Lecture 2 Flashcards
(28 cards)
What is inflammation
Where in the body can inflammation not occur?
Response or vascularized tissues that delivers leukocytes and molecules of host defense from circulation to the sites of the infection and cell damage in order to eliminate the offending agents
Cartilage also doesn’t have blood vessels supplying it
Inflammation can occur everywhere cuz there is blood supply to every part of the body. But there are two places that are not supplied with blood vessels . The testes in males and the cornea in the eye.
State the five cardinal signs of inflammation
Redness-rubor(due to presence of many red blood cells at the site)
Heat-Calor(due to presence of many red blood cells at the site)
Swelling-tumor (due to leakage of fluid into tissues from blood vessels cuz the blood vessels have become leaky)
Pain-dolor(pain cuz of the swell in which will compress the nerve endings there and also due to release of prostaglandins during inflammation)
Loss of function -functio laesa (all the above lead to loss of function)
The upper four are due to changes in the blood vessels supplying the site where the inflammation is to take place and the last one is due to the first four.
Who is the founder of pathology
Who discovered phagocytosis?
Rudolf virchow (1821-1902)(he brought about inflammation)
Phagocytosis-
Elie Metchnikoff (1845-1916)
The name “Elie Metchnikoff” is the French transliteration of his original Russian name, Илья Ильич Мечников (“Ilya Ilyich Mechnikov”). In English, he is often referred to as Elie Metchnikoff, but “Ilya Mechnikov” is also correct and commonly used,
What are the components of inflammation?
Inducers-infectious agents and pathogens,immune cells,foreign body causing tissue damage
Sensors- cells in body that pick up or sense the inducers in the body(mast cells,dendritic cells,macrophages)
Mediators-the sensors release mediators which effect certain responses within the body and bring an effect on the target tissues(TNF,IL-1,IL-6,CCL2,CXCL8,Histamine,Bradykinin,Eicosanoids)
Target tissues
State four causes of inflammation
● Infections
● Tissue necrosis(remember that apoptosis won’t lead to inflammation cuz it’s a programmed cell death)
● Foreign bodies
● Immune reactions
All immune cells have pattern recognition receptors. Example is Toll like receptors (TLRs)
What is PAMP?
What is DAMP?
Which is found in necrotic cells?
Which is found with infectious agents?
What is the main function of this PAMP AND DAMP
What is the end result of the function of PAMP AND DAMP in inflammation?
What is the function of Toll like receptors?
Between PAMP and DAMP, which do Toll like receptors recognize more?
These are made to identify PAMPs (Pathogen-Associated Molecular Patterns. These are found with infectious agents) and DAMPs (Damage-Associated Molecular Patterns. These are usually found in necrotic cells). The PAMPS AND DAMPS are molecules that play crucial roles in the immune system by alerting the body to the presence of infections or cellular damaged.
This entire thing leads to events which affect nuclear synthesis of certain inflammatory cytokines inside the cell that got into contact with the infectious agent. This leads synthesis of inflammatory cytokines which are released into the surroundings
Toll like receptors are like intracellular proteins in the cell and it transmits the information (signal transduction) it gets when it comes into contact with either PAMP or DAMP depending on the agent causing the inflammation. This leads to signals entering the nucleus of the cell causing promotion of synthesis of inflammatory cytokines.
So infectious agent-PAMP-Toll like receptors recognize PAMP-this leads to inflammatory cytokines release
TLR recognize PAMPS more than DAMPS while NOD Like receptors (NLR) recognize both PAMPS and DAMPS more
ocation
- NLRs (NOD-like receptors):
- Intracellular: NLRs are located within the cytoplasm of cells, where they detect intracellular pathogens and cellular damage.
-
TLRs (Toll-like receptors):
- Extracellular and Endosomal: TLRs are found on the cell surface and within endosomal compartments. They recognize extracellular and endosomal PAMPs.
State the steps of inflammatory reaction
Recognition (TLL and NLR recognizing PAMPS or DAMPS)
● Recruitment(recruitment of cells which will help in inflammatory pathways. This leads to synthesis of mediators or inflammatory cytokines. Mediators will cause recruitment of leukocytes which will try to remove the pathogens )
● Removal-the recruited leukocytes remove the pathogens
● Regulation-regulate their activities at the site of inflammation
● Repair-initiate repair of the tissue
I hat are the components of acute inflammation
Note:there is brief vasoconstriction in acute inflammation followed by a longer period of vasodilation
Vascular component;Dilation of small vessels leading to increase in blood flow. There is also stasis in blood flow
Cellular component: Increased permeability of the microvasculature enabling plasma proteins and leukocytes to leave the circulation.
Emigration of leukocytes from the microcirculation of their accumulation in the focus of injury and their activation to eliminate the offending agent. The stasis of blood allows wbcs to come out and align themselves on the inner endothelium of blood vessels.
So when they come and align, they roll by selectins and then adhere to the endothelium lining by integrins. The adhesion makes them tightly bound to the lining so that blood won’t move them from there and they’ll have enough time to respond to the cytokines to know where they’re going to.
So
The increased blood vessel permeability causes increased gaps in the endothelial lining so that the leucocytosis can move through these gaps
And into the tissue. This is transmigration or diapedesis.
When they go into the tissue, they follow the signals and get to the site of infection. This is chemotaxis
State four differences between acute and chronic inflammation
Onset
Acute Fast: minutes or
hours
Chronic Slow: days
Cellular infiltrate:
Acute-Mainly neutrophils
Chronic-Monocytes/macrophages and lymphocytes
Tissue injury, fibrosis:
Acute- Usually mild and self-limited
Chronic-Often severe and progressive
Local and
systemic signs:
Acute-Prominent
Chronic -Less
Inflammation is more in acute than in chronic.
How is transudate and exudate formed?
In inflammation you have more of exudate.
Exudate is high in protein
Some cases, you may have transudate. The transudate is believed to just be a step toward exudate in inflammation cuz transudate is seen when there is dilation of the blood vessels without increased permeability of the blood vessel but once the vessels enlarge more, there is increased permeability and leukocytes, complement proteins,cytokines,etc seeping out of the blood vessels and into the site where the wound is.
Transudate and exudate are two types of fluid that can accumulate in body cavities, often as a result of different pathological processes. Here are the key differences:
-
Origin:
- Transudate: Formed due to systemic factors that alter the balance of pressures within blood vessels, such as increased hydrostatic pressure or decreased oncotic pressure. Common causes include heart failure, liver cirrhosis, and nephrotic syndrome.
- Exudate: Results from inflammation, leading to increased vascular permeability. Causes include infections, malignancies, autoimmune diseases, and trauma.
-
Protein Content:
- Transudate: Low protein content (usually less than 3 g/dL).
- Exudate: High protein content (usually more than 3 g/dL).
-
Cell Count:
- Transudate: Low cell count.
- Exudate: High cell count, often containing inflammatory cells.
-
Specific Gravity:
- Transudate: Low specific gravity (less than 1.012).
- Exudate: High specific gravity (greater than 1.020).
-
Appearance:
- Transudate: Clear and pale.
- Exudate: Cloudy or turbid, often with a yellowish color.
-
LDH (Lactate Dehydrogenase) Levels:
- Transudate: Low LDH levels.
- Exudate: High LDH levels.
These differences help in diagnosing the underlying cause of fluid accumulation and guide appropriate treatment.
What are the vascular changes in acute inflammation
Immediate vasoconstriction
● Vasodilation
● Increased permeability
What are the cellular events changes in acute inflammation
What helps in converting hydrogen peroxide to becoming a harmful ROS?
NADPH helps convert hydrogen peroxide to hypochlorite ion which makes it become more harmful.
NADPH is essential for the initial production of superoxide, which is subsequently converted into hydrogen peroxide and then into hypochlorite(converted to hypochlorite by myeloperoxidase(, a powerful antimicrobial agent, during the immune response.
Recognition
● Emigration (from margination to diapedesis) and chemotaxis
● Phagocytosis
● Killing and degradation
When there is a pathogen, TLL recognize these. Mast cells are recruited and release histamine and kinins which will cause the vascular events that occur in inflammation(vasodilation and increased permeability of vessels). Histamine and kinins also activate the endothelial lining. This activation causes activation of selectins (P and E selectins are in the endothelial lining and L selectin is on leukocytes)
The macrophages that also recognize these cells with the pathogen begin to release inflammatory cytokines(TNF alpha and IL 1).
Transmigration- movement of leukocytes through the endothelial lining to the tissues. They must first break the basement membrane to do this using colagenase.
Movement to site of infection is indicated by IL 8.
Certainly! Here’s a bit more detail:
- Recognition: Immune cells, particularly macrophages and dendritic cells, recognize harmful agents like bacteria or damaged cells through receptors on their surface that detect foreign or abnormal molecules.
- Emigration and Chemotaxis: Upon recognition, immune cells migrate from the bloodstream to the affected tissue. They are guided by chemical signals released by the damaged tissue and inflammatory mediators. This directional movement is called chemotaxis.
- Phagocytosis: Once at the site of injury or infection, immune cells engulf and ingest the foreign invaders or cellular debris through a process called phagocytosis. This involves the formation of pseudopodia that surround and internalize the target.
- Killing and Degradation: Inside the immune cell, the engulfed material is enclosed within a membrane-bound vesicle called a phagosome. This phagosome then fuses with lysosomes, organelles containing enzymes that degrade the engulfed material. Additionally, reactive oxygen species and other toxic substances are produced within the phagosome to kill pathogens.
These cellular events work together to eliminate the source of injury or infection and initiate tissue repair.
Cellular Events in Acute Inflammation
Acute inflammation is a rapid and early response to injury or infection, characterized by a series of specific cellular events:
1. Vascular Changes: • Vasodilation: Increased blood flow to the site of injury, leading to redness (erythema) and heat. • Increased Vascular Permeability: Endothelial cells retract, allowing proteins, fluids, and leukocytes to escape from the bloodstream into the tissue, causing swelling (edema). 2. Leukocyte Recruitment: • Margination and Rolling: Leukocytes (mainly neutrophils) move to the periphery of the blood vessels (margination) and roll along the endothelial surface. • Adhesion: Leukocytes firmly adhere to the endothelial cells via interactions between integrins on leukocytes and adhesion molecules on the endothelium. • Transmigration (Diapedesis): Leukocytes squeeze through gaps in the endothelial lining to enter the tissue. • Chemotaxis: Leukocytes migrate towards the site of injury or infection in response to chemical signals (chemokines). 3. Leukocyte Activation and Phagocytosis: • Activation: Once at the site, leukocytes become activated by various signals (e.g., microbial products, cytokines). • Phagocytosis: Activated leukocytes, primarily neutrophils, engulf and digest pathogens, debris, and dead cells. • Release of Mediators: Leukocytes release various enzymes, reactive oxygen species, and other mediators that contribute to the destruction of pathogens but can also cause tissue damage. 4. Resolution: • In acute inflammation, the response typically resolves once the inciting stimulus is eliminated. Neutrophils undergo apoptosis, and macrophages clear the debris, promoting tissue repair
What are the chemical mediators(not cytokines) in acute inflammation (state five)
What’s the difference between chemical mediators and cytokines
Histamine-released by mast cells
● Arachidonic acid metabolites-contribute to prostaglandin,leukotrienes release
● Platelet-activating factor-the blood in the leaking blood vessels will try to clot due to the leaking in the blood vessels to prevent excessive loss of blood cells
● Cytokines and chemokines
● Complement system
● Kinins-released by mast cells and when released,the kinins release histamines and prostaglandins
● Neuropeptides
Key Differences
• Nature: Cytokines are proteins or glycoproteins, whereas chemical mediators can include a broader range of molecules, such as lipids, amines, and small peptides. • Function: While both are involved in the immune response, cytokines are more specifically involved in regulating and signaling immune cell activities, whereas chemical mediators encompass a wider range of functions, including directly causing vasodilation, increasing vascular permeability, and mediating pain and fever. • Source: Cytokines are predominantly produced by immune cells (like macrophages, T cells, and B cells), while chemical mediators can be produced by a variety of cells and tissues, including endothelial cells, platelets, and the liver (in the case of plasma proteins).
In summary, cytokines are a specific group of chemical mediators that play a central role in immune signaling and regulation, while chemical mediators as a whole encompass a broader array of molecules involved in various aspects of the inflammatory and immune responses.
Why is tuberculosis very difficult to handle?(with regards to what the bacteria does)
Prevents fusion of lysosome and phagocyte to form phagolysosome.
Phospholipase breaks down cell membrane to produce arachidonic acid.
This acid is broken down into either cyclooxygenase or lipooxygenase.
Which pathway produces prostaglandins D,I and E?
Which produces luekotrienes?
Cyclo produces prostaglandins. The prostaglandins cause the pain in inflammation cuz theyre further broken down into substance P(Substance P is a neuropeptide involved in transmitting pain signals and in regulating inflammation)
Lipo produced leukotrienes
How does healing take place in acute and chronic inflammation
Acute: by resolution-clearance of injurious stimuli,clearance of mediators and acute inflammatory cells,replacement of injured cells,normal function
Chronic: fibrosis(deposition of collagen into injured tissues) leading to loss of functions
In normal tissue, collagen is also present as part of the structural framework, but it is not deposited in excessive amounts. Fibrosis specifically refers to the pathological overproduction of collagen in response to injury or chronic damage.
What are the morphological patterns in acute inflammation
Serous inflammation:
outpouring of watery, low-protein fluid
• Fibrinous inflammation:
greater vascular permeability allow fibrin passage(this causes high ESR)
• Purulent (Suppurative) inflammation: produces pus; often due to bacteria
• Ulcers:
• localized areas of necrosis affecting an epithelium, leading to cavity formation.
An ulcer is a localized area of tissue necrosis that occurs when an epithelial surface breaks down. This breakdown typically results from inflammation, infection, or other factors that lead to the death of the epithelial cells. The process usually involves the sloughing off of dead tissue, leading to the formation of a cavity or crater-like sore. Ulcers are commonly associated with conditions such as peptic ulcer disease, where the lining of the stomach or duodenum is eroded, or with pressure ulcers, which develop due to prolonged pressure on the skin. In the context of acute inflammation, the ulcer represents a severe reaction where the body’s response to injury or infection leads to the destruction of the epithelial surface.
Which cytokines are pro inflammatory and which are anti inflammatory
Cytokines are signaling molecules produced by various cells in the body, including immune cells, that play critical roles in regulating the immune response.
Pro-inflammatory cytokines include:
1. Tumor necrosis factor-alpha (TNF-alpha)
2. Interleukin-1 (IL-1)
3. Interleukin-6 (IL-6)
4. Interleukin-8 (IL-8)
5. Interleukin-12 (IL-12)
6. Interferon-gamma (IFN-gamma)
7. IL 4 and IL 6 can be both pro and anti
These cytokines promote inflammation by increasing vascular permeability, recruiting immune cells to the site of infection or injury, and activating immune cells to eliminate pathogens.
Anti-inflammatory cytokines include:
1. Interleukin-10 (IL-10)
2. Transforming growth factor-beta (TGF-beta)
These cytokines help to dampen the immune response and resolve inflammation by inhibiting the production of pro-inflammatory cytokines, promoting tissue repair, and suppressing immune cell activation.
Balanced regulation between pro-inflammatory and anti-inflammatory cytokines is crucial for an effective immune response while minimizing tissue damage. Dysregulation of cytokine production can lead to chronic inflammation and autoimmune diseases.
State the the principal cytokines involved in acute and chronic inflammation,their sources and actions
State three acute phase proteins produced by the liver
What is ESR?
Here is the information you’ve provided about:
-
TNF (Tumor Necrosis Factor)
- Principal Sources: Macrophages, mast cells, T lymphocytes
-
Principal Actions:
- Stimulates the expression of endothelial adhesion molecules.
- Induces the secretion of other cytokines.
- Has systemic effects, including fever and the acute phase response.
-
IL-1 (Interleukin-1)
- Principal Sources: Macrophages, endothelial cells, some epithelial cells
-
Principal Actions:
- Similar to TNF, with a role in the expression of adhesion molecules and cytokine secretion.
- Plays a greater role in inducing fever compared to TNF.
-
IL-6 (Interleukin-6)
- Principal Sources: Macrophages, other cells
-
Principal Actions:
- Mediates systemic effects, especially the acute phase response, which includes the production of acute-phase proteins by the liver.
-
Chemokines
- Principal Sources: Macrophages, endothelial cells, T lymphocytes, mast cells, other cell types
-
Principal Actions:
- Recruitment of leukocytes (such as neutrophils and monocytes) to sites of inflammation.
- Regulate the migration of cells in normal tissues during homeostasis.
-
IL-17 (Interleukin-17)
- Principal Sources: T lymphocytes
-
Principal Actions:
- Promotes the recruitment of neutrophils and monocytes to sites of acute inflammation.
-
IL-12 (Interleukin-12)
- Principal Sources: Dendritic cells, macrophages
-
Principal Actions:
- Stimulates increased production of IFN-γ (Interferon-gamma), a key cytokine in chronic inflammation.
-
IFN-γ (Interferon-gamma)
- Principal Sources: T lymphocytes, NK (Natural Killer) cells
-
Principal Actions:
- Activates macrophages, enhancing their ability to kill microbes and tumor cells.
- Plays a critical role in the immune response to intracellular pathogens.
-
IL-17 (Interleukin-17)
- Principal Sources: T lymphocytes
-
Principal Actions:
- Similar to its role in acute inflammation, IL-17 recruits neutrophils and monocytes to sites of chronic inflammation as well.
These cytokines are key mediators in the inflammatory response, with specific roles in either acute or chronic inflammation, contributing to various physiological and pathological processes.
Cytokine
Principal Sources
Principal Actions in Inflammation
In Acute Inflammation
TNF
Macrophages, mast cells, T lymphocytes
Stimulates expression of endothelial adhesion molecules and secretion of other cytokines; systemic effects
IL-I
Macrophages, endothelial cells, some epithelial cells
Similar to TNF; greater role in fever
IL-6
Macrophages, other cells
Systemic effects (acute phase response)
Chemokines
Macrophages, endothelial cells, T lymphocytes, mast cells, other cell types
Recruitment of leukocytes to sites of inflammation; migration of cells in normal tissues
IL-17
T lymphocytes
Recruitment of neutrophils and monocytes
In Chronic Inflammation
IL-12
Dendritic cells, macrophages
Increased production of IFN-y
IFN-Y
T lymphocytes, NK cells
Activation of macrophages (increased ability to kill microbes and tumor cells
IL-17
T lymphocytes
Recruitment of neutrophils and monocytes
Here is a list of key acute-phase liver proteins:
- C-Reactive Protein (CRP)
- Serum Amyloid A (SAA)
- Fibrinogen
- Haptoglobin
- Complement Proteins (C3, C4)
- Alpha-1 Antitrypsin
- Ferritin
- Ceruloplasmin
- Albumin
- Transferrin
Erythrocyte Sedimentation Rate (ESR) is not an acute-phase protein itself. However, it is a test that indirectly measures the presence of acute-phase proteins in the blood and the degree of inflammation in the body.
What ESR Measures:
• ESR is the rate at which red blood cells (erythrocytes) settle at the bottom of a test tube over a specific period (usually one hour). • Inflammation can cause an increase in certain acute-phase proteins, such as fibrinogen. These proteins cause red blood cells to stick together and form clumps, which settle faster than individual cells.
ESR and Acute-Phase Proteins:
• During inflammation, the concentration of acute-phase proteins increases in the blood. • The elevated levels of these proteins, especially fibrinogen, increase the ESR.
Which cytokines exhibit systemic effects in the heart,endothelial cells,blood vessels,skeletal muscles and multiple tissues
TNF
Which cytokines exhibit systemic protective effects in the brain,liver and bone marrow
Brain:TNF IL-1 IL-6
Liver: IL-1 IL-6
Bone marrow: TNF IL-1 IL-6
Here are the MCQs without the answers:
1. Nissl Bodies
Which of the following best describes Nissl bodies?
A. Iron-containing granules found in red blood cells
B. Protein aggregates found in neurons involved in protein synthesis
C. Eosinophilic inclusions seen in hepatocytes
D. Apoptotic bodies found in viral hepatitis
2. Negri Bodies
Negri bodies are most commonly associated with which disease?
A. Alzheimer’s disease
B. Rabies
C. Tuberculosis
D. Parkinson’s disease
3. Psammoma Bodies
Psammoma bodies are typically found in which of the following conditions?
A. Cirrhosis of the liver
B. Rabies infection
C. Papillary thyroid carcinoma
D. Sarcoidosis
4. Russell Bodies
Russell bodies, which contain immunoglobulins, are commonly seen in:
A. Multiple myeloma
B. Rabies infection
C. Rheumatic fever
D. Tuberculosis
5. Mallory Bodies (Mallory-Denk Bodies)
Mallory bodies are most characteristic of which disease?
A. Alzheimer’s disease
B. Alcoholic liver disease
C. Tuberculosis
D. Parkinson’s disease
6. Councilman Bodies
Councilman bodies, representing dying hepatocytes, are seen in:
A. Hepatitis and yellow fever
B. Parkinson’s disease
C. Multiple myeloma
D. Rheumatic fever
7. Aschoff Bodies
Aschoff bodies are characteristic of which condition?
A. Rheumatic fever
B. Tuberculosis
C. Alzheimer’s disease
D. Hemochromatosis
8. Hyaline Bodies
Hyaline bodies are typically associated with:
A. Cirrhosis and renal disease
B. Parkinson’s disease
C. Rabies infection
D. Multiple myeloma
9. Michaelis-Gutmann Bodies
Michaelis-Gutmann bodies are most commonly seen in:
A. Parkinson’s disease
B. Rabies infection
C. Malakoplakia
D. Alcoholic liver disease
10. Hemosiderin Bodies
Hemosiderin bodies are most commonly associated with:
A. Iron overload or chronic hemorrhage
B. Rheumatic fever
C. Tuberculosis
D. Viral hepatitis
11. Zenker’s Bodies (Zenker’s Necrosis)
Zenker’s necrosis is typically associated with:
A. Skeletal muscle injury
B. Hepatic necrosis
C. Iron overload
D. Plasma cell neoplasms
12. Lewy Bodies
Lewy bodies are pathological inclusions seen in:
A. Alzheimer’s disease
B. Parkinson’s disease
C. Rabies infection
D. Rheumatic fever
13. Dutcher Bodies
Dutcher bodies are intranuclear inclusions found in which condition?
A. Parkinson’s disease
B. Waldenström’s macroglobulinemia
C. Rheumatic fever
D. Malakoplakia
14. Schaumann Bodies
Schaumann bodies are found in which granulomatous disease?
A. Sarcoidosis
B. Multiple myeloma
C. Tuberculosis
D. Rheumatic fever
15. Pappenheimer Bodies
Pappenheimer bodies are inclusions found in red blood cells and are commonly seen in:
A. Parkinson’s disease
B. Sideroblastic anemia
C. Rabies infection
D. Sarcoidosis
Here are multiple-choice questions (MCQs) based on each type of body listed in pathology:
1. Nissl Bodies
Which of the following best describes Nissl bodies?
A. Iron-containing granules found in red blood cells
B. Protein aggregates found in neurons involved in protein synthesis
C. Eosinophilic inclusions seen in hepatocytes
D. Apoptotic bodies found in viral hepatitis
Answer: B
2. Negri Bodies
Negri bodies are most commonly associated with which disease?
A. Alzheimer’s disease
B. Rabies
C. Tuberculosis
D. Parkinson’s disease
Answer: B
Negri bodies are eosinophilic inclusion bodies formed in the cytoplasm of rabies virus-infected neurons.
3. Psammoma Bodies
Psammoma bodies are typically found in which of the following conditions?
A. Cirrhosis of the liver
B. Rabies infection
C. Papillary thyroid carcinoma
D. Sarcoidosis
Answer: C
4. Russell Bodies
Russell bodies, which contain immunoglobulins, are commonly seen in:
A. Multiple myeloma
B. Rabies infection
C. Rheumatic fever
D. Tuberculosis
Answer: A
5. Mallory Bodies (Mallory-Denk Bodies)
Mallory bodies are most characteristic of which disease?
A. Alzheimer’s disease
B. Alcoholic liver disease
C. Tuberculosis
D. Parkinson’s disease
Answer: B
6. Councilman Bodies
Councilman bodies, representing dying hepatocytes, are seen in:
A. Hepatitis and yellow fever
B. Parkinson’s disease
C. Multiple myeloma
D. Rheumatic fever
Answer: A
7. Aschoff Bodies
Aschoff bodies are characteristic of which condition?
A. Rheumatic fever
B. Tuberculosis
C. Alzheimer’s disease
D. Hemochromatosis
Answer: A
8. Hyaline Bodies
Hyaline bodies are typically associated with:
A. Cirrhosis and renal disease
B. Parkinson’s disease
C. Rabies infection
D. Multiple myeloma
Answer: A
9. Michaelis-Gutmann Bodies
Michaelis-Gutmann bodies are most commonly seen in:
A. Parkinson’s disease
B. Rabies infection
C. Malakoplakia
D. Alcoholic liver disease
Answer: C
10. Hemosiderin Bodies
Hemosiderin bodies are most commonly associated with:
A. Iron overload or chronic hemorrhage
B. Rheumatic fever
C. Tuberculosis
D. Viral hepatitis
Answer: A
11. Zenker’s Bodies (Zenker’s Necrosis)
Zenker’s necrosis is typically associated with:
A. Skeletal muscle injury
B. Hepatic necrosis
C. Iron overload
D. Plasma cell neoplasms
Answer: A
12. Lewy Bodies
Lewy bodies are pathological inclusions seen in:
A. Alzheimer’s disease
B. Parkinson’s disease
C. Rabies infection
D. Rheumatic fever
Answer: B
13. Dutcher Bodies
Dutcher bodies are intranuclear inclusions found in which condition?
A. Parkinson’s disease
B. Waldenström’s macroglobulinemia
C. Rheumatic fever
D. Malakoplakia
Answer: B
14. Schaumann Bodies
Schaumann bodies are found in which granulomatous disease?
A. Sarcoidosis
B. Multiple myeloma
C. Tuberculosis
D. Rheumatic fever
Answer: A
15. Pappenheimer Bodies
Pappenheimer bodies are inclusions found in red blood cells and are commonly seen in:
A. Parkinson’s disease
B. Sideroblastic anemia
C. Rabies infection
D. Sarcoidosis
Answer: B
—Pappenheimer bodies are abnormal basophilic granules of iron found inside red blood cells
Pappenheimer bodies are abnormal, iron-containing granules that appear within red blood cells (RBCs). They are composed of iron that is not properly incorporated into hemoglobin and are typically seen in conditions where iron metabolism or red blood cell production is disturbed.
Pappenheimer bodies can be identified using special stains, such as Prussian blue stain, which highlights the iron content.
These questions cover the pathology of each type of body and the diseases they are associated with, helping reinforce their diagnostic significance.
Type IV hypersensitivity is closely associated with chronic inflammation in French involves macrophages and T cells
Bradykinin is mainly responsible for pain.
Granulation tissue made up of new capillaries and fibroblasts is a hallmark of chronic inflammation and wound healing
Complement 3b is invovled in opsonization which enhances phagocytosis
What is a chemotactic factor for neutrophils?
• a) IL-4
• b) Complement C5a
• c) Histamine
• d) Serotonin
Answer: b) Complement C5a
Explanation: Complement C5a acts as a potent chemotactic factor for neutrophils, guiding them to the site of infection or injury.
Hypersensitivity reactions are exaggerated immune responses that cause tissue damage. They are classified into four types:
- Type I Hypersensitivity (Immediate): This involves IgE antibodies and occurs quickly after exposure to an allergen (e.g., pollen, food). It causes allergic reactions such as asthma, hay fever, and anaphylaxis. Mast cells and basophils release histamine and other mediators, leading to symptoms like itching, swelling, and bronchoconstriction.
- Type II Hypersensitivity (Cytotoxic): This involves IgG or IgM antibodies targeting antigens on cell surfaces, leading to cell destruction via complement activation or antibody-dependent cellular cytotoxicity (ADCC). Examples include hemolytic anemia and Rh incompatibility in newborns.
- Type III Hypersensitivity (Immune Complex): Immune complexes (antigen-antibody complexes) form and deposit in tissues, causing inflammation and tissue damage. This is seen in conditions like systemic lupus erythematosus (SLE) and post-streptococcal glomerulonephritis.
- Type IV Hypersensitivity (Delayed-type): This is cell-mediated, involving T-cells rather than antibodies. It takes 48–72 hours to develop. Common examples include contact dermatitis (poison ivy) and the tuberculin skin test. Chronic inflammation can also be part of this response.
Prostaglandins are lipid mediators produced at the site of inflammation. They play several key roles:
- Induce vasodilation, increasing blood flow to the inflamed area, contributing to redness and heat.
- Promote pain by sensitizing nerve endings, contributing to the perception of pain (hyperalgesia).
- Mediate fever by acting on the hypothalamus to raise body temperature.
- Prostaglandins also contribute to the inflammatory response by enhancing the permeability of blood vessels.
In the context of inflammation, prostaglandins work alongside other mediators like histamine and bradykinin to intensify the response.
The question asks, “Which phase of acute inflammation is characterized by exudate formation?”
- a) Initiation phase: This is the early stage of inflammation where the injury is recognized, and chemical signals like histamine and cytokines are released. It involves vasodilation and changes in vascular permeability but does not directly result in exudate formation.
- b) Amplification phase: This is the correct answer. During this phase, the inflammatory response is amplified as more mediators (like prostaglandins, histamine, and cytokines) are released, causing increased vascular permeability. This allows fluid and immune cells (exudate) to leak into tissues, contributing to swelling and other symptoms of inflammation.
- c) Resolution phase: This phase involves the cessation of the inflammatory response and the repair of damaged tissues. Exudate formation would have already occurred by this point, and the focus is now on tissue healing.
- d) Edema phase: This is not a recognized phase of inflammation. While edema (swelling due to fluid accumulation) occurs during inflammation, it’s not a specific phase.
Serotonin (5-HT) is a mediator released primarily by platelets during inflammation. Its roles include:
- Vasoconstriction: Serotonin can cause blood vessel constriction in certain areas, regulating blood flow during the inflammatory process.
- Increased vascular permeability: Similar to histamine, serotonin can enhance the permeability of blood vessels, allowing immune cells and proteins to enter the site of inflammation.
- Pain mediation: Serotonin can also contribute to the sensation of pain during inflammation.
Overall, serotonin’s effects complement those of histamine and other mediators to coordinate the inflammatory response.
Which enzyme is responsible for the production of reactive oxygen species during inflammation?
• a) Nitric oxide synthase • b) NADPH oxidase • c) Cyclooxygenase • d) Lipoxygenase Answer: b) NADPH oxidase Explanation: NADPH oxidase generates reactive oxygen species (ROS) in phagocytes during the respiratory burst, a key mechanism in microbial killing during inflammation.
uestion 3: Which phase of acute inflammation involves the migration of leukocytes to the site of injury?
• a) Resolution: This is the phase where inflammation subsides and tissue repair begins. It comes after the cellular and vascular phases. • b) Vascular phase: In the vascular phase, changes in blood vessels occur, including vasodilation and increased permeability, leading to the movement of fluid and proteins into the injured tissue. • c) Cellular phase: This is the correct answer. The cellular phase involves the movement (migration) of leukocytes (mainly neutrophils) from the blood vessels to the site of injury or infection. • d) Tissue repair phase: This phase involves healing and the regeneration or replacement of damaged tissue. It comes after the inflammatory phase, focusing on repair.
Explanation of the Cellular Phase
The cellular phase of acute inflammation involves:
1. Margination: This is the process where leukocytes (white blood cells) move to the periphery of the blood vessel as blood flow slows down. 2. Rolling: The leukocytes “roll” along the vessel wall, mediated by selectins, weakly interacting with endothelial cells. 3. Adhesion: Leukocytes firmly adhere to the endothelium via integrins. 4. Transmigration (Diapedesis): The leukocytes move through the endothelial gaps to reach the site of injury. 5. Chemotaxis: Once out of the vessel, leukocytes follow chemical signals (chemoattractants) to move toward the area of damage or infection.
Key Terms in Inflammation:
• Margination: The process by which white blood cells move to the edges of blood vessels during inflammation. • Rolling: The weak, transient attachment of leukocytes to the endothelium, causing them to roll along the vessel walls. • Adhesion: The firm binding of leukocytes to endothelial cells, facilitated by integrins and selectins. • Transmigration (Diapedesis): The process where leukocytes squeeze through endothelial gaps to enter the tissue. • Chemotaxis: The movement of leukocytes toward the site of injury or infection, following a gradient of chemotactic signals (like cytokines or bacterial products).
Question 11: Why isn’t the answer Chemotaxis?
The question asks for the term describing the movement of leukocytes out of the circulatory system and toward the tissue.
• Chemotaxis refers to the movement of leukocytes within the tissue towards the site of injury or infection, following chemical signals. • The process of Diapedesis specifically refers to the act of white blood cells squeezing through the endothelium to exit the bloodstream, so it’s more appropriate for describing the actual crossing of the vessel wall
Question 12: Which type of inflammatory exudate is characterized by high levels of protein and the presence of fibrin?
1. a) Serous exudate: This is a thin, watery exudate with low protein content. It’s usually seen in mild inflammation, like in blisters or burns. 2. b) Fibrinous exudate: This is the correct answer. Fibrinous exudate contains high amounts of fibrin (a protein involved in clot formation). It occurs in more severe inflammatory conditions, such as in pericarditis, where the exudate can lead to the formation of fibrin deposits. 3. c) Purulent exudate: Purulent exudate is pus-filled, containing dead neutrophils, bacteria, and cell debris. It indicates a bacterial infection and is typically seen in abscesses or suppurative (pus-producing) infections. 4. d) Hemorrhagic exudate: This exudate contains red blood cells, indicating damage to blood vessels, and is seen in severe injuries or infections.
Chemical Phase of Inflammation:
The chemical phase involves the release of chemical mediators (such as histamine, serotonin, bradykinin, prostaglandins, cytokines, etc.) that regulate vascular and cellular responses during inflammation. These mediators orchestrate processes like:
1. Vasodilation: Mediators like histamine and prostaglandins increase blood flow to the site of injury, causing redness and heat. 2. Increased vascular permeability: Mediators like bradykinin and histamine increase the permeability of blood vessels, allowing proteins and immune cells to exit into the tissue. 3. Leukocyte recruitment: Chemical mediators such as cytokines and chemokines attract leukocytes (white blood cells) to the site of infection or injury, which is part of the cellular phase.
Phase Involved in the Accumulation of White Blood Cells (WBCs):
• Vascular phase: This phase involves changes in blood vessels like vasodilation and increased permeability but does not directly involve white blood cell accumulation. • Cellular phase: The cellular phase is where leukocyte accumulation (margination) occurs. As blood flow slows, white blood cells accumulate near the edges of the blood vessel (margination) before they adhere to the endothelium (rolling and adhesion) and then move out through the vessel wall (transmigration/diapedesis) to the site of injury. Accumulation of WBCs in the blood vessels happens in this phase.
To summarize, the cellular phase is responsible for the accumulation of WBCs before they move out of the bloodstream to the site of infection or injury.
Serotonin and Inflammation:
Regarding serotonin, although it is mainly known for its role as a neurotransmitter, in inflammation, serotonin is released by platelets and can cause vasoconstriction. It is more commonly involved in the initial response to vascular injury, helping to regulate blood flow at the site.
ou’re absolutely right that laminar flow plays a significant role in margination. Let me explain how margination and rolling happen in the context of inflammation and then I’ll provide you with MCQs on the vascular phase of inflammation.
Laminar Flow and Margination
In normal, non-inflamed vessels, blood flow is laminar, meaning the faster flow is in the center of the vessel, while slower flow is near the vessel walls. Red blood cells tend to stay in the center, while white blood cells (leukocytes) move closer to the vessel walls.
During inflammation, laminar blood flow slows down due to vasodilation (widening of the blood vessels). This slowing of blood flow helps push the leukocytes to the periphery of the vessel, a process called margination. This sets the stage for rolling, where the leukocytes weakly interact with the endothelial cells lining the blood vessels.
Rolling and Selectins vs Integrins
• Rolling occurs when selectins, which are adhesion molecules expressed on endothelial cells, form weak, transient bonds with carbohydrates (sialyl-Lewis X) on the leukocyte surface. These interactions cause the leukocytes to “roll” along the endothelial surface. • As leukocytes roll, integrins on their surface are activated by chemokines produced in the inflamed tissue. Once activated, integrins bind firmly to ICAM (Intercellular Adhesion Molecule) on the endothelial cells, leading to firm adhesion.
Selectins vs. Integrins:
• Selectins are primarily involved in the rolling phase, creating weak, transient interactions with leukocytes. • Integrins are primarily responsible for firm adhesion, securing the leukocytes to the endothelium before transmigration through the vessel wall.
Margination: Movement of white blood cells toward the edge of the blood vessel during inflammation.
• Rolling: Weak interaction between white blood cells and endothelial cells, mediated by selectins.
• Firm adhesion: Strong interaction between white blood cells and the endothelial cells, mediated by integrins.
• Transmigration (Diapedesis): Movement of white blood cells through the endothelial cell junctions to the site of inflammation.
C3a is classified as an anaphylatoxin, meaning it can trigger the rapid release of inflammatory mediators like histamine from mast cells and basophils. C3a promotes an increase in vascular permeability, C3a, like histamine and bradykinin, can trigger the dilation of blood vessels (vasodilation).
