Case Study 2 - Chronic Inflammation Flashcards
A 42 year old man presents to the Surgical Assessment Unit with gradual onset of severe abdominal pain. It is located in the epigastrium, and he has been feeling nauseated and vomited 3 times. He tells you that he is known to have gallstones and has been previously admitted to hospital with an attack of “biliary colic”. On examination he is markedly tender in the epigastrium. His BP: 95/54 and HR: 110. He reports that he has not felt the need to pass urine for many hours.
What do you think could be wrong with our patient?
The low blood pressure in this case can indeed be attributed to dehydration from vomiting, and the systemic effects of inflammation, such as vasodilation induced by cytokines like nitric oxide. Additionally, acute cholecystitis can lead to hypoperfusion of organs, including the kidneys, which contributes to decreased urine output and the risk of acute renal failure.
The combination of symptoms, including severe epigastric pain, nausea, vomiting, and low blood pressure, supports the diagnosis of acute cholecystitis. The potential complications, such as systemic inflammation impacting multiple organ systems, highlight the importance of prompt evaluation and management.
A 42 year old man presents to the Surgical Assessment Unit with gradual onset of severe abdominal pain. It is located in the epigastrium, and he has been feeling nauseated and vomited 3 times. He tells you that he is known to have gallstones and has been previously admitted to hospital with an attack of “biliary colic”. On examination he is markedly tender in the epigastrium. His BP: 95/54 and HR: 110. He reports that he has not felt the need to pass urine for many hours.
What are the complications associated with having gallstones
Jaundice, acute pancreatitis, acute cholecystitis, acute cholangitis, acute polycystitis, gallstone ileus, cholangeo carcinoma
A 42 year old man presents to the Surgical Assessment Unit with gradual onset of severe abdominal pain. It is located in the epigastrium, and he has been feeling nauseated and vomited 3 times. He tells you that he is known to have gallstones and has been previously admitted to hospital with an attack of “biliary colic”. On examination he is markedly tender in the epigastrium. His BP: 95/54 and HR: 110. He reports that he has not felt the need to pass urine for many hours.
What treatment would you give to our patient at this stage?
Antibiotics, painkillers,
IV fluid to bring up BP and prevent acute renal failure, antiemetic
A 42 year old man presents to the Surgical Assessment Unit with gradual onset of severe abdominal pain. It is located in the epigastrium, and he has been feeling nauseated and vomited 3 times. He tells you that he is known to have gallstones and has been previously admitted to hospital with an attack of “biliary colic”. On examination he is markedly tender in the epigastrium. His BP: 95/54 and HR: 110. He reports that he has not felt the need to pass urine for many hours.
The doctors are concerned and prescribe some IV fluids and some codeine and paracetamol for the pain. This does not work initially so they need to think of something else to prescribe.
What is the ‘analgesic ladder’?
The analgesic ladder is indeed a guideline used in the management of pain, and it outlines three steps of increasing potency in pain management. Your description aligns with the basic principles of the analgesic ladder:
Step 1 - Non-Opioid Analgesics: Simple painkillers like paracetamol (acetaminophen) fall into this category. These are typically used for mild to moderate pain.
Step 2 - Mild Opioids: Intermediate painkillers, as you mentioned “cocodemal” (which might refer to a combination of codeine and paracetamol), are part of this step. These are utilized for moderate to moderately severe pain.
Step 3 - Opioids: Strong opioids, like morphine, oxycodone, or fentanyl, are reserved for severe pain that is not adequately controlled by non-opioid and weak opioid analgesics.
The idea behind the ladder is to start with the least potent and least risky medications and progress to stronger options as needed, tailoring the treatment to the individual patient’s pain level. It’s a structured approach to pain management that aims to balance effective pain relief with minimizing the risk of side effects and dependence on potent medications.
A 42 year old man presents to the Surgical Assessment Unit with gradual onset of severe abdominal pain. It is located in the epigastrium, and he has been feeling nauseated and vomited 3 times. He tells you that he is known to have gallstones and has been previously admitted to hospital with an attack of “biliary colic”. On examination he is markedly tender in the epigastrium. His BP: 95/54 and HR: 110. He reports that he has not felt the need to pass urine for many hours.
The doctors are concerned and prescribe some IV fluids and some codeine and paracetamol for the pain. This does not work initially so they need to think of something else to prescribe.
How does the drug ‘codeine’ work to reduce pain? What are the side effects?
Metabolism: Codeine is indeed a prodrug and needs to be metabolized to its active form, morphine, primarily in the liver, by the enzyme cytochrome P450 2D6.
Action on Adenylate Cyclase: Morphine, once formed, acts on the central nervous system. One of its effects is the inhibition of adenylate cyclase. Adenylate cyclase is an enzyme responsible for converting ATP (adenosine triphosphate) into cAMP (cyclic adenosine monophosphate).
Reduction in Intracellular cAMP Levels: Inhibition of adenylate cyclase by morphine results in a reduction of intracellular cAMP levels. cAMP is a secondary messenger that plays a role in various cellular processes, including the transmission of pain signals.
Inhibition of Voltage-Gated Calcium Channels: The decrease in cAMP levels leads to the inhibition of voltage-gated calcium channels. These channels are crucial for the transmission of signals in neurons.
Opening of Voltage-Gated K+ Channels: Simultaneously, morphine causes the opening of voltage-gated potassium (K+) channels. This action contributes to the inhibition of depolarization in neurons, reducing the excitability of nerve cells.
Inhibition of Neurotransmitter Release: By modulating these cellular processes, morphine inhibits the release of neurotransmitters involved in pain transmission, such as GABA, dopamine, and substance P.
Overall Inhibition of Nociceptive Neurotransmission: The combined effects on cAMP, calcium channels, and neurotransmitter release lead to the overall inhibition of nociceptive (pain) neurotransmission.
A 42 year old man presents to the Surgical Assessment Unit with gradual onset of severe abdominal pain. It is located in the epigastrium, and he has been feeling nauseated and vomited 3 times. He tells you that he is known to have gallstones and has been previously admitted to hospital with an attack of “biliary colic”. On examination he is markedly tender in the epigastrium. His BP: 95/54 and HR: 110. He reports that he has not felt the need to pass urine for many hours.
The doctors are concerned and prescribe some IV fluids and some codeine and paracetamol for the pain. This does not work initially so they need to think of something else to prescribe.
The doctors request for some tests to be done. The patient has some blood tests done, a chest and abdominal x-ray, and he is catheterised. The blood results come back and show a WCC of 16, CRP of 240 and an amylase of 1200.
What is amylase and what are possible reasons for a raised amylase?
Amylase is an enzyme produced primarily by the pancreas and salivary glands. Its main function is to break down complex carbohydrates (starches) into simpler sugars, facilitating their absorption in the digestive system. Amylase is released into the digestive tract to aid in the digestion of carbohydrates.
Elevated levels of amylase in the blood, known as hyperamylasemia, can be indicative of various conditions, with the most common association being pancreatitis. Pancreatitis is inflammation of the pancreas, and during this inflammatory process, damaged pancreatic cells release amylase into the bloodstream. Therefore, a raised amylase level in the blood is often a marker of pancreatic injury.
Possible reasons for a raised amylase include:
Pancreatitis: This is the most common cause of elevated amylase levels. Acute pancreatitis, which involves sudden inflammation of the pancreas, can lead to a significant release of amylase into the blood. Chronic pancreatitis, a long-term inflammation, can also cause persistently elevated amylase levels.
Obstruction of the Pancreatic Duct: Any blockage or obstruction of the pancreatic duct, which prevents the normal flow of pancreatic juices, can lead to increased amylase levels. This can be caused by conditions such as gallstones or tumors.
Salivary Gland Disorders: While pancreatic amylase is the major contributor to amylase levels in the blood, salivary glands also produce a smaller amount. Disorders affecting the salivary glands, such as mumps, can cause an increase in amylase.
Perforated Peptic Ulcer: A perforation in the stomach or duodenal ulcer can sometimes lead to leakage of digestive enzymes, including amylase, into the abdominal cavity, causing elevated blood levels.
A 42 year old man presents to the Surgical Assessment Unit with gradual onset of severe abdominal pain. It is located in the epigastrium, and he has been feeling nauseated and vomited 3 times. He tells you that he is known to have gallstones and has been previously admitted to hospital with an attack of “biliary colic”. On examination he is markedly tender in the epigastrium. His BP: 95/54 and HR: 110. He reports that he has not felt the need to pass urine for many hours.
The doctors are concerned and prescribe some IV fluids and some codeine and paracetamol for the pain. This does not work initially so they need to think of something else to prescribe.
The doctors request for some tests to be done. The patient has some blood tests done, a chest and abdominal x-ray, and he is catherised. The blood results come back and show a WCC of 16, CRP of 240 and an amylase of 1200.
What does the raised CRP and WCC mean? Do you have a diagnosis?
The elevated CRP (C-reactive protein) and WCC (white cell count) in the blood tests are indicative of an inflammatory process in the body. In the context of the clinical presentation you provided, including severe epigastric pain, nausea, vomiting, and an elevated amylase level, these findings strongly suggest acute pancreatitis.
Elevated CRP: C-reactive protein is an acute-phase reactant that increases in response to inflammation, infection, or tissue injury. A markedly elevated CRP level of 240 is consistent with a significant inflammatory process. In the case of acute pancreatitis, inflammation of the pancreas is the likely cause.
Elevated WCC: The white cell count (WCC) is a measure of the number of white blood cells in the blood. An elevated WCC (16,000 in this case) indicates an immune system response to an infection or inflammation. In acute pancreatitis, the inflammatory process triggers an immune response, leading to an increase in white blood cells.
These laboratory findings, along with the clinical symptoms and the patient’s history of gallstones, point towards acute pancreatitis as the likely diagnosis. The epigastric tenderness on examination further supports this conclusion. Acute pancreatitis is often associated with gallstones, as they can cause obstruction of the pancreatic duct, leading to inflammation.
A 42 year old man presents to the Surgical Assessment Unit with gradual onset of severe abdominal pain. It is located in the epigastrium, and he has been feeling nauseated and vomited 3 times. He tells you that he is known to have gallstones and has been previously admitted to hospital with an attack of “biliary colic”. On examination he is markedly tender in the epigastrium. His BP: 95/54 and HR: 110. He reports that he has not felt the need to pass urine for many hours.
The doctors are concerned and prescribe some IV fluids and some codeine and paracetamol for the pain. This does not work initially so they need to think of something else to prescribe.
The doctors request for some tests to be done. The patient has some blood tests done, a chest and abdominal x-ray, and he is catherised. The blood results come back and show a WCC of 16, CRP of 240 and an amylase of 1200.
What is pancreatitis and what are the types?
There are two types of inflammation of the pancreas which are acute and chronic. Pancreatitis can be due to gallstones as it blocks the pancreatic duct. This stops flow of pancreatic juice (pancreatic enzymes). An accumulation of pancreatic enzymes which destroys pancreatic tissues can lead to inflammation
A 42 year old man presents to the Surgical Assessment Unit with gradual onset of severe abdominal pain. It is located in the epigastrium, and he has been feeling nauseated and vomited 3 times. He tells you that he is known to have gallstones and has been previously admitted to hospital with an attack of “biliary colic”. On examination he is markedly tender in the epigastrium. His BP: 95/54 and HR: 110. He reports that he has not felt the need to pass urine for many hours.
The doctors are concerned and prescribe some IV fluids and some codeine and paracetamol for the pain. This does not work initially so they need to think of something else to prescribe.
The doctors request for some tests to be done. The patient has some blood tests done, a chest and abdominal x-ray, and he is catherised. The blood results come back and show a WCC of 16, CRP of 240 and an amylase of 1200.
What are the causes of pancreatitis and what do you think the cause is in this case?
Gallstones: Gallstones are a significant cause of pancreatitis. When a gallstone obstructs the common bile duct or the pancreatic duct, it can lead to inflammation of the pancreas.
Alcohol Consumption: Heavy and prolonged alcohol use is another common cause of pancreatitis. It can lead to direct damage to the pancreatic tissue.
Trauma: Trauma to the pancreas, such as abdominal injuries, can result in pancreatitis.
Hypertriglyceridemia: Elevated levels of triglycerides in the blood can be associated with pancreatitis. Triglycerides can accumulate in the pancreatic cells, leading to inflammation.
Cystic Fibrosis: Individuals with cystic fibrosis, a genetic disorder affecting the respiratory and digestive systems, may be at an increased risk of pancreatitis.
Certain Medications: Some medications, including certain antibiotics, anti-seizure drugs, and diuretics, have been associated with pancreatitis.
Infections: Viral or bacterial infections, particularly mumps, can cause pancreatitis.
Hypercalcemia: Elevated levels of calcium in the blood can be a contributing factor.
ERCP (Endoscopic Retrograde Cholangiopancreatography): A medical procedure used for examining and treating conditions of the liver, gallbladder, and pancreas. It carries a risk of inducing pancreatitis.
Given the patient’s history of gallstones, the location and nature of the abdominal pain, and the associated symptoms, gallstones blocking the pancreatic duct is a likely cause in this case. This obstruction would lead to the release of digestive enzymes, causing inflammation and the symptoms of pancreatitis.
A 42 year old man presents to the Surgical Assessment Unit with gradual onset of severe abdominal pain. It is located in the epigastrium, and he has been feeling nauseated and vomited 3 times. He tells you that he is known to have gallstones and has been previously admitted to hospital with an attack of “biliary colic”. On examination he is markedly tender in the epigastrium. His BP: 95/54 and HR: 110. He reports that he has not felt the need to pass urine for many hours.
The doctors are concerned and prescribe some IV fluids and some codeine and paracetamol for the pain. This does not work initially so they need to think of something else to prescribe.
The doctors request for some tests to be done. The patient has some blood tests done, a chest and abdominal x-ray, and he is catherised. The blood results come back and show a WCC of 16, CRP of 240 and an amylase of 1200.
A week later, the patient has recovered sufficiently and is discharged home. He is advised to attend an appointment with the surgeons to discuss removing his gallbladder but he decides not to bother. He has several further attacks of abdominal pain but does not come into hospital. 1 year later, the pain is so sever that he returns.
What has caused our patient’s return to hospital?
Can you explain the pathological process that is occurring?
The patient’s return to the hospital, especially after multiple episodes of abdominal pain and a history of gallstones, suggests a progression of the underlying condition, likely involving the pancreas. The repeated attacks of abdominal pain and the decision to forego gallbladder removal could lead to complications, such as chronic pancreatitis.
Pathological Process - Chronic Pancreatitis:
Recurrent Acute Pancreatitis: The initial attacks of abdominal pain, nausea, and vomiting described in the patient’s history were likely episodes of acute pancreatitis, often associated with gallstones obstructing the pancreatic duct.
Inflammation and Tissue Damage: With each episode of acute pancreatitis, there is inflammation of the pancreas, and over time, this inflammatory process can lead to damage and scarring (fibrosis) of pancreatic tissue.
Persistent Symptoms: The patient’s decision to avoid gallbladder removal may have allowed the underlying cause (likely gallstones) to persist, contributing to the recurrence of acute pancreatitis.
Chronic Pancreatitis Development: As the inflammatory process continues and becomes persistent, it transitions into chronic pancreatitis. Chronic pancreatitis is characterized by ongoing inflammation, fibrosis, and the eventual loss of normal pancreatic function.
Symptoms of Chronic Pancreatitis: Patients with chronic pancreatitis may experience recurrent abdominal pain, weight loss, malabsorption, and diabetes. The pancreas becomes less able to produce digestive enzymes and insulin, leading to these symptoms.
Return to Hospital: The return to the hospital, especially after a year of experiencing severe abdominal pain, may signify worsening of chronic pancreatitis, the development of complications, or a new acute exacerbation of the disease.
A 15 year old girl presents to A&E with shortness of breath. She has an audible ‘wheeze’. A diagnosis of acute asthma is made and she is given some oxygen, some nebulisers and inhalers. A few days later she is discharged. She continues to have recurrent asthma attacks, and notices it is related to when she is exposed to dust and cold weather.
What is asthma?
Inflammation of the conducting airways which can lead to bronchoconstriction and bronchospasm
A 15 year old girl presents to A&E with shortness of breath. She has an audible ‘wheeze’. A diagnosis of acute asthma is made and she is given some oxygen, some nebulisers and inhalers. A few days later she is discharged. She continues to have recurrent asthma attacks, and notices it is related to when she is exposed to dust and cold weather.
What can stimulate an asthma attack?
Asthma attacks can be triggered by various factors, and these triggers can vary among individuals. Here are some common triggers for asthma attacks:
Allergies (Atopic Asthma): Allergic asthma is triggered by allergens such as pollen, mold spores, pet dander, and dust mites.
Non-Allergic Triggers:
Cold Air (Non-Atopic - Non-Allergy Induced): Exposure to cold air, especially during winter, can trigger asthma symptoms in some individuals.
Temperature Changes: Rapid changes in temperature, such as going from a warm environment to a cold one, can trigger asthma.
Exercise-Induced Asthma: Physical activity can trigger asthma symptoms, particularly in cold or dry air.
Hyperventilation: Breathing rapidly or hyperventilating can lead to asthma symptoms in some individuals.
Environmental Factors:
Cigarette Smoke: Exposure to tobacco smoke, either firsthand or secondhand, is a common trigger for asthma attacks.
Air Pollution: High levels of air pollution can exacerbate asthma symptoms.
Drug-Induced Asthma:
Beta-Blockers: Certain medications, such as beta-blockers, can trigger asthma symptoms in susceptible individuals.
Occupational Asthma:
Workplace Exposures: Exposure to occupational irritants or allergens, such as asbestos or certain chemicals, can lead to occupational asthma.
Infections:
Respiratory Infections: Viral respiratory infections, such as the common cold or the flu, can exacerbate asthma symptoms.
Gastroesophageal Reflux Disease (GERD): Stomach acid flowing back into the esophagus can trigger asthma symptoms in some individuals.
A 15 year old girl presents to A&E with shortness of breath. She has an audible ‘wheeze’. A diagnosis of acute asthma is made and she is given some oxygen, some nebulisers and inhalers. A few days later she is discharged. She continues to have recurrent asthma attacks, and notices it is related to when she is exposed to dust and cold weather.
What causes the ‘wheeze’ that was heard when our patient came into A&E
Narrowing of the airways
A 15 year old girl presents to A&E with shortness of breath. She has an audible ‘wheeze’. A diagnosis of acute asthma is made and she is given some oxygen, some nebulisers and inhalers. A few days later she is discharged. She continues to have recurrent asthma attacks, and notices it is related to when she is exposed to dust and cold weather.
Below are 2 pictures. The first shows a picture of the airways of someone without asthma. The
second shows the airways of someone who has had asthma for many years.
What are the histological differences and why have they occurred? Label histology where indicated. (1)
Image
A 15 year old girl presents to A&E with shortness of breath. She has an audible ‘wheeze’. A diagnosis of acute asthma is made and she is given some oxygen, some nebulisers and inhalers. A few days later she is discharged. She continues to have recurrent asthma attacks, and notices it is related to when she is exposed to dust and cold weather.
What is ‘salbutamol’ and how does it work?
Salbutamol is a bronchodilator medication commonly used in the treatment of asthma and other respiratory conditions. It is a type of beta-2 adrenergic agonist, and its primary active ingredient is albuterol. Here’s how salbutamol works:
Mechanism of Action:
Activation of Beta-2 Adrenergic Receptors: Salbutamol acts by selectively binding and activating beta-2 adrenergic receptors, which are primarily found on smooth muscle cells in the airways.
Increased Cyclic AMP (cAMP) Production: Activation of the beta-2 receptors leads to an increase in the production of cyclic AMP (cAMP) within the smooth muscle cells.
Activation of Protein Kinase A (PKA): Elevated cAMP levels activate an enzyme called protein kinase A (PKA).
Inhibition of Myosin Phosphorylation: PKA inhibits the phosphorylation of myosin, a protein involved in smooth muscle contraction. Phosphorylation of myosin is a process that leads to muscle contraction.
Smooth Muscle Relaxation: By inhibiting myosin phosphorylation, salbutamol induces smooth muscle relaxation in the bronchioles and bronchi of the respiratory tract.
Bronchodilation: The relaxation of smooth muscle results in the dilation of the airways, making it easier for the individual to breathe.
Additional Effects:
Inhibition of Mast Cell Activation: Salbutamol also has anti-inflammatory effects. It can inhibit the release of bronchoconstrictors, such as histamine and leukotrienes, from mast cells. This action helps to prevent or reverse bronchoconstriction and reduce airway inflammation.
Prevention of Exercise-Induced Bronchoconstriction: Salbutamol can be used before physical activity to prevent exercise-induced bronchoconstriction in individuals with asthma.
Clinical Application:
Salbutamol is commonly administered via inhalation using devices such as metered-dose inhalers (MDIs) or nebulizers.
It is a rescue or reliever medication used to quickly alleviate acute symptoms of bronchoconstriction in asthma or other obstructive airway diseases.
The rapid onset of action and targeted bronchodilator effect make it effective in providing quick relief during asthma attacks.
