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Minarcik robbins 2013_ch2-inflam
1.
2. CHAPTER 2
Inflammation
(5 OBJECTIVES)
1) (Concept) Understand the chain,
progression, or sequence of
vascular and cellular events in
the histologic evolution of acute
inflammation
3. 2) (Rote?) Learn the roles of various
“chemical mediators” of acute
inflammation
3) Know the three possible outcomes of
acute inflammation
4) Visualize the morphologic patterns of
acute inflammation
5) Understand the causes, morphologic
patterns, principle cells, minor cells, of
chronic and granulomatous
inflammation
4. SEQUENCE OF EVENTS
•
•
•
•
•
•
•
•
•
NORMAL HISTOLOGY
VASODILATATION
INCREASED VASCULAR PERMEABILITY
LEAKAGE OF EXUDATE
MARGINATION, ROLLING, ADHESION
TRANSMIGRATION (DIAPEDESIS)
CHEMOTAXIS
PMN ACTIVATION
PHAGOCYTOSIS: Recognition, Attachment,
Engulfment, Killing (degradation or digestion)
• TERMINATION
• 100% RESOLUTION, SCAR, or CHRONIC
INFLAMMATION are the three possible outcomes
32. CYTOKINES/CHEMOKINES
• CYTOKINES are PROTEINS produced by
MANY cells, but usually LYMPHOCYTES
and MACROPHAGES, numerous roles in
acute and chronic inflammation
–TNFα, IL-1, by
macrophages
• CHEMOKINES are small proteins which are
attractants for PMNs (>40), e.g., CXC, CC,
CX3C, XC families, PF-4, IL-8
33. NITRIC OXIDE
• Potent vasodilator
• Produced from the action
of nitric oxide synthetase
from arginine
34. LYSOSOMAL CONSTITUENTS
• PRIMARY
• SECONDARY
• Also called
AZUROPHILIC, or
NON-specific
• Also called SPECIFIC
• Myeloperoxidase
• Lysozyme (Bact.)
• Acid Hydrolases
•
•
•
•
Lactoferrin
Lysozyme
Alkaline Phosphatase
Collagenase
35. FREE RADICALS
• O2 – (SUPEROXIDE)
• H2O2 (PEROXIDE)
• OH- (HYDROXYL RADICAL)
•
VERY VERY DESTRUCTIVE
The sequence of changes occurring in acute inflammation are NOT specific for the stimuli which cause them
These are the three “phases”, in order, of acute inflammation. Please NOTE they, in no way, are the independent of each other, and as you might suspect by now, quite the contrary, CRUCIALLY all wrapped up with each other!
Many names, same cell
The four “cardinal”, i.e., “classic” signs of inflammation, translated, literally, 1) redness, 2) heat, 3) swelling, 4) pain.
Just like a fith Marx bother, Gummo, was often added, so was the term “functio laesa” or “loss of function”
The usual suspects, again. “Stimuli”, like “etiologic agents” is a very elusive term if you like to think in terms of ultimate causes.
Vascular changes occur BEFORE any infiltration of inflammatory cells arrive.
These are all events which either cause, or result, from the phenomenon of “increased permeability”
Transudate vs. Exudate. Transudates can be thought of as being fairly pure water. Transudates are water PLUS most serum proteins, fibrin, and many blood cells often. So which one do you think requires bigger holes in the endothelium, transudates or exudates?
The four things neutrophils do, in order, in acute inflammation. This is beautifully demonstrated in live cell imaging!
Secretins and integrins are classes of substances to help neutrophils stick to vessel walls and migrate through the wall. Yes they are CAMs.
CHEMOkines induce CHEMO-taxis, that why their called CHEMO-kines.
These three events are the results of leukocytes (i.e., neutrophils) being “activated”
The three phases of phagocytosis, in correct order. 1) Recognition2) Engulfment3) Digestion (cell probably already dead)
These are the common features of ALL “chemical mediators” in acute inflammation. This is the shovelling part!
How many of the 4 cardinal signs of inflammation can histamine cause, by virtue of its being a powerful vasodilator? 3-4?
Serotonin is widely and primarily thought as being a neurotransmitter involved in the full spectrum of emotional responses, but its role in acute inflammation is just as powerful.
Complement fixation is the end stage of a cascade of multiple chemical events, similar to coagulation, which ultimately result in lysis of cell membranes, hopefully, membranes of bad cells.
Bradykinin is a potent endothelium-dependent vasodilator, causes contraction of non-vascular smooth muscle, increases vascular permeability and also is involved in the mechanism of pain.
Coagulation is also a cascade, like complement fixation.
Three classic eicosanoids, new classes are also being discovered. ALL are derivatives from arachidonic acid. Eicosanoids can also be directly attributed to causing the 4 cardinal signs of inflammation. http://en.wikipedia.org/wiki/Eicosanoid
The problem with Eicosanoids is that you NEVER get the BIG picture: Here’s the BIG PICTURE NOW!
Arachidonic acid
When you think of the three main things that ASPIRIN does, you can remember the three main properties of the prostaglandins.
Click back to the previous slide on LEOKITRIENES and realize that LIPOXINS generally do the OPPOSITE of what LEUKOTRIENES do.
It is produced in response to specific stimuli by a variety of cell types, including neutrophils, basophils, platelets, and endothelial cells. From wiki:Platelet-activating factor, also known as a PAF, PAF-acether or AGEPC (acetyl-glyceryl-ether-phosphorylcholine) is a potentphospholipid activator and mediator of many leukocyte functions, including platelet aggregation and degranulation, inflammation, and anaphylaxis. It is also involved in changes to vascular permeability, the oxidative burst, chemotaxis of leukocytes, as well as augmentation of arachidonic acid metabolism in phagocytes.
There are gazillions of cytokines/chemokines. The two most classical and famous ones are TNF-alpha and Interleukin-1.
TNF-alpha, also called tumor necrosis factor, or cachectin, is a substance that is destructive of human tissues, and is a key player in “cachexia”.
Interleukin-1 was the first of many interleukins discovered and generally propagates the inflammatory response at many levels and also has a significant effect on T-cells.
Which drug INCREASES the effect of nitric oxide? Hint: you get spam ads for it 10 times a day in your spam, even if you are a female.
MPO produces hypochlorous acid and tyrosyl radical are cytotoxic, so they are used by the neutrophil to kill bacteria and other pathogens. It is what makes pus look greenish yellow.
Lactoferrin (LF), also known as lactotransferrin (LTF), is a globular multifunctional protein with antimicrobial activity (bacteriocide, fungicide)
Lysozymes, also known as muramidase or N-acetylmuramide glycanhydrolase, are a family of enzymes (EC 3.2.1.17) which damage bacterial cell walls by causing hydrolysis.
Free radical are generated through a variety of enzymatic pathways as one of the main killing mechanisms of microbes. Free radicals themselves are just as toxic to human cells as they are microbes. Ultimately, they all affect the NADPH system.
Substance P is an 11 amino acid polypeptide tied into many things including mood disorders, anxiety, stress, reinforcement, respiration rate, neurotoxicity, nausea, emesis, and pain. The Neurokinins are also peptide neurotransmitters involved in many things.
Three classic outcomes of acute inflammation
FOUR patterns of acute inflammation:
(OneLook.com has 133 adjectives to the word “inflammation”)
FIBRIN is the endpoint of coagulation and had a characteristic appearance both grossly and microscopically. Do you remember hearing the term fibrin-OID necrosis too?
It is EXTREMELY important to be able to recognize neutrophils (Polys) in H&E sections. The key tip is, OFTEN, they might NOT look multilobulated at first, but upon close examination, they are!
ULCERS (i.e., pathologic LOSS of mucosal or epithelial coverings, are both the CAUSE as well as a RESULT of acute inflammation. WHY? Identify the FOUT layers of the colon here, mucosa, submucosa, muscularis, and finally adventitia/serosa.
If there was only ONE slide you needed to memorize for this chapter, THIS would be it!
Please understand the DIFFERENCE between a MONO-cyte, and a generic MONO-nucleated cell.
What does chronic inflammation look like? ANS: Infiltrates of lymphs and monos “peppering” normal histology.
Most auto-immune inflammations are long standing, or “chronic” clinically as well.
Please note that the “cellular” players of chronic inflammation are NOT the baseball players who play in US Cellular Field in Chicago, i.e., the White Sox.
Know, ALWAYS, the FOUR cells of granulomatous inflammation, and the FOUR common types of granulomatous infections: 1) TB, 2) Sarcoid, 3) Fungi, 4) Foreign Bodies.
Why do granulomas form, rather than just acute or chronic inflammation? Very simple, you need to bring your friends if your enemy is too big?
The drainage patters of acute or chronic inflammation follow the same general drainage patterns of tumor cells.
CRP is a member of the class of acute phase reactants as its levels rise dramatically during inflammatory processes occurring in the body. It is thought to assist in complement binding to foreign and damaged cells and affect the humoral response to disease. It is also believed to play an important role in innate immunity, as an early defense system against infections.
Which TWO of these 5 “hills” are significantly higher in nonspecific systemic acute inflammation?
Answer: alpha-1 and alpha-2
