Case Study 1 - Acute Inflammation Flashcards

1
Q

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?

A

Image

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2
Q

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?

A

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.

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3
Q

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?

A

infection, trauma, allergic reactions, ischemia (inadequate blood supply), exposure to chemical irritants, toxins. In this case, the cause could be an infection

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4
Q

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)

A

Image

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5
Q

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)

A

Image

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6
Q

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?

A

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.

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7
Q

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?

A

Cellulitis. It is caused by bacterial infection e.g. streptococcus. It’s an infection of the lower extremities & it’s localised

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8
Q

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?

A

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

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9
Q

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?

A

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.

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10
Q

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?

A

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.

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11
Q

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

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.

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12
Q

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?

A

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.

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13
Q

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?

A

Meningitis. Its causes include bacterial infections such as Neisseria meningitidis & pneumococcus,
viral infections such as enterovirus, herpes simplex virus,
fungi, protozoa

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14
Q

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?

A

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.

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15
Q

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?

A

brain damage, seizures, hearing loss, vision problems, cognitive impairment

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16
Q

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 does this picture show? (4)

A

Image

17
Q

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.

Why has the patient developed this? Explain the underlying pathogenic mechanisms. (4)

A

Your description accurately outlines one potential cause of a non-blanching rash, which can indeed be a sign of severe bacterial infection, such as meningococcal sepsis or meningitis, caused by Neisseria meningitidis.

The bacteria can produce toxins that lead to damage to the vascular endothelium, the cells lining the blood vessels. This can cause the vessels to leak, resulting in purpura (spots of blood under the skin) that do not disappear, or “blanch,” when pressure is applied to them. This is why such rashes are called non-blanching.

In addition some bacterial toxins can trigger disseminated intravascular coagulation (DIC), a serious condition where the blood begins to clot excessively throughout the body’s small blood vessels. This can lead to blockages that disrupt normal blood flow and organ function. At the same time, because the clotting factors and platelets are being consumed in these unnecessary clots, the patient becomes prone to severe bleeding, even from minor injuries. This is known as a consumptive coagulopathy.

18
Q

A 45 year old woman arrives at the Surgical Assessment Unit complaining of abdominal pain. She had just eaten fish and chips 2 hours previously and noticed the onset of the pain in the upper right quadrant of her abdomen. She also feels nauseous but has no bowel symptoms. The doctor notices that she is quite overweight, and is markedly tender on palpation of the right side of her abdomen.

What could be causing these symptoms?

A

Acute cholecystitis, appendicitis

19
Q

A 45 year old woman arrives at the Surgical Assessment Unit complaining of abdominal pain. She had just eaten fish and chips 2 hours previously and noticed the onset of the pain in the upper right quadrant of her abdomen. She also feels nauseous but has no bowel symptoms. The doctor notices that she is quite overweight, and is markedly tender on palpation of the right side of her abdomen.

The doctor orders some blood tests. Her white cell count and CRP are raised. What is CRP and does this help with your diagnosis?

A

C-reactive protein (CRP) is indeed a protein that is produced in the liver and rises in response to inflammation. It is used as a biomarker in medicine, and high levels of CRP in the blood can indicate inflammation due to various conditions, such as infection, trauma, autoimmune diseases, and others.

CRP is considered an inflammatory marker because its levels rise in response to inflammation in the body.

As you rightly noted, CRP is part of the body’s acute phase response to inflammation or infection. Interleukin-6 (IL-6) is one of the cytokines (signalling molecules of the immune system) that triggers the liver to produce and release more CRP into the bloodstream during this response.

CRP can bind to various substances, including the phospholipids found on the surface of dead or dying cells (apoptotic cells) and certain bacteria. Once bound, CRP can activate the body’s complement system, a part of the immune system that enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells from the body. It also promotes inflammation and attacks the pathogen’s cell membrane.

CRP acts as an opsonin, meaning it can coat the surface of these cells or bacteria, marking them for destruction and making it easier for white blood cells like macrophages and neutrophils to recognize and engulf them (a process known as phagocytosis).

By these mechanisms, CRP helps the body to manage inflammation, clear cellular debris and microbes, and restore homeostasis. But it’s important to remember that a high CRP level is a non-specific indicator of inflammation and isn’t diagnostic of any particular condition on its own. Other tests are typically needed to diagnose the specific cause of the inflammation.

20
Q

A 45 year old woman arrives at the Surgical Assessment Unit complaining of abdominal pain. She had just eaten fish and chips 2 hours previously and noticed the onset of the pain in the upper right quadrant of her abdomen. She also feels nauseous but has no bowel symptoms. The doctor notices that she is quite overweight, and is markedly tender on palpation of the right side of her abdomen.

The next day the patient goes for an ultrasound scan of her abdomen. What do you think was found?

A

Distended/swollen gallbladder with gallstones which may be due to accumulation of bile

21
Q

A 45 year old woman arrives at the Surgical Assessment Unit complaining of abdominal pain. She had just eaten fish and chips 2 hours previously and noticed the onset of the pain in the upper right quadrant of her abdomen. She also feels nauseous but has no bowel symptoms. The doctor notices that she is quite overweight, and is markedly tender on palpation of the right side of her abdomen.

How are gallstones formed and what the different types? Can you explain why our patient is experiencing the symptoms described?

A

Gallstones are hard particles that develop in your gallbladder, an organ located under your liver in the upper right part of your abdomen. The gallbladder’s primary job is to store bile, a substance that helps your body break down fatty foods.

There are two main types of gallstones:

Cholesterol gallstones: These are the most common type and are often yellow in color. They are formed when your liver makes more cholesterol than your bile can dissolve. When this happens, the extra cholesterol can start to form crystals, which can eventually become gallstones.

Pigment gallstones: These are darker and are formed when your gallbladder can’t break down a substance called bilirubin. Bilirubin is produced when your body breaks down red blood cells. Sometimes, due to certain medical conditions, your gallbladder may have trouble breaking down bilirubin, which can then combine with calcium and other substances to form stones.

Now, coming to your condition. The pain in the right upper part of your abdomen and nausea could be due to gallstones. When a gallstone blocks the ducts that bile uses to enter the small intestine, this can cause a sharp pain that you might feel in your upper right abdomen or in the centre of your stomach, below your breastbone. This pain might be especially noticeable shortly after you eat a meal, particularl y if the meal was high in fat.

Being overweight can increase the amount of cholesterol your liver produces, and that can raise your risk of developing cholesterol gallstones.

The tenderness the doctor noticed when pressing on your right abdomen might be due to inflammation caused by the gallstones blocking the bile ducts.

22
Q

A 45 year old woman arrives at the Surgical Assessment Unit complaining of abdominal pain. She had just eaten fish and chips 2 hours previously and noticed the onset of the pain in the upper right quadrant of her abdomen. She also feels nauseous but has no bowel symptoms. The doctor notices that she is quite overweight, and is markedly tender on palpation of the right side of her abdomen.

The patient is given some medications, 3 of which are tazocin, metronidazole and metoclopramide. Explain their reason for prescription, drug class, mechanism of action, administration, half-life, & excretion

A

Reason for prescription: Metronidazole is used to treat certain kinds of bacterial and parasitic infections. This includes infections in different parts of the body such as the skin, stomach, intestines, and the female reproductive system. It can also be used for the prevention of infection after surgery.

Drug Class: Metronidazole belongs to a class of drugs known as nitroimidazoles.

Mechanism of Action: The drug works by interfering with the DNA in bacteria and parasites. It’s able to enter the cells of these microorganisms, where it’s then converted into its active form. In this active form, metronidazole can disrupt the structure of the microorganism’s DNA, preventing it from producing essential proteins and leading to the death of the bacteria or parasite.

Administration: Metronidazole can be taken orally as a tablet or a liquid, used topically as a cream, gel, or lotion, or given by injection. The way it’s given depends on the type and location of the infection being treated.

Half-Life: The half-life of metronidazole varies, but in general, it’s around 8 hours in adults. This means that it takes around 8 hours for the body to reduce the amount of metronidazole in the bloodstream by half. The half-life can be affected by several factors, including the person’s age, kidney function, and liver function.

Excretion: Metronidazole is primarily excreted in the urine, but it can also be excreted in the feces to a lesser extent. Some of it is excreted in its original form, but some is also broken down by the liver into metabolites, which are then excreted.

Tazocin is a brand name for the combination antibiotic medication piperacillin/tazobactam. Here is the information you asked for:

Reason for prescription: Tazocin is used to treat a variety of bacterial infections. This includes infections of the skin, gynecological infections, abdominal infections, and respiratory tract infections among others. It is often used in hospitals for severe infections and infections caused by organisms that are resistant to other antibiotics.

Drug Class: Tazocin contains two different medications. Piperacillin is a broad-spectrum penicillin antibiotic, and tazobactam is a beta-lactamase inhibitor.

Mechanism of Action: Piperacillin works by interfering with the ability of bacteria to form cell walls, which they need to survive. Tazobactam enhances the effectiveness of piperacillin by inhibiting an enzyme (beta-lactamase) produced by some bacteria that can inactivate piperacillin and other penicillins. By blocking this enzyme, tazobactam allows piperacillin to work better and against a wider range of bacteria.

Administration: Tazocin is typically administered by intravenous (IV) injection or infusion, meaning it’s given directly into a vein.

Half-Life: The half-life of piperacillin and tazobactam is approximately 1 hour and 1.2 hours respectively. This means that it takes this amount of time for the concentration of each drug in the body to be reduced by half.

Excretion: Both piperacillin and tazobactam are primarily excreted unchanged by the kidneys into the urine. This means that people with impaired kidney function may require dosage adjustments, as the medication could be cleared more slowly from their bodies.

Metoclopramide is a medication that has several uses in the management of gastrointestinal conditions. Here is the information you asked for:

Reason for Prescription: Metoclopramide is primarily used to treat conditions like gastroesophageal reflux disease (GERD), gastroparesis (slow emptying of the stomach), and to prevent nausea and vomiting caused by surgery or chemotherapy.

Drug Class: Metoclopramide belongs to a class of drugs known as prokinetic agents. It also has antiemetic (anti-vomiting) properties.

Mechanism of Action: Metoclopramide works by blocking dopamine receptors in the brain, which can help to prevent nausea and vomiting. Its prokinetic effects are due to its ability to increase the muscle tone and peristalsis (muscular contractions) of the gastrointestinal tract, which can help to speed up the passage of food through the stomach.

Administration: Metoclopramide can be taken orally (as a tablet or liquid), or it can be given by injection into a muscle (intramuscular) or into a vein (intravenous).

Half-Life: The half-life of metoclopramide is approximately 5 to 6 hours. This means that it takes about this long for the amount of metoclopramide in the body to decrease by half.

Excretion: Metoclopramide is primarily excreted in the urine, and to a lesser extent in the feces. Approximately 85% of a dose is found in the urine within 72 hours.

23
Q

A 45 year old woman arrives at the Surgical Assessment Unit complaining of abdominal pain. She had just eaten fish and chips 2 hours previously and noticed the onset of the pain in the upper right quadrant of her abdomen. She also feels nauseous but has no bowel symptoms. The doctor notices that she is quite overweight, and is markedly tender on palpation of the right side of her abdomen.

What does half-life of a drug mean?

A

The term “half-life” refers to the time it takes for the amount of a substance, in this case a drug, to decrease by half in the body.

24
Q

A 45 year old woman arrives at the Surgical Assessment Unit complaining of abdominal pain. She had just eaten fish and chips 2 hours previously and noticed the onset of the pain in the upper right quadrant of her abdomen. She also feels nauseous but has no bowel symptoms. The doctor notices that she is quite overweight, and is markedly tender on palpation of the right side of her abdomen.

The patient is given analgesics, antiemetics, and antibiotics. She is discharged 5 days later. 2 weeks later she can’t resist going to McDonalds for her lunch. The pain returns and she has to go back to hospital. She is more unwell this time and her vital signs show her BP: 130/85, HR: 101, RR: 22, & Temp: 37.9

Can you give an explanation as to what has happened to our patient?

A

SIRS, or Systemic Inflammatory Response Syndrome, is an exaggerated defense response of the body to a variety of severe clinical insults. This response is manifested by two or more symptoms including fever or hypothermia, tachycardia (high heart rate), tachypnea (high respiratory rate), and change in blood leukocyte count.

Regarding the role of nitric oxide and endothelin-1:

Nitric Oxide (NO) is a potent vasodilator and helps to maintain blood vessel tone by preventing the vessel from constricting too much. It is produced within the blood vessels’ lining, the endothelium, and plays a key role in regulating vascular tone and blood flow.

Endothelin-1 is a potent vasoconstrictor, produced by endothelial cells. It’s usually kept in balance with vasodilators like nitric oxide. But in situations of inflammation or disease, this balance can be disturbed, leading to changes in vascular tone and blood flow.

In a state of systemic inflammation, such as SIRS, the production of pro-inflammatory cytokines like interleukin-1 and tumor necrosis factor-alpha can stimulate the production of large amounts of nitric oxide. This can result in widespread vasodilation, which can decrease systemic vascular resistance and lead to an increase in heart rate

25
Q

A 45 year old woman arrives at the Surgical Assessment Unit complaining of abdominal pain. She had just eaten fish and chips 2 hours previously and noticed the onset of the pain in the upper right quadrant of her abdomen. She also feels nauseous but has no bowel symptoms. The doctor notices that she is quite overweight, and is markedly tender on palpation of the right side of her abdomen.

The patient is given analgesics, antiemetics, and antibiotics. She is discharged 5 days later. 2 weeks later she can’t resist going to McDonalds for her lunch. The pain returns and she has to go back to hospital. She is more unwell this time and her vital signs show her BP: 130/85, HR: 101, RR: 22, & Temp: 37.9

After this episode is treated, the surgeons remove the patient’s gallbladder and the
pathologist looks at it under the microscope. What cell type can you see? Picture
A shows normal Gallbladder tissue, picture B is a close up of the cells (5)

A

Image

26
Q

A 45 year old woman arrives at the Surgical Assessment Unit complaining of abdominal pain. She had just eaten fish and chips 2 hours previously and noticed the onset of the pain in the upper right quadrant of her abdomen. She also feels nauseous but has no bowel symptoms. The doctor notices that she is quite overweight, and is markedly tender on palpation of the right side of her abdomen.

The patient is given analgesics, antiemetics, and antibiotics. She is discharged 5 days later. 2 weeks later she can’t resist going to McDonalds for her lunch. The pain returns and she has to go back to hospital. She is more unwell this time and her vital signs show her BP: 130/85, HR: 101, RR: 22, & Temp: 37.9

The pathologist describes the wall of the gallbladder as ‘firm and thickened’. Can you explain why this is? (5)

A

Due to it being swollen over a long period of time and chronic inflammation leading to fibrosis

27
Q

A 32 year old man has been suffering with depression for some time. After a series of personal problems, he decides that he does not want to live anymore and plans to commit suicide. He takes an overdose of paracetamol. A friend finds all the empty pockets and takes him straight to A&E.

What is the mechanism of action of paracetamol?

A

It acts centrally e.g. COX3 reduces fever, and it acts peripherally e.g. COX2 to reduce inflammation and pain

28
Q

A 32 year old man has been suffering with depression for some time. After a series of personal problems, he decides that he does not want to live anymore and plans to commit suicide. He takes an overdose of paracetamol. A friend finds all the empty pockets and takes him straight to A&E.

What is the maximum dosage of paracetamol an adult can take in a day?

A

Upto 4000mg/day or 500-1000mg every 4-6 hours

29
Q

A 32 year old man has been suffering with depression for some time. After a series of personal problems, he decides that he does not want to live anymore and plans to commit suicide. He takes an overdose of paracetamol. A friend finds all the empty pockets and takes him straight to A&E.

How is paracetamol metabolised and excreted?

A

Paracetamol, also known as acetaminophen, is primarily metabolized in the liver through three main pathways: glucuronidation, sulfation, and oxidation.

Glucuronidation: About 50-55% of paracetamol is metabolized via this pathway. Glucuronidation involves the addition of a glucuronic acid group to paracetamol, making it more water-soluble and easier for the body to excrete. The conjugation reaction is catalyzed by the enzyme uridine 5’-diphospho-glucuronosyltransferase (UGT).

Sulfation: Around 30% of paracetamol is metabolized via sulfation, which similarly involves the addition of a sulfate group to paracetamol, making it more water-soluble for easier excretion. The sulfation is primarily mediated by the enzyme sulfotransferase.

Oxidation: Approximately 5-15% of paracetamol undergoes oxidative metabolism via the cytochrome P450 enzyme system, specifically CYP2E1, CYP1A2, and CYP3A4. This pathway produces a reactive metabolite known as N-acetyl-p-benzoquinone imine (NAPQI), which is highly toxic and can cause liver damage. Under normal circumstances, this metabolite is immediately detoxified by conjugation with glutathione, a substance produced by the body. However, when paracetamol is taken in large amounts, the body’s glutathione reserves can be depleted, allowing NAPQI to accumulate and cause damage.

The glucuronide and sulfate conjugates of paracetamol, as well as the detoxified NAPQI, are then excreted in the urine. Small amounts of unmetabolized paracetamol may also be excreted directly in the urine.

30
Q

A 32 year old man has been suffering with depression for some time. After a series of personal problems, he decides that he does not want to live anymore and plans to commit suicide. He takes an overdose of paracetamol. A friend finds all the empty pockets and takes him straight to A&E.

When he arrives at A&E, the patient tells the doctor that he has taken 28x 500mg tablets 2 hours before he arrived. The doctor needs to test for paracetamol levels in the patient’s blood.

When should he do the blood test and why?

A

After 4 hours as it’s still being absorbed. It would be underestimated if the blood test was done early

31
Q

A 32 year old man has been suffering with depression for some time. After a series of personal problems, he decides that he does not want to live anymore and plans to commit suicide. He takes an overdose of paracetamol. A friend finds all the empty pockets and takes him straight to A&E.

When he arrives at A&E, the patient tells the doctor that he has taken 28x 500mg tablets 2 hours before he arrived. The doctor needs to test for paracetamol levels in the patient’s blood.

What complications can an overdose of paracetamol cause?

A

Hepatotoxicity, renal failure, metabolic acidosis

32
Q

A 32 year old man has been suffering with depression for some time. After a series of personal problems, he decides that he does not want to live anymore and plans to commit suicide. He takes an overdose of paracetamol. A friend finds all the empty pockets and takes him straight to A&E.

When he arrives at A&E, the patient tells the doctor that he has taken 28x 500mg tablets 2 hours before he arrived. The doctor needs to test for paracetamol levels in the patient’s blood.

The blood test result shows elevated paracetamol levels and treatment needs to be given.

What drug would you give and how does it work?

A

In cases of paracetamol (acetaminophen) overdose, the primary treatment is N-acetylcysteine (NAC).

N-acetylcysteine works as a precursor to glutathione, which is a potent antioxidant naturally produced by the body. Glutathione plays a critical role in the detoxification of the harmful metabolite N-acetyl-p-benzoquinone imine (NAPQI), produced when paracetamol is metabolized in the liver. NAPQI is highly reactive and can cause severe liver damage if it is not quickly neutralized by glutathione.

Under normal circumstances, the body can produce enough glutathione to detoxify NAPQI. However, in cases of paracetamol overdose, the body’s glutathione reserves can be depleted, allowing NAPQI to accumulate and cause damage.

By providing the body with N-acetylcysteine, more glutathione can be synthesized, enhancing the detoxification of NAPQI and reducing the risk of liver damage.

Treatment with N-acetylcysteine is most effective when initiated within 8 hours of a paracetamol overdose. The longer the delay in administering N-acetylcysteine, the less effective it is likely to be because more damage may have already occurred. As a result, N-acetylcysteine is often given as soon as a paracetamol overdose is suspected, even before blood test results confirm elevated paracetamol levels.

While N-acetylcysteine is generally well-tolerated, it can cause side effects such as nausea, vomiting, rash, and rarely, serious allergic reactions. It is usually administered orally or intravenously under medical supervision.

33
Q

A 32 year old man has been suffering with depression for some time. After a series of personal problems, he decides that he does not want to live anymore and plans to commit suicide. He takes an overdose of paracetamol. A friend finds all the empty pockets and takes him straight to A&E.

When he arrives at A&E, the patient tells the doctor that he has taken 28x 500mg tablets 2 hours before he arrived. The doctor needs to test for paracetamol levels in the patient’s blood.

The blood test result shows elevated paracetamol levels and treatment needs to be given.

The picture on the left shows a piece of normal liver. The picture on the right shows a piece of liver from someone who took paracetamol overdose.
What pathological process does this show? (6)

A

Image