Case Study 1 - Acute Inflammation Flashcards
A 62 year old woman was diagnosed with heart failure 3 years ago after a recent myocardial infarction. Since then she has been suffering with swelling of her legs. It gets worse towards the end of the day. Over the last 2 days, she has noticed that her lower legs are feeling very warm and looking red. She decides to go to her doctor to see what is wrong. (1)
What do you think has happened to the patient’s legs?
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A 62 year old woman was diagnosed with heart failure 3 years ago after a recent myocardial infarction. Since the she has been suffering with swelling of her legs. It gets worse towards the end of the day. Over the last 2 days, she has noticed that her lower legs are feeling very warm and looking red. She decides to go to her doctor to see what is wrong.
What are the clinical effects of acute inflammation?
Redness (rubor): due to increased blood flow & dilation of blood vessels in response to inflammation caused by release of inflammatory mediators that cause blood vessels to widen
Heat (calor): due to increased blood flow & metabolic activity in the area
Swelling (tumor): accumulation of fluid & white blood cells in the affected tissue (oedema), & is a result of increased vascular permeability
Pain (dolor): activation of pain receptors in the affected tissue caused by release of inflammatory chemicals such as prostaglandins which contributes to this sensation
Loss of function (functio laesa): impairs normal function of affected area, e.g. inflammation in a joint can restrict its range of motion
Fever: Systemic inflammation can lead to the release of certain chemicals, called pyrogens, which act on the hypothalamus in the brain, causing an increase in body temperature and fever.
Increased vascular dilation: During inflammation, blood vessels in the affected area dilate to allow more blood to flow to the site. This increased blood flow is part of the body’s defense mechanism to deliver immune cells and nutrients to the site of injury or infection.
Increased vascular permeability: Inflammation causes changes in the blood vessel walls, making them more permeable. This allows fluid, proteins, and immune cells to move from the bloodstream into the surrounding tissue, contributing to swelling and the formation of exudate (fluid containing immune cells and debris).
Migration of neutrophils: Neutrophils are a type of white blood cell that plays a crucial role in the early stages of acute inflammation. They are attracted to the site of inflammation by various chemical signals and help combat invading microorganisms.
A 62 year old woman was diagnosed with heart failure 3 years ago after a recent myocardial infarction. Since the she has been suffering with swelling of her legs. It gets worse towards the end of the day. Over the last 2 days, she has noticed that her lower legs are feeling very warm and looking red. She decides to go to her doctor to see what is wrong.
List some causes of acute inflammation. What do you think the cause could be in this case?
infection, trauma, allergic reactions, ischemia (inadequate blood supply), exposure to chemical irritants, toxins. In this case, the cause could be an infection
A 62 year old woman was diagnosed with heart failure 3 years ago after a recent myocardial infarction. Since the she has been suffering with swelling of her legs. It gets worse towards the end of the day. Over the last 2 days, she has noticed that her lower legs are feeling very warm and looking red. She decides to go to her doctor to see what is wrong.
The doctor examines the patient’s legs. They appear swollen and there is ‘pitting oedema.’ They are very warm to touch, and the patient tells him that they are very painful and stopping her from sleeping. The GP decides to take a biopsy and sends it to the pathologist.
Look at the picture showing normal skin histology. Label the structures in the
picture. (2)
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A 62 year old woman was diagnosed with heart failure 3 years ago after a recent myocardial infarction. Since the she has been suffering with swelling of her legs. It gets worse towards the end of the day. Over the last 2 days, she has noticed that her lower legs are feeling very warm and looking red. She decides to go to her doctor to see what is wrong.
The doctor examines the patient’s legs. They appear swollen and there is ‘pitting oedema.’ They are very warm to touch, and the patient tells him that they are very painful and stopping her from sleeping. The GP decides to take a biopsy and sends it to the pathologist.
The following picture shows part of the biopsy from our patient. Describe what
you can see. (3)
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A 62 year old woman was diagnosed with heart failure 3 years ago after a recent myocardial infarction. Since the she has been suffering with swelling of her legs. It gets worse towards the end of the day. Over the last 2 days, she has noticed that her lower legs are feeling very warm and looking red. She decides to go to her doctor to see what is wrong.
The doctor examines the patient’s legs. They appear swollen and there is ‘pitting oedema.’ They are very warm to touch, and the patient tells him that they are very painful and stopping her from sleeping. The GP decides to take a biopsy and sends it to the pathologist.
What is the characteristic cell type in acute inflammation? What do they do?
Neutrophils. They are part of the body’s innate immune system and play a crucial role in the initial response to tissue injury or infection. Here’s what they do during acute inflammation:
Phagocytosis: Neutrophils are highly specialized in engulfing and destroying foreign particles, such as bacteria, fungi, and cellular debris, through a process called phagocytosis. They have receptors on their surfaces that recognize and bind to pathogens, marking them for destruction.
Release of inflammatory mediators: When neutrophils encounter pathogens or inflammatory stimuli, they release various inflammatory mediators, including chemokines and cytokines. Chemokines are particularly important because they act as signaling molecules that attract other immune cells to the site of inflammation, promoting an immune response.
Chemotaxis: Neutrophils are capable of sensing and following chemical gradients, which allows them to migrate toward the site of inflammation or infection. This directed movement is known as chemotaxis and is guided by chemokines released by damaged tissues or other immune cells.
Neutrophil extracellular traps (NETs): In addition to phagocytosis, neutrophils can release a specialized defense mechanism known as neutrophil extracellular traps (NETs). NETs are composed of chromatin (DNA) and cytoplasmic proteins that form a mesh-like structure to trap and immobilize pathogens, such as bacteria and fungi. This immobilization helps prevent the spread of the pathogens and facilitates their destruction by other immune cells.
A 62 year old woman was diagnosed with heart failure 3 years ago after a recent myocardial infarction. Since the she has been suffering with swelling of her legs. It gets worse towards the end of the day. Over the last 2 days, she has noticed that her lower legs are feeling very warm and looking red. She decides to go to her doctor to see what is wrong.
The doctor examines the patient’s legs. They appear swollen and there is ‘pitting oedema.’ They are very warm to touch, and the patient tells him that they are very painful and stopping her from sleeping. The GP decides to take a biopsy and sends it to the pathologist.
What is your diagnosis?
Cellulitis. It is caused by bacterial infection e.g. streptococcus. It’s an infection of the lower extremities & it’s localised
A 62 year old woman was diagnosed with heart failure 3 years ago after a recent myocardial infarction. Since the she has been suffering with swelling of her legs. It gets worse towards the end of the day. Over the last 2 days, she has noticed that her lower legs are feeling very warm and looking red. She decides to go to her doctor to see what is wrong.
The doctor examines the patient’s legs. They appear swollen and there is ‘pitting oedema.’ They are very warm to touch, and the patient tells him that they are very painful and stopping her from sleeping. The GP decides to take a biopsy and sends it to the pathologist.
The GP takes a swab of the skin surface. The results are positive for a bacterial infection.
What would you prescribe for the patient?
Antibiotics which include penicillin derivatives such as amoxicillin or dicloxacillin, (or clindamycin: alternative to those allergic to penicillin), pain killers, diuretics to reduce peripheral oedema
A 62 year old woman was diagnosed with heart failure 3 years ago after a recent myocardial infarction. Since the she has been suffering with swelling of her legs. It gets worse towards the end of the day. Over the last 2 days, she has noticed that her lower legs are feeling very warm and looking red. She decides to go to her doctor to see what is wrong.
The doctor examines the patient’s legs. They appear swollen and there is ‘pitting oedema.’ They are very warm to touch, and the patient tells him that they are very painful and stopping her from sleeping. The GP decides to take a biopsy and sends it to the pathologist.
The GP takes a swab of the skin surface. The results are positive for a bacterial infection.
What is the difference between COX 1 and COX 2 inhibitors? What is this significance for the patient?
COX (cyclooxygenase) inhibitors are a class of drugs that work by blocking the action of the COX enzymes. These enzymes convert arachidonic acid, a type of fatty acid into prostaglandins and are therefore responsible for the synthesis of prostaglandins, and other pro-inflammatory mediators. There are two main isoforms of the COX enzyme: COX-1 and COX-2. Here’s the difference between COX-1 and COX-2 inhibitors and their significance for patients:
COX-1 Inhibitors:
COX-1 is constitutively expressed in various tissues throughout the body, including the gastrointestinal (GI) tract, platelets, and kidneys.
In the GI tract, COX-1 plays a crucial role in maintaining the protective mucosal lining, promoting mucus and bicarbonate production, and regulating blood flow.
COX-1 inhibitors can disrupt the protective effects of prostaglandins in the GI tract, leading to a higher risk of adverse effects like gastric ulcers, stomach bleeding, and other GI complications. This is because prostaglandins produced by COX-1 help protect the stomach lining from the harsh acidic environment.
Examples of COX-1 inhibitors include traditional nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, and diclofenac.
COX-2 Inhibitors:
COX-2 is an inducible enzyme that is primarily expressed at sites of inflammation and in response to injury or immune activation.
COX-2 plays a key role in generating prostaglandins that promote inflammation, pain, and fever.
COX-2 inhibitors selectively target the COX-2 enzyme while sparing COX-1, which helps reduce the risk of GI side effects, such as bleeding and ulceration.
COX-2 inhibitors are often used to manage pain and inflammation associated with conditions like osteoarthritis and rheumatoid arthritis.
Examples of COX-2 inhibitors include celecoxib, rofecoxib (withdrawn from the market due to safety concerns), and etoricoxib.
Significance for Patients:
The significance of COX-1 and COX-2 inhibitors lies in their different safety profiles, particularly regarding GI side effects. COX-1 inhibitors can cause GI complications due to their effects on the stomach lining, making them less desirable for patients at risk of GI bleeding or with a history of ulcers. On the other hand, COX-2 inhibitors are considered safer in terms of GI tolerability because they selectively target the COX-2 enzyme, sparing COX-1 and preserving the protective mechanisms in the GI tract.
However, it’s essential to note that COX-2 inhibitors have been associated with an increased risk of cardiovascular events in some patients. Therefore, the choice of COX inhibitor should be carefully considered by the healthcare provider, taking into account the patient’s medical history and individual risk factors. Additionally, it is crucial for patients to use these medications as prescribed and to be aware of potential side effects and interactions with other drugs.
A 62 year old woman was diagnosed with heart failure 3 years ago after a recent myocardial infarction. Since the she has been suffering with swelling of her legs. It gets worse towards the end of the day. Over the last 2 days, she has noticed that her lower legs are feeling very warm and looking red. She decides to go to her doctor to see what is wrong.
The doctor examines the patient’s legs. They appear swollen and there is ‘pitting oedema.’ They are very warm to touch, and the patient tells him that they are very painful and stopping her from sleeping. The GP decides to take a biopsy and sends it to the pathologist.
The GP takes a swab of the skin surface. The results are positive for a bacterial infection.
How does Benzylpenicillin work?
Benzylpenicillin, also known as penicillin G, is a beta-lactam antibiotic that belongs to the penicillin class of antibiotics. It works by targeting the bacterial cell wall, which is crucial for maintaining the structural integrity and shape of the bacteria. Bacterial cell walls are composed of peptidoglycan, a mesh-like structure made up of repeating units of sugar and amino acids.
The mechanism of action of benzylpenicillin involves interfering with the second stage of cell wall synthesis, which is the cross-linking of peptidoglycan chains. This process is facilitated by the enzyme transpeptidase (also known as penicillin-binding proteins or PBPs). Transpeptidase catalyzes the formation of peptide bonds between the amino acids in adjacent peptidoglycan chains, which results in a strong and rigid cell wall.
Benzylpenicillin, as a beta-lactam antibiotic, contains a beta-lactam ring in its chemical structure. When the antibiotic enters the bacterial cell, it binds to and inhibits the activity of transpeptidase (PBPs). By doing so, it prevents the cross-linking of peptidoglycan chains, leading to the weakening of the cell wall’s structural integrity. The cell wall becomes susceptible to osmotic pressure and eventually lyses (bursts) as the bacterium tries to divide or grow, resulting in bacterial cell death.
It’s important to note that benzylpenicillin primarily targets Gram-positive bacteria due to differences in their cell wall structures. Gram-negative bacteria have an additional outer membrane that restricts the access of some antibiotics, including benzylpenicillin, to their cell wall.
Benzylpenicillin is an effective antibiotic against a variety of Gram-positive bacteria, including Streptococcus, Staphylococcus, and some species of Neisseria. However, it has limited activity against Gram-negative bacteria and is susceptible to degradation by certain enzymes, such as beta-lactamases, produced by some bacteria. To combat bacterial resistance, various semisynthetic penicillins and other beta-lactam antibiotics have been developed to address a broader range of bacterial infections.
A 23 year old student who is normally fit and well, develops a generalised headache. His friends notice that he appears lethargic and doesn’t seem himself. He complains of a stiff neck and feels very hot. His friends are concerned and take him to A&E.
Can you explain why the student is experiencing these symptoms?
A headache can be caused by increased intracranial pressure. This is the pressure inside your skull, which can increase due to inflammation.
Stiff neck, on the other hand, can indeed be caused by irritation or inflammation of the meninges, the protective membranes that cover the brain and spinal cord. More specifically, the arachnoid and pia mater layers can become inflamed in conditions such as meningitis. The inflammation causes these layers to swell, leading to symptoms such as a stiff neck, headache, and sensitivity to light.
A 23 year old student who is normally fit and well, develops a generalised headache. His friends notice that he appears lethargic and doesn’t seem himself. He complains of a stiff neck and feels very hot. His friends are concerned and take him to A&E.
When he arrives at A&E, the junior doctor is very concerned by the history of this patient. He prescribes a dose of ceftriaxone immediately. What class of drug is this & how does it work?
Ceftriaxone is a third-generation cephalosporin antibiotic. The cephalosporins are a large group of antibiotics that are structurally related to the penicillins.
Ceftriaxone, like other cephalosporins, works by inhibiting the synthesis of the bacterial cell wall. It does this by binding to penicillin-binding proteins (PBPs), which are enzymes located on the inner membrane of the bacterial cell wall. PBPs are involved in the final stages of assembling the bacterial cell wall, specifically in the cross-linking of the peptidoglycan (the main structural component of the cell wall) chains.
By binding to these proteins, ceftriaxone disrupts the process of cell wall synthesis, which weakens the wall and makes the bacterial cell susceptible to osmotic lysis (breaking down due to an imbalance in pressure). This results in the death of the bacteria, thereby helping to clear the infection.
A 23 year old student who is normally fit and well, develops a generalised headache. His friends notice that he appears lethargic and doesn’t seem himself. He complains of a stiff neck and feels very hot. His friends are concerned and take him to A&E.
What do you think is wrong with our patient? What are the causes of this condition?
Meningitis. Its causes include bacterial infections such as Neisseria meningitidis & pneumococcus,
viral infections such as enterovirus, herpes simplex virus,
fungi, protozoa
A 23 year old student who is normally fit and well, develops a generalised headache. His friends notice that he appears lethargic and doesn’t seem himself. He complains of a stiff neck and feels very hot. His friends are concerned and take him to A&E.
The junior doctor also prescribes some Dexamethasone. What is it & how does it work?
Dexamethasone is a type of corticosteroid medication, specifically, it’s a glucocorticoid. Glucocorticoids are a class of corticosteroids that are involved in a range of physiological processes including the regulation of inflammatory responses.
Dexamethasone works by mimicking the action of cortisol, a hormone that your body naturally produces in the adrenal glands. This hormone and, by extension, dexamethasone, have potent anti-inflammatory and immunosuppressive properties.
When dexamethasone enters a cell, it binds to the glucocorticoid receptor that’s found in the cytoplasm. The drug-receptor complex then moves into the cell nucleus where it binds to specific parts of the DNA, leading to changes in gene transcription. This results in a decrease in the production of proteins that promote inflammation and an increase in the production of proteins that inhibit inflammation.
In the context of reducing inflammation in the meninges to lower intracranial pressure, dexamethasone can reduce swelling and inflammation caused by diseases like meningitis. This can alleviate symptoms like headaches and a stiff neck.
A 23 year old student who is normally fit and well, develops a generalised headache. His friends notice that he appears lethargic and doesn’t seem himself. He complains of a stiff neck and feels very hot. His friends are concerned and take him to A&E.
What are the complications of his condition?
brain damage, seizures, hearing loss, vision problems, cognitive impairment
