Lecture 3.1 Flashcards
1
Q
Essential Components of Animal Cells; describe the purposes of:
1) Nucleus
2) Ribosomes
3) Mitochondria (name 2 specific aspects)
A
1) DNA storage, transcription and synthesis, mRNA processing
2) Translation
3) Energy production; apoptosis
-Oxidative phosphorylation
-Cytochrome C
2
Q
Essential Components of Animal Cells; describe the purposes of:
1) ER (for each of the two parts)
2) Golgi
3) Lysosomes
A
1) -Rough and smooth: Rough folds and processes proteins
-Smooth produces lipids
2) Modifies proteins for transportation
3) Digestive enzymes for macromolecules: Protein, polysaccharides, lipids, nucleic acids
3
Q
Essential Components of Animal Cells; describe the purposes of:
1) Proteosomes
2) Peroxisomes
3) Cytoskeleton
4) Plasma membrane
A
1) Degrade proteins
2) Oxidative enzymes for long chain fatty acid metabolism
3) Cell shape, polarity (orientation), organization and movement of organelles, cell motility
4) Regulated movement of solutes, cell-to-cell interaction
4
Q
What are the 3 ways lysosomes/ proteasomes are formed?
A
1) Through pinocytosis or receptor mediated endocytosis
2) Phagocytosis – microorganisms are engulfed to form phagosome
3) Autophagy – large proteins and organelles are surrounded by ER membrane and “fed” to the lysosome
5
Q
What is the job of proteasomes?
A
Denatured or misfolded proteins are tagged with “ubiquitin” then disassembled here
6
Q
How many different hydrolases are there to tear stuff apart?
A
40
7
Q
1) What’s permeable to the plasma membrane?
2) What’s impermeable?
A
1) Very small particles, non-polar particles
-Water, O2, CO2, ethanol, steroids, vit D
2) Polar particles, large particles
-Proteins, glucose, ions
8
Q
List the 4 primary ways to get through the plasma membrane
A
1) Passive transport
2) Active
3) Endocytosis
4) Phagocytosis
9
Q
1) Passive transport: which method is fast and which is slow?
2) What mediates this?
A
1) Channels (fast), carriers (slow)
2) Receptors
10
Q
What are the two types of endocytosis?
A
1) Caveolae mediated - “little cave”
2) Receptor mediated – clathrin; LDL and transferrin
11
Q
What is responsible for the synthesis of transmembrane proteins and lipids?
A
ER/ golgi
12
Q
Rough ER:
1) _______________ molecules ensure protein is properly folded.
2) Excess accumulation of misfolded proteins leads to what? What does this cause?
A
1) Chaperone
2) Unfolded protein response; apoptosis
13
Q
Smooth ER:
1) What does it synthesize?
2) What does it catabolize?
3) What does it store?
A
1) Steroids (gonads and adrenals)
2) Lipid-soluble molecules (liver)
2) Calcium (muscle “sarcoplasmic reticulum”)
14
Q
Golgi apparatus:
1) What does it do?
2) What added to proteins in the ER are modified here?
A
1) Packaging to organelles or plasma membrane
2) N-linked oligosaccharide
15
Q
Mitochondria’s cytochrome C is involved in what?
A
Apoptosis
16
Q
What are the 2 types of receptors?
A
Extracellular + intracellular
17
Q
1) Thing that “lands” on a receptor is called what?
2) What are the two things this thing can do?
A
1) A ligand
2) -Either initiate a second messenger system to start intracellular functions
Or
-It can interact directly with DNA and affect transcription
18
Q
List 4 types of receptors
A
1) Receptor tyrosine kinases (RTKs)
2) Kinase activity
3) G-protein coupled receptors
4) Steroids
19
Q
1) True or false: DNA-binding domains permit specific binding to short DNA sequences
2) Sometimes transcription factors bind in what region?
A
1) True
2) Promoter
20
Q
1) Sometimes transcription factors bind to what long-range regulatory elements? What do these do?
2) What are elements?
A
1)”Enhancers”; though far away, “loop back” to interact with the genes they regulate
2) Pieces of DNA
21
Q
Growth Factors:
1) What do they do?
2) How do they do this?
3) What do they prevent?
A
1) Promote entry of cells into the cell cycle; promote replication
2) Enhance biosynthesis of cellular components
Nucleic acids, proteins, lipids, carbohydrates
Done to provide the machinery necessary to create daughter cells
3) Apoptosis
22
Q
List 2 growth factors involved in regeneration and repair
A
1) Epidermal growth factor (EGF)
2) Vascular endothelial growth factor (VEGF)
23
Q
1) What do totipotent stem cells do?
2) What can adult stem cells do?
A
1) Give rise to all types of differentiated tissues
2) Only have capacity to replace damaged cells of the same type
24
Q
1) What type of medicine uses stem cells to heal patients?
2) Why is this difficult?
A
1) Regenerative medicine
2) Difficulty lies in implanting cells in patients that remain located at site of damage
25
Causes of cell injury; explain the mechanisms of:
1) Hypoxia/Ischemia
2) Infection
1) Cell function disrupted > damage cell
2) TB/fungus, bacteria, everything else > damage cell
Inflammatory response and leukocytes > damage cell
26
Causes of cell injury; explain:
1) Autoimmune disease
2) Toxins
3) Then list some other misc causes
1) Your own body damage cells
2) Toxins damage cell
3) Immunologic reaction, physical agents, genetic abnormality, nutritional imbalance, aging
27
List and define each type of toxin
1) **Direct-acting:** combine with critical molecular component or cellular organelle, disrupting its function i.e. mercury
2) **Latent toxins:** these are converted from benign to reactive metabolites which act on target cells
3) **Reactive Oxygen Species (ROS):** free radicals that are highly reactive and react with cellular components, destroying them
28
Mercury is an example of what kind of toxin?
Direct-acting
29
1) What kind of toxins are converted from benign to reactive metabolites which act on target cells?
2) What are free radicals that are highly reactive and react with cellular components, destroying them, called?
1) Latent toxins
2) Reactive oxygen species (ROS)
30
Give 2 examples of ROS
Hydrogen peroxide, radiation
31
What may happen during a reversible cell injury? (4 things)
1) Intracellular swelling
2) Mitochondria and ER
3) Plasma membrane blebbing (think tiny little ball)
4) Clumping of chromatin in nucleus
5) Myelin figures (actually phospholipids that are bits of damaged plasma membrane)
32
What are Myelin figures?
Actually phospholipids that are bits of damaged plasma membrane
33
List 3 signs of irreversible cell damage
1) Inability to restore mitochondrial function
2) Loss of structure and function of plasma membrane
3) Loss of DNA and chromatin structural integrity
34
What are 3 features of *controlled* cell death?
1) Organized disassembly
2) Membrane bound > no inflammation
3) One cell or a small group
35
1) Define apoptosis
2) When does it happen in development?
3) When else does it occur?
1) Controlled or programmed cell death
2) Embriogenesis
3) Irreversible injury that is recognized in time to control cell demise
36
1) Define necrosis?
2) What does it cause?
3) Is it usually one cell, or more? Explain
1) Unprogrammed, violent death
2) Swelling > eventual lysis of the cell > inflammation
3) Usually wide-spread; many cells or entire organ
37
List 4 types of adaptation to cellular injury
1) Hypertrophy
2) Hyperplasia
3) Atrophy
4) Metaplasia
38
Out of the 4 forms of adaptation:
1) Which reference cell size?
2) Which references cell number?
3) Which refers to cell type?
1) Hypertrophy and atrophy
2) Hyperplasia
3) Metaplasia
39
Hypertrophy:
1) Can all cells do this? Give an example of when this occurs
2) Can it be pathologic?
1) Available to all types of cells – in the case of muscle, response to increased demands
2) Yes, can become pathologic, as in the case of heart muscle
40
Give 2 physiologic examples of hyperplasia
1) The proliferation of glandular epithelium of female breast at puberty and pregnancy
2) When residual tissue returns after part of an organ is lost
41
When can hyperplasia be pathologic? Give an example
If the growth mechanisms lose their control; i.e. cancer
42
What are 6 causes of atrophy?
1) Decreased workload
2) Loss of innervation
3) Diminished blood supply
4) Inadequate nutrition
5) Loss of endocrine stimulation
6) Aging [of the brain]
43
Define metaplasia and give 2 examples
1) Change in cell type
2) Smoker's bronchi & Barret's esophagus
44
Metaplasia can lead to what?
Dysplasia
45
1) Dysplasia refers to what?
2) What are the 2 aspects of it?
1) Disorderly proliferation of cells
2) -Uniformity
-Polarity/orientation
46
True or false: Dysplasia does not indicate cancer, though it is on the pathway to becoming cancerous
True
47
True or false: Hyperplasia alone is not enough to cause cancer
True
48
List the steps of coagulative necrosis
1) Ischemia/Infarct
2) Drop in ATP production
3)Glycogen supply allows for anerobic metabolism
4) Late stage = membrane bound organelles burst
5) Cell ruptures
49
Coagulative necrosis:
1) When does ischemia/ infarct usually occur?
2) What does a drop in ATP production lead to? What does this then cause?
1) Occurs in places with stores of glucose)
2) Na/K pumps fail
Cell swells > pale and firm gross appearance
50
Coagulative necrosis:
1) What does glycogen supply allow for? What does this produce?
2) What does this do to pH? What does this cause?
1) Allows for anerobic metabolism; lactate is produced
2) pH falls; proteins are denatured!
51
Coagulative necrosis:
1) What happens during the late stage? What doesn't happen?
2) What happens when the cell ruptures?
1) Membrane bound organelles burst; lysosomes spill their contents
-Lysis of cellular architecture does not occur
2) Ca enters the cell; macrophages and neutrophils flood in; inflammation ensues
52
Liquefactive necrosis:
1) What causes it?
2) Does this affect pH? Explain
1) CNS infarct/ Pyogenic Infxn
2) CNS is highly active tissue and glucose/glycogen poor
-Thus, no anerobic metabolism; pH does not fall
53
Liquefactive necrosis:
1) Do ATP pumps fail? Does the cell swell?
2) Do the organelles rupture?
1) ATP pumps still fail and cell swells
2) Organelles rupture; lysosomes spill their contents
54
Liquefactive necrosis:
1) Are the enzymes still active after lysosomes spill their contents? Explain
2) What happens in a pyogenic infection?
3) What does this look like on microscopy?
1) Enzymes are all active; you get cellular soup!
2) Neutrophils / bacteria emit lytic enzymes
3) Soupy vacuoles give “moth eaten” appearance
55
Caseous necrosis:
1) What organism can do this?
2) What is a granuloma?
3) What happens within the granuloma?
4) What do they look like?
1) TB (& maaaaybe fungus)
2) “Walling off” of infected area by macrophages
3) They attempt to destroy everything inside their perimeter
4) Pink patches surrounded by blue nuclei of macrophages
56
Fat Necrosis:
1) What are the two causes?
2) How are pancreatic enzymes involved?
3) What happens after the pancreatic enzymes do their thing?
4) What does this look like on microscopy?
1) Enzymatic or traumatic
2) Adipose tissue contains triglycerides which are dismantled by pancreatic enzymes
3) Calcium binds; Salt + lipids = soap “saponification”
4) White spots are noted on gross evaluation and upon microscopy
57
List 2 key signs of necrosis and give examples
1) Increased eosinophilia
2) Nuclear changes: Pyknosis, Karyorrhexis, Karyolysis
58
Nuclear changes during necrosis:
1) Define Pyknosis
2) Define Karyorrhexis
3) Define Karyolysis
1) Pyknosis: nuclear shrinking and increased basophilia – DNA is dark, shrunken mass
2) Karyorrhexis: nucleus starts to fragment
3) Karyolysis: nucleus breaks apart totally and DNA is broken down by DNase
59
Coagulative necrosis cell fate:
1) Does the cell completely digest itself?
2) What is recruited?
3) What digests cells?
4) What removes debris?
5) What does it look like on a patient?
1) Cell does not digest itself completely
2) Leukocytes are recruited
3) Cells are digested by their lysosomal enzymes
4) Debris is removed by phagocytosis mediated by infiltrating neutrophils and macrophages
5) Dry gangrene
60
Liquefactive Necrosis cell fate:
1) Does the cell completely digest itself?
2) What does it look like on a pt?
1) Dead cells are completely digested, leaving creamy yellow liquid eventually to be removed by phagocytes
2) “Wet” gangrene
61
slide 44
Caseous Necrosis cell fate:
1) What
1)
2) “Granuloma"
62
Fate of Fat Necrosis:
1) What is this usually?
2) What causes it?
3) What does this result in?
1) Pancreatitis
2) Enzymes released from acinar cells liquify fat cells in the peritoneum
3) Lipases split triglyceride esters that combine with Calcium; **“saponification”**
63
Describe the fate of cells in fibrinoid necrosis
1) Immune reactions in which complexes of antigens and antibodies are deposited in vessel walls
2) Bright, pink amorphous appearance
3) Polyarteritis nodosa
64
True or false: often cellular damage can be located by tests with specificity for the affected organ bc of the release of intracellular proteins
True
65
What are the necrosis biomarkers for:
1) Cardiac muscle
2) Hepatic duct epithelium
3) Hepatocytes
1) Enzyme creatine kinase, contractile protein troponin
2) Alkaline phosphatase
3) Transaminases
66
1) Define apoptosis
2) Why is it called apoptosis?
3) Is it controlled? Is there inflammation?
1) Controlled dismantling of the cell
2) “Edible” Fragments of apoptotic cells break off ; “apoptosis” means falling away
3) Done in a controlled manner, without the intracellular contents spilling out; therefore, there is not much inflammation caused
67
List and define the 2 categories of apoptosis and give examples
1) Physiologic apoptosis: When cells need to die as a part of normal embryonic development
-In the immune system, when lymphocytes recognize self-antigens and must be purged
2) Pathologic apoptosis: When the cell is damaged severely and irreversibly and must be “taken out”
-This could be due to severe damage or the emergence of cancer
68
List and define the 2 *pathways* of apoptosis
1) Intrinsic
The cause of most physiologic and pathologic apoptosis, involving the mitochondria in initiating apoptosis sequence
2) The Death Receptor pathway
Cells express antigens on their surface that trigger apoptosis
69
1) What do both apoptosis pathways lead to?
2) What are these? List and describe the 2 kinds
1) Both lead to the initiation of “CASPACES”
2) Proteins:
Initiator – caspases 8,9
Effector – caspase 3
70
Intrinsic pathway of apoptosis:
1) What do mitochondria contain inside their lipid bilayer?
2) What does this do when it gets out?
1) Cytochrome C
2) Initiates CASPACES
71
What keeps cytochrome C inside the cell under normal circumstances?
It’s actually the cell’s default to release it!
It depends on a constant signal from outside the cell, saying “don’t self destruct”; BCL-2 is a protein that’s created to bind with Bax forming a heterodimer, keeping the “door” from coming together and letting out cytochrome C
72
Intrinsic pathway of apoptosis:
1)There is a “door” on mitochondria created by Bax bak homodimer that ushers _______________ out of the cell
2) Unless what?
1) cytochrome C
2) Unless the cell stops this sequence.
73
1) What protein keeps cells form self destructing all the time? What is it bound to and what does this form?
2) What "keeps the door separated" metaphorically?
1) BCL-2; created to bind with Bax forming a heterodimer, keeping the “door” from coming together and letting out cytochrome C
2) Growth factors at the surface of the cell – saying “don’t die
74
What key 3 things start the intrinsic pathway of apoptosis?
1) Planned death as a part of embryonic development
2) Failure to receive external signals from outside the cell that prevent destruction
3) P53 tumor suppressor activity
75
P53 tumor suppressor gene creates what?
P53 protein
76
What are 3 things P53 protein can do?
1) Low concentrations of P53 initiate DNA repair mechanisms
2) Medium concentrations of P53 arrest cellular reproduction
3) High concentrations of P53 induces the production of BAD > BCL2 > bax/bak > lets out Cytochrome C > initiates CASPACES 8,9 > 3
77
1) What gets P53 started?
2) Why would this occur?
1) Increased concentrations of misfolded proteins in the Endoplasmic reticulum
2) Mutation
78
Extrinsic pathway of apoptosis:
1) What starts this?
2) What is this called? What are the 2 main types?
1) A cell that has been designated for apoptosis presents an antigen that is recognized by the immune system as marking the cell for self destruction
2) "Death receptor”; TNF-alpha, and Fas Fas ligand
79
Extrinsic pathway of apoptosis:
1) When these receptors are expressed on the surface of the cell, they initiate a sequence of the CASPASE cascade; what is it?
2) What is this process mostly limited to?
1) 8,9 > 3 > self destruct
2) The death of self-reactive T cells in the thymus
80
List causes of inflammation (hint: similar to causes of cell injury)
1) Infections: Bacterial, viral, fungal, parasitic
2) Microbial toxins as well
3) Tissue necrosis
4) Foreign bodies
5) Immune reactions - hypersensitivity
81
What 2 big things happen when inflammation starts? What does each mean?
1) You get more fluid to the area; vascular changes
2) Your body’s cells “go to war”; cell and protein mediated destruction
82
Inflammation; Recognition:
Microbes and necrotic cells are recognized by what 3 things? What does each specifically do?
1) Primarily antigen presenting cells = Foreign invaders from outside of the cell
2) Internal stimuli within the cell > signal cellular distress
3) Circulating proteins that indicate that damage has occurred
83
List the 6 stages of inflammation
1) Recognition of threat
2) Response of vascular tissues to insult
3) Recruitment of leukocytes and plasma proteins
4) Destruction of offending substance
5) Termination of sequence
6) Repair of damaged tissue
84
During the first step of Recognition (Foreign Invaders):
1) What two cells express receptors that detect the presence of infectious foreign invaders
2) What happens when these receptors are activated?
1) Phagocytes + dendritic cells (both designed to capture foreign invaders)
2) They trigger the secretion of specific proteins
85
When these receptors for foreign invaders are activated, they trigger the secretion of 3 specific proteins; what are they?
1) Cytokines that produce inflammation
2) Anti-viral cytokines (interferons)
3) Cytokines and membrane proteins that activate lymphocytes
86
Step 2 of Recognition (Internal Cellular sensors of Cell Damage): Where can signals that things have gone awry within the cell be found?
Inside the cytosol
87
Step 2 of Recognition (Internal Cellular sensors of Cell Damage): Inside the cytosol, there are signals that things have gone awry within the cell, what are they? (4) and explain each
1) Uric acid build up: product of DNA breakdown
2) ATP: in reduced amounts of this signals damaged mitochondria
3) Reduced intracellular K+ indicates loss of ions because of damaged cell membrane
4) DNA: when found in the cytoplasm indicates damaged nucleus
88
Step 2 of Recognition (Internal Cellular sensors of Cell Damage):
1) What are the signs that things have gone poorly inside the cell called?
2) What do they do?
3) What does this then do?
1) “DAMPs” (damage-associated molecular patterns)
2) Activate a multiprotein cytosolic complex called the inflammasome
3) Recruits leukocytes and induces inflammation
89
1) In step 3 of Recognition (Circulating proteins), what system is used? What does it react against and produce? 2) Why?
1) Compliment system: Reacts against microbes and produces mediators of inflammation
2) Lysis of infectious organisms
-Activation of further inflammatory cells
-Opsonization of targeted agents
90
The first step of inflammation is recognition. What are the 3 steps of recognition?
1) Foreign Invaders
2) Internal Cellular sensors of Cell Damage
3) Circulating proteins
91
What are the two major steps of inflammation?
1) Increases blood flow (vasodilation)
2) Makes vessels more permeable (permeability)
92
P53 tumor suppressor gene creates what?
P53 protein
93
What are 3 things P53 protein can do?
1) Low concentrations of P53 initiate DNA repair mechanisms
2) Medium concentrations of P53 arrest cellular reproduction
3) High concentrations of P53 induces the production of BAD > BCL2 > bax/bak > lets out Cytochrome C > initiates CASPACES 8,9 > 3
94
1) What does the increase in permeability and vasodilation during inflammation lead to?
2) Define exudate
1) The escape of fluid proteins and blood cells from the vascular system into the interstitial tissues or body cavities
2) Has high protein concentration and contains cellular debris
95
1) Describe the properties of transudate
2) What is this a result of?
1) Transudate by contrast has low protein content, little cellular material, low specific gravity
2) Osmotic pressure or hydrostatic imbalance across vessels with normal permeability
96
What are 2 ways permeability of vessels can change? Specify which is the result of damage and which is physiologic
1) Inflammatory rxn: physiologic
2) Endothelial injury: damage
97
1) What change in permeability can be thought of as vascular leakage?
2) What is released, what is retracted, and what does this open?
1) Inflammatory rxn: physiologic
2) Release of histamine (bradykinin, leukotrienes)
Retraction of endothelial cells >
Opening of inter-endothelial spaces
98
1) What does Endothelial injury (damage) come from?
2) What does it lead to?
3) When does it stop?
1) Results from tissue damage like microbe infestation, burns, etc.
2) Cell necrosis and detachment which is sometimes made worse by the attachment of neutrophils
3) Continues until the vessels are thrombosed or repaired
99
1) Why do lymph vessels become involved in inflammation?
2) What may become secondarily inflamed and what can this lead to?
1) They are set up to drain away extravascular fluid and its contents
2) Lymphangitis, leading sometimes to inflammation and enlargement of the nodes; lymphadenopathy
100
1) What accounts for tumor, rubor, and calor of inflammation?
2) What causes color of inflammation?
1) Blood and fluid to the area
2) Increased bradykinin, leukotriene, histamine
101
What does recruitment largely refer to?
Recruiting WBCs
102
What are 3 steps of leukocyte involvement?
1) Adhesion and margination
2) Migration diapedesis
3) Chemotaxis
103
Leukocyte involvement in inflammation: Adhesion and margination:
1) Usually, leukocytes are moving to quickly through vessels to attach to the walls and move through, but what would make this possible?
2) What help the leukocytes to adhere to the cell walls?
3) What are 2 molecules that help in this process at the micro level?
1) Reduced blood flow
2) Endothelial cells are activated by cytokines that help the leukocytes to adhere to the cell walls
3) Selectins and integrins
104
Leukocyte involvement:
1) What is migration diapedesis?
2) What is chemotaxis? Give examples
1) Move through the cell wall – transmigration
2) Chemoattractants actually move the leukocytes to the battle site
-Bacterial products
-Cytokines
-Complement system
-Lipoxygenase of arachidonic acid – leukotriene
105
True or false: Leukocytes that are recruited to sites of inflammation perform the key function of eliminating the offending agents.
True
106
Most important leukocytes in inflammation are the ones capable of phagocytosis; what are these? Describe their response times and what makes them unique
1) Neutrophils: rapid, transient response
2) Macrophages: slower, but more prolonged response
-Macrophages also produce substances that aid in tissue repair
107
1) What are leukocytes responsible in doing with inflammation?
2) Why do they cause collateral damage?
1) Ingest or destroy bacteria and other microbes, as well as necrotic tissue and other substances
2) Increased potency of these leukocytes, may induce prolonged inflammation and collateral host tissue damage
108
1) _______________ last longer and are slower to arrive, eventually support collagen formation, which adds to the changes of chronic inflammation
2) _________________ come faster and live longer, do more destruction at the site of acute inflammation – sometimes with negative effect
1) Macrophages
2) Neutrophils
109
1) How long do neutrophils stick around?
2) What abt macrophages?
1) 6-24 hours
2) 24-48 hours
110
What are the 3 outcomes of acute inflammation?
1) Complete resolution
2) Healing by connective tissue replacement (scarring or fibrosis)
3) Chronic Inflammation
111
Define chronic inflammation
Response to prolonged duration (weeks to months) in which inflammation, tissue injury, and attempts at repair coexist in varying combinations
112
Inflammation Destruction, Termination, Repair stages:
From this point, the body’s inflammatory response will either destroy the source of inflammation, or not. Describe each outcome.
1) If the offending agent is not destroyed, the inflammation may become chronic
2) If it is, then repair mechanisms and tissue healing can take place
113
Recap:
1) True or false: Inflammation is a beneficial host response to foreign invaders
2) What are the 2 main parts?
3) What are the steps of inflammation?
1) True
2) Vascular reaction and cellular response
3) Steps of inflammation: R’s: Recognition, recruitment of leukocytes, removal of the agent, regulation of the response, resolution and repair
114
Recap:
1) What are some causes of inflammation?
2) What 3 things all express receptors that sense the presence of microbes and necrotic cells?
1) Infection, tissue necrosis, FB, trauma, immune response (see prior list)
2) Macrophages, and dendritic cells, leukocytes
115
1) What do circulating proteins do?
2) What is the outcome of acute inflammation?
1) Recognize microbes in the blood
2) Either elimination of offending agent followed by decline of inflammation, or chronic inflammation
116
1) Vasodilation is induced mostly by what? What does this act on?
2) What is vasodilation one of the earliest manifestations of? What does it lead to?
3) Vasodilation is followed by increases in what 2 things?
1) Histamine released by mast cells; vascular smooth muscle
2) One of the earliest manifestations of acute inflammation; increases flood flow
3) Increased permeability and exudative fluid
117
The use of prostaglandin inhibitors has two major side effects; what are they?
1) Peptic ulcer
2) Acute and chronic kidney disease
118
1) What is serous inflammation?
2) Describe it
*not emphasized in class*
1) Exudation of cell poor fluid (“watery”) into spaces:
2) Created by injury to surface epithelium; fluid accumulates in body cavities lined by peritoneum, pleura, or pericardium
119
Fibrinous Inflammation is a hallmark of what?
*not emphasized in class*
Develops when:
-Vascular leaks are large
-Local procoagulant stimulus
-Occurs when there is more severe inflammation
-Fibrinogen passes through the vessels
-A hallmark of chronic inflammation!
120
Describe purulent (suppurative inflammation)
*not emphasized in class*
Large amounts of purulent exudate (pus)
Neutrophils, liquified debris of necrotic cells, edema
121
What are ulcers?
*not emphasized in class*
Local defect of excavation, of the surface of an organ or tissue that is produced by the sloughing of inflamed necrotic tissue
MC in Mouth/GI tract or skin/sub q tissue
122
slide 123
123
List some signs of systemic inflammation
1) Fever; pyrogens incl. exogenous pyrogens
2) C-reactive proteins and fibrinogen
3) Leukocytosis; left shift
124
List some other signs of systemic inflammation
1) Increased HR
2) Decreased BP
3) Decreased sweating
4) Rigors
5) Chills
6) Anorexia
7) Somnolence
8) Malaise
125
Septic shock:
1) What causes it?
2) What can it progress to?
1) Large amounts of bacteria stimulate massive quantities of cytokines, particularly
2) DIC, hypotensive shock
126
What two treatments mediate fever?
NSAIDS (turn down prostaglandins) and Tylenol
127
What are the 2 mechanisms of tissue repair?
Regeneration or Scar
128
1) The main phases of cutaneous wound healing are what?
2) Cutaneous wounds can heal in what 2 ways?
1) Inflammation, formation of granulation tissue, and ECM remodeling.
2) Primary union (first intention) or secondary union (secondary intention); secondary healing involves more extensive scarring and wound contraction.
129
1) Wound healing can be altered by many conditions, particularly what? Explain
2) What can cause keloids in the skin?
3) What does persistent stimulation of collagen synthesis in chronic inflammatory diseases lead to?
1) Infection and diabetes; the type, volume, and location of the injury are important factors that influence the healing process.
2) Excessive production of ECM
3) Tissue fibrosis, often with extensive loss of the tissue and functional impairment.
130
Factors that interfere with healing may be __________ (e.g., infection) or ____________ to the injured tissue
extrinsic or intrinsic
131
List some factors that can inhibit tissue repair
1) Infection
2) Diabetes
3) Nutritional status
4) Glucocorticoids (steroids)
5) Mechanical factors
6) Poor perfusion
7) Foreign bodies
8) The type and extent of tissue injury
9) Location of the injury and the character of the tissue
132
1) The 3 main phases of cutaneous wound healing are what?
2) Cutaneous wounds can heal by primary union or secondary union; what are these also called?
3) Excessive production of ECM can cause __________ in the skin.
1) Inflammation, formation of granulation tissue, and ECM remodeling.
2) First and second intention
3) keloids
133
Persistent stimulation of __________ synthesis in chronic inflammatory diseases leads to tissue fibrosis, often with extensive loss of the tissue and ____________________
collagen; functional impairment.
134
List 2 causes of cellular aging and give examples if possible
1) Accumulations of errors in DNA
-ROS (reactive oxygen species), Mutations
2) Decreased cellular replication: Cells have a limited capacity for this
135
1) Define Intracellular Accumulations
2) Give examples
1) Build up of various substances
2) Steatosis- triglycerides
-Cholesterol
-Proteins
-Glycogen Pigments (exogenous or endogenous)
136
What are the 2 types of glycogen pigments? Give examples
Exogenous: carbon
Endogenous: lipofuscin, melanin, hemosiderin
137
What can cause fatty liver changes?
Alcohol abuse, diabetes with obesity, NASH (non-alcoholic steatohepatitis)
138
1) What is an example of an exogenous carbon buildup?
2) What is lipofuscin?
1) Anthracosis; Coal miner’s lung
2) Yellow-brown pigment; Free-radical peroxidation of membrane lipids
“Wear and tear pigment”
139
Give an example of calcification
Aortic valve
140
1) When its time to self destruct, The BAD protein is produced which binds to what?
2) What does this allow?
3) What does this ultimately let out?
1) BCL-2
2) Bax bak door to come together and let out
3) Cytochrome c CASPACES 8,9 3
141
Give a summary of the intrinsic pathway of apoptosis
1) Programed death as a part of embryonic development
2) Loss of growth factors at cell membrane
Inhibition of BCL2 through BAD protein pairing> Bax/Bak dimer > Cyt C ? CASPASE 8,9 > CASPASE 3 >
3) Genetic mutation leading to DNA damage or bad protein product
-A little bit of P53 = DNA repair mechanisms
-A moderate amount of P53 = DNA repair + arrest cell cycle
-A lot of P53 > BAD binds to BCL2 = Bax/Bak dimerize = Cyt C leaves mitochondria > CASPASES 8,9 CASPASE 3 >
142
Give a summary of the extrinsic pathway of apoptosis
Self-reactive T cell presents antigen to death receptor (TNF-alpha, Fas Fas) > CASPASE cascade > CASPASE 3 > apoptosis
143
1) After vasodilation is followed by increased permeability and exudative fluid, what does this eventually lead to?
2) What happens at this point?
3) What does this cause? (actually and visually)
1) Exudate build up in the extravascular tissues
2) Blood flow slows now
3) Vessels become engorged with slow moving red cells
-What we see up on gross inspection is erythema
144
True or false: Leukocytes as a whole can do more harm than good in some disease. Explain or give examples.
True; TB, hepatitis, both with prolonged host response does more damage than the microbe
145
How can leukocytes sometimes do more harm than good?
1) Granule enzymes and anti-microbial proteins may be released into the extracellular environment.
2) The mechanisms that function to eliminate microbes and dead cells (the physiologic role of inflammation) also are capable of damaging normal tissues (the pathologic consequences of inflammation)
146
Differentiate between acute and chronic inflammation
1) **Acute: Occurs in minutes to hours and lasts from hours to days**
-Exudation of fluid and plasma proteins – causing edema
-Emigration of leukocytes, mostly neutrophils (PMNs) + macrophages (to a lesser degree)
2) **Chronic: Longer duration**
-Associated with more tissue destruction
-Presence of macrophages
-Proliferation of blood vessels
-Fibrosis
147
Acute vs chronic inflammation:
1) Which involves fibrosis?
2) Which is assoc. with more tissue destruction?
3) Which is marked by the emigration of mostly neutrophils (PMNs) and macrophages?
1) Chronic
2) Chronic
3) Acute
