes)

75
Q

What four systems that contribute to the inflammatory response are activated by Hegeman factor (Factor XII)?

A
  1. The kinin system producing vasoactive kinins
  2. The clotting system inducing the activation of thrombin, fibrinopeptides, and factor X
  3. The fibrinolytic system producing plasmin and inactivating thrombin
  4. The complement system producing C3a and C5a (anaphylotoxins)
76
Q

What is the function of the kinin system?

A

The kinin system produces bradykinin from it’s precursor high molecular weight kinin (HMWK). Bradykinin is active in vascular permeability, arterioloar dilation and bronchial smooth muscle contraction.

One of the steps in the cascade is killikrein which is a potent activator of Factor XII

77
Q

How is the clotting system linked to inflammation and the complement cascade?

A

The production of thrombin which cleave fibrinogen to fibrin has an intermediate in the cascade called Factor Xa which acts to promote vascular permeability and leukocyte emigration.

Thrombin also cleaves C5 to generate C5a, a potent vasodilator and chemotaxic signal for neutrophils

Thrombin also binds to endothelial cells to increase cellular adhesion

78
Q

What are the major mediators responsible for vasodilation?

A

Prostaglandins, nitric oxide, and histamine

79
Q

What are the major mediators of increased vascular permeability?

A

Histamine and seratonin

C3a and C5a (via mast cell histamine release)

Bradykinin

Leukotrienes C4, D4, E4

PAF

Substance P

80
Q

What are the major mediators responsible for chemotaxis, leukocyte recruitment and activation?

A

TNF, IL-1

Chemokines (IL-8)

C3a and C5a

Leukotriene B4

Bacterial products (N-formyl methyl peptides)

81
Q

What are the major mediators responsible for fever?

A

IL-1, TNF

Prostaglandins

82
Q

What are the major mediators responsible for pain?

A

Prostaglandins and Bradykinins

83
Q

What are the major mediators responsible for tissue damage?

A

Lysosomal enzymes of leukocytes

ROS

NO

84
Q

What are some of the major anti-inflammatory mediators?

A

Lypoxins

Complement regulatory proteins (Factor H, DAF, etc)

IL-10 (negative feedback from activated macrophages)

TGF-b (also mediate fibrosis in tissue repair following inflammation)

Intracellular proteins like tyrosine phophotases

85
Q

What are the hallmarks of chronic inflammation?

A
  • Infiltration with mononuclear cells (macrophages, lymphocytes, plasma cells)
  • Tissue destruction (Largely from inflammatory cell products)
  • Repair involving angiogenesis and fibrosis
86
Q

From what settings do chronic inflammation typically arise?

A
  • Persistent infections (difficult to eradicate microbes)
  • Immune mediated inflammatory diseases
  • Prolonged exposure to potentially toxic agents
87
Q

Describe the role of classical activation of macrophages? What cytokines are involved and what is the primary role of activated macrophages?

A

Classical activation of macrophages occurs due to bacterial endotoxin and the secretion of IFN-y from T-cells. Activation increases production of lysosomal enzymes, NO, and ROS resulting in increased microbicidal activity.

88
Q

Describe alternative activation of macrophages. What cytokines are involved and what is the primary function of active macrophages?

A

Cytokines such as IL-4 and IL-13 secreted by T-cells, mast cells and eosinophils activate the macrophage to produce growth factors that promote angiogenesis, activate fibroblasts, and stimulate collagen synthesis. These macrophages are primarily active in tissue repair.

89
Q

What are the critical roles of macrophages in host defense?

A
  • Ingest and eliminate microbes and dead tissues
  • Initiate the process of tissue repair
  • Secrete mediators of inflammation
  • Display antigen to T lymphocytes and respond to signals from T cells
  • (IFN-y can also cause macrophages to fuse into giant cells)
90
Q

What is the function of activate CD4+ T cells in the tissue?

A

CD4+ T cells secrete cytokines

(Th1 cells secrete IFN-y, Th2 cells secrete IL-4, IL-5 and IL-13, Th17 cells secrete IL-17 and other cytokines responsible for recruitment of neutrophils and monocytes)

91
Q

What types of CD4+ cells are responsible for defense against helminthic parasites and in allergic inflammation?

A

Th2 cells (secrete IL-4, IL-5, and IL-13)

92
Q

What types of CD4+ cells are responsible for defense against bacteria and viruses and against autoimmune disease?

A

Th1 and Th17 cells

93
Q

Which cytokines are the most important mediators of the systemic acute phase reaction?

A

IL-1, IL-6, TNF

94
Q

What are the clinical findings associated with the actue phase reaction?

A

Fever, elevated plasma levels of acute phase proteins, and leukocytosis.

(Additionally increased heart rate and blood pressure, decreased sweating, shivering, chills, anorexia, somnolence, and malaise)

95
Q

How does fever come about in the acute phase reaction?

A

Pyrogens such as LPS stimulate leukocytes to release cytokines IL-1 and TNF which increase levels of COX activity and stimulate the production of prostaglandins. Prostaglandins interact with the hypothalamus (Especially PGE2) to stimulate neurotransmitter release which is responsible for raising the body’s set temperature point.

(NSAIDs block COX activity and therefore help to reduce fever)

96
Q

How do elevated levels of acute-phase proteins in the blood come about? Which proteins are specifically important?

A

IL-6 stimulates the release of the acute phase proteins C-reactive protein, fibrinogen, and serum amyloid A (CRP, Fibrinogen, and SAA).

Fibrinogen binds to RBCs and causes formation of rouleaux which sediment faster (reason for doing ESR)

CRP and SAA bind to microbes and act as opsonizing agents assisting in their elimination

97
Q

What kind of shift in cell type is characteristic of leukocytosis?

A

A “left-shift” toward a more immature cell type is noticed due to increased demand for leukocytes.

Levels are typically elevated to 15000-20000

A leukemoid reaction occurs when levels are greater than 25000

98
Q

What is regeneration? What kind of injury causes it to occur?

A

The replacement of damage cells in tissue with the same type of cells and return to a normal state. This occurs when only the epithelial layer is damage, once the stem cells are damaged then scar formation must occur.

99
Q

What is an organ that is notable for it’s regeneration?

A

The liver

100
Q

When does scar formation occur?

A

Scar formation occurs when injured tissues lack the ability to regenerate, or if the tissue’s supporting structures like the basement membrane are severely damaged. Tissue that has a scar cannot perform the same function but the scar does add the necessary stability.

101
Q

What two rates control the number of cells that are present in a given tissue?

A

The rate of cell proliferation and the rate of apoptosis

102
Q

What are labile tissues? Give examples of where they might be found.

A

Labile tissues are continuously dividing to replace cells that are continuously being lost. Labile cells include hematopoietic cells in the bone marrow and the majority of surface epithelia.

These tissues can readily regenerate after injury as long as the pool of stem cells is preserved

103
Q

What are stable tissues? Give examples of where they would be found.

A

Cells in stable tissues are quiescent and only replicate a little when they are in their normal state however when stimulated by growth factors they replicate readily in response to injury or loss of mass. They constitute the parenchyma of most organs such as the liver, kidneys, and pancreas.

104
Q

What are permanent tissues and where are they found?

A

Permanent tissues lack the ability to proliferate and they are terminally differentiated. They include the myocardial cells, skeletal muscle, and nervous tissue. Any damage to permanent tissues is repaired by scar formation.

105
Q

What are the two characteristic properties of stem cells?

A

Assymetric cell division and self renewal

106
Q

What are the functions of growth factors?

A
  • They induce cell proliferation by binding to receptors
  • Promote entry of cells into the cell cycle
  • Remove blocks to cell cycle progression
  • Prevent apoptosis
  • Enhance the synthesis of cellular proteins in preparation for mitosis
107
Q

Where is Vascular Endothelial Growth Factors produced and what are their functions?

A

VEGF is produced by mesenchymal cells, it stimulates proliferation of endothelial cells and increases vascular permeability

108
Q

What is Platelet Derived Growth Factor and what does it do?

A

PDGF is produced by platelets, macrophages, endothelial cells, smooth muscle cells and keratinocytes. It is chemotactic for neutrophils, macrophages, fibroblasts, and smooth muscle cells. It activates and stimulates proliferation of fibroblasts, endothelial cells and stimulates ECM protein synthesis

109
Q

Where is Fibroblast Growth Factor produced and what are it’s functions?

A

FGF is produced by macrophages, mast cells, endothelial cells, and many other cell types

It is chemotactic and mitogenic for fibroblasts; it stimulates angiogenesis and ECM protein synthesis.

110
Q

What is Hemostasis

A

the process of blood clotting that prevents excessive bleeding after blood vessel damage

111
Q

What is the difference between hyperemia and congestion?

A

Hyperemia is a condition caused by excess inflow of blood to the effected tissue. Congestion is caused by not enough venous draining.

112
Q

What are the major pathophysiologic causes of edema and what are some of the conditions that they are responsible for?

A
  • Impaired venous return (congestive heart failure, constrictive pericarditis, ascites)
  • Venous obstruction or compression (Thrombosis, externam pressure, DVT)
  • Arteriolar Dilation (Heat, neurohumoral dysregulation)
  • Reduced plasma osmotic pressure (glomerulonephropathies, cirrosis, malnutrition, gastroenteropathy)
  • Lymphatic Obstruction
  • Sodium Retention, Inflammation
    *
113
Q

What are the two opposing forces that guide fluid movement between the cascular and interstitial spaces?

A

vascular hydrostatic pressure and the colloid osmotic pressure

114
Q

Where is vascular pressure greater? Where is colloid pressure greater?

A

Vascular pressure is slightly greater at the arteriolar side of the capillary bed. Colloid pressure is slightly greater at the venous side of the capillary bed.

Small outflow into the interstitial space is drained by the lymphatic system.

115
Q

What is the difference between fluid accumulating in the tissue due to a change in the ratio of hydrostatic pressure and colloid pressure and a fluid that accumulates due to inflammatory edema?

A

Fluid accumulating as a result of changes in pressure is typically a protein-poor transudae with a specific gravity lower than 1.012. Fluid that accumulates due to inflammation is typically protein rich because of the increased vascular permeability and is called exudate with a specific gravity of 1.020 or greater.

116
Q

Under normal circumstances what accounts for almost half of the circulating plasma proteins?

A

Albumin, therefor conditions where albumin is lost typically is a common cause of reduced plasma osmotic pressure leading to tissue edema, reduced intravascular volume, renal hypoperfusion, and secondary hyperaldosteronism.

117
Q

What is commoly caused by lymphatic obstruction?

A

Lymphatic obstruction leads to a decrease in drainage of excess fluid form the tissues. Excess fluid is no longer adequately drained it can cause edema.

118
Q

What are petechiae?

A

Minute hemorrhages into skin, mucous membranes, or serosal surfaces. Causes include low platelet counts, defective platelet function, and loss of vascular wall support as seen in vitamin C deficiency.

119
Q

What are pupura?

A

Slightly larger (3-5mm) hemorrhages that can result from the same disorders that cause petechiae as well trauma, vascular inflammation, and increased vascular fragility.

120
Q

What are ecchymoses?

A

Ecchymoses are larger (1-2cm) subcutaneous hematomas. Characteristic colors of a bruise are due to the enzymatic conversion of hemoglobin (red-blue) to bilirubin (blue-green) and eventually hemosiderin (golden brown).

121
Q

How much blood must over a short period of time to result in hypovolemic shock?

A

>20% of the blood volume

122
Q

What can frequent external hemorrhage lead to that internal hemorrhage to form hematomas cannot?

A

Anemia (Iron deficiency)

123
Q

What is the general mechanism of hemostasis?

A
  1. Vascular injury results in neurogenic vasoconstriction augmented by endothelin secreted by the endothelial cells.
  2. Exposed ECM produces thrombin which activated platelet adherence and aggregation.
  3. Tissue factor in conjuction with factor 7 triggers the coagulation cascade and activated thrombin
  4. Thrombin cleaves fibrinogen to fibrin promoting clot formation.
124
Q

What three primary abnormalities lead to thrombosis? (Virchow’s Triad)

A

Endothelial Injury, Abnormal Blood Flow, Hypercoagulability

125
Q

What genetic mutations lead to hypercoagulability?

A
  • Factor V mutation
  • Prothrombin mutation
  • 5,10 methylene tetrahydrofolate reductase
  • Increased levels of factor VIII, IX, or XI or fibrinogen (Intrinsic pathway)(Decreased PTT)
  • More rare are (Antithrombin III deficiency and Protein C and S deficiency)
  • Very rare are fibrinolysis defects and homozygous homocystinuria
126
Q

What acquired characteristics lead to higher risk for thrombosis?

A
  • Immobilization
  • Myocardial infarction
  • Atrial fibrillation (turbulent flow)
  • Tissue injury
  • Cancer
  • Prosthetic cardiac valves
  • DIC
  • Heparin induced thrombocytopenia
  • antiphospholipid antibody syndrome
127
Q

What are the four potential fates of thrombi?

A
  • Propagation (it gets bigger)
  • Embolization (it dislodges)
  • Dissolution (it breaks down, harder over time)
  • Organization and recanalization (it dissolves in the middle allowing blood flow, or new vessels grow around it restoring blood flow)
128
Q

What are the characteristics of a Fat Embolism

A
  • 1-3 days after severe bone trauma
  • tachypnea
  • dypnea
  • tachycardia
  • irritibility
  • restlessness progressing to delirium or coma
129
Q
A

Fundamentals (12 decks)

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