Case Study 7 - Thrombosis & Embolism

Question 1

A 28 year old man has been in hospital for 2 days under treatment for
meningitis. He has been treated with IV fluids and IV antibiotics. However, he does not seem to be making much improvement and is diagnosed with septic
shock. One of the
nurses notices a non-blanching rash over his body.

What is meningitis?

Answer 1

Inflammation of the meninges and the CSF. The causes are bacterial, viral, fungal.
3 types: Acute pyogenic Meningitis caused by bacteria.
Aseptic meningitis is caused by viral and is subdivided by acute and subacute meningitis. Chronic meningitis is mostly caused by TB and fungi and lasts longer than the other types of meningitis.

Question 2

A 28 year old man has been in hospital for 2 days under treatment for
meningitis. He has been treated with IV fluids and IV antibiotics. However, he does not seem to be making much improvement and is diagnosed with septic
shock. One of the
nurses notices a non-blanching rash over his body.

What are the complications of meningitis?

Answer 2

thrombocytopenia, platelet consumption (condition: DIC), memory/language problems, hearing/vision loss, limb weakness, gangrene secondary to DIC

Question 3

A 28 year old man has been in hospital for 2 days under treatment for
meningitis. He has been treated with IV fluids and IV antibiotics. However, he does not seem to be making much improvement and is diagnosed with septic
shock. One of the
nurses notices a non-blanching rash over his body.

What are clotting factors and their function?

Answer 3

Factor I (Fibrinogen): Fibrinogen is a protein produced by the liver and is present in plasma. During the coagulation process, fibrinogen is converted into fibrin threads, which weave through the platelets and other blood cells to form a stable blood clot.

Factor II (Prothrombin): Prothrombin is also produced by the liver and is a precursor to thrombin. Thrombin is a key enzyme in the coagulation cascade that converts fibrinogen into fibrin, contributing to the formation of blood clots.

Factor III (Tissue Factor): Tissue factor is not produced by the liver but is present in tissues outside the bloodstream. It initiates the extrinsic pathway of the coagulation cascade when there is tissue injury, activating clotting factors and leading to the formation of thrombin.

Factor VII: This is one of the vitamin K-dependent clotting factors produced by the liver. Factor VII is activated by tissue factor and plays a role in the initiation of the coagulation cascade.

Factor VIII: Another vitamin K-dependent factor, Factor VIII is essential for the intrinsic pathway of coagulation. It acts as a cofactor for Factor IX, helping to activate Factor X.

These clotting factors work together in a complex series of reactions to form a stable blood clot. Disorders or deficiencies in clotting factors can lead to bleeding disorders or excessive blood clotting, both of which can have significant health implications. In the case of the patient with meningitis and septic shock, the non-blanching rash could indicate disseminated intravascular coagulation (DIC), a condition where the clotting system is activated throughout the body, leading to both bleeding and clotting tendencies.

Question 4

A 28 year old man has been in hospital for 2 days under treatment for
meningitis. He has been treated with IV fluids and IV antibiotics. However, he does not seem to be making much improvement and is diagnosed with septic
shock. One of the
nurses notices a non-blanching rash over his body.

A few days later, the tips of two of his fingers start to look darker in colour, and he starts to bleed continually from sites
of needle insertion. (1)

Why have the tips of the patient’s fingers become darker in colour?

Answer 4

Necrosis secondary to ischemia as a result of DIC. DIC causes widespread coagulation throughout the body, clotting causes impaired blood flow, leading to gangrene or necrosis.

Question 5

A 28 year old man has been in hospital for 2 days under treatment for
meningitis. He has been treated with IV fluids and IV antibiotics. However, he does not seem to be making much improvement and is diagnosed with septic
shock. One of the
nurses notices a non-blanching rash over his body.

A few days later, the tips of two of his fingers start to look darker in colour, and he starts to bleed continually from sites
of needle insertion.

Shortly after the change in colour of his fingers, the patient is bleeding from the needle insertion sites. Why do you think this is?

Answer 5

Thrombocytopenia because of DIC

Question 6

A 28 year old man has been in hospital for 2 days under treatment for
meningitis. He has been treated with IV fluids and IV antibiotics. However, he does not seem to be making much improvement and is diagnosed with septic
shock. One of the
nurses notices a non-blanching rash over his body.

A few days later, the tips of two of his fingers start to look darker in colour, and he starts to bleed continually from sites
of needle insertion.

Describe the extrinsic clotting cascade.

Answer 6

The extrinsic clotting cascade is one of the two pathways (the other being the intrinsic pathway) that make up the coagulation cascade, a series of events that lead to the formation of blood clots. The extrinsic pathway is activated by external trauma that causes blood to escape from the vascular system.

Here is an overview of the extrinsic clotting cascade:

Tissue Injury:

The extrinsic pathway is triggered by external trauma that causes blood to escape from blood vessels.
Tissue factor (TF), also known as thromboplastin, is released from damaged tissues.
Initiation:

Tissue factor (TF) combines with Factor VII (FVII) in the presence of calcium ions (Ca2+) to form the tissue factor-Factor VII complex.
This complex activates Factor X.
Amplification:

Activated Factor X (Xa) combines with Factor V (FV) and other cofactors to form the prothrombinase complex.
The prothrombinase complex converts prothrombin (Factor II) into thrombin (Factor IIa).
Thrombin Activation:

Thrombin has a central role in the coagulation cascade.
Thrombin activates platelets, converting fibrinogen (Factor I) into fibrin threads.
Fibrin Formation:

Fibrin threads weave through the platelets and other blood cells, forming a stable blood clot.
This clot helps to seal the wound and prevent further blood loss.
The extrinsic pathway is relatively rapid and is crucial for the initial response to external injuries. Tissue factor, a key component of the extrinsic pathway, is not normally present in the bloodstream but is exposed to blood following tissue injury. This pathway is often measured by the prothrombin time (PT) in laboratory tests, which assesses the function of the extrinsic and common pathways.

Question 7

A 28 year old man has been in hospital for 2 days under treatment for
meningitis. He has been treated with IV fluids and IV antibiotics. However, he does not seem to be making much improvement and is diagnosed with septic
shock. One of the
nurses notices a non-blanching rash over his body.

A few days later, the tips of two of his fingers start to look darker in colour, and he starts to bleed continually from sites
of needle insertion.

Describe the intrinsic clotting cascade.

Answer 7

The intrinsic clotting cascade is one of the two pathways (the other being the extrinsic pathway) that make up the coagulation cascade, a series of events leading to the formation of blood clots. The intrinsic pathway is activated by trauma inside the vascular system, such as endothelial cell injury.

Here is an overview of the intrinsic clotting cascade:

Activation of Intrinsic Pathway:

The intrinsic pathway is initiated by trauma inside the vascular system, which can be caused by factors such as endothelial damage.
Factor XII (Hageman factor) is activated by contact with subendothelial substances exposed by injury.
Activation of Factor XI:

Activated Factor XII activates Factor XI (also known as plasma thromboplastin antecedent).
Activation of Factor IX:

Activated Factor XI, in the presence of calcium ions (Ca2+), activates Factor IX (Christmas factor).
Activation of Factor X:

Activated Factor IX combines with Factor VIII (antihemophilic factor A) and other cofactors to form the tenase complex.
The tenase complex activates Factor X.
Amplification and Common Pathway:

Activated Factor X (Xa) combines with Factor V (proaccelerin) and other cofactors to form the prothrombinase complex.
The prothrombinase complex converts prothrombin (Factor II) into thrombin (Factor IIa).
Thrombin Activation:

Thrombin has a central role in the coagulation cascade.
Thrombin activates platelets and converts fibrinogen (Factor I) into fibrin threads.
Fibrin Formation:

Fibrin threads weave through the platelets and other blood cells, forming a stable blood clot.
This clot helps to seal the wound and prevent further blood loss.
The intrinsic pathway is named for the clotting factors involved being present in the blood (intrinsic to the blood). This pathway is often measured by the activated partial thromboplastin time (aPTT) in laboratory tests.

Question 8

A 28 year old man has been in hospital for 2 days under treatment for
meningitis. He has been treated with IV fluids and IV antibiotics. However, he does not seem to be making much improvement and is diagnosed with septic
shock. One of the
nurses notices a non-blanching rash over his body.

A few days later, the tips of two of his fingers start to look darker in colour, and he starts to bleed continually from sites
of needle insertion.

What are the 3 factors that lead to thrombosis?

Answer 8

The Virchow’s triad outlines three major factors that contribute to the development of thrombosis:

Endothelial Injury:

Damage to the endothelial lining of blood vessels is a crucial factor in the initiation of thrombosis.
Endothelial injury can result from various factors, including trauma, inflammation, hypertension, and turbulent blood flow.
When the endothelium is damaged, it exposes underlying tissues and triggers the coagulation cascade.
Hypercoagulability:

Hypercoagulability refers to a state in which there is an increased tendency for blood clot formation.
This can be due to various conditions, including genetic factors (such as inherited clotting disorders), acquired disorders (like antiphospholipid syndrome), certain medications, and malignancies.
An imbalance in the coagulation and anticoagulation factors can promote excessive clotting.
Abnormal Blood Flow:

Disturbed or abnormal blood flow can contribute to thrombosis.
Stasis (sluggish blood flow) or turbulence in the bloodstream can lead to the activation of clotting factors.
Conditions such as immobility, long periods of sitting, or vascular abnormalities can contribute to abnormal blood flow.

Question 9

A 28 year old man has been in hospital for 2 days under treatment for
meningitis. He has been treated with IV fluids and IV antibiotics. However, he does not seem to be making much improvement and is diagnosed with septic
shock. One of the
nurses notices a non-blanching rash over his body.

A few days later, the tips of two of his fingers start to look darker in colour, and he starts to bleed continually from sites
of needle insertion.

What are the causes of disseminated intravascular coagulation (DIC) and what caused it
in our patient’s case?

Answer 9

Causes of DIC:

Infection:

Bacterial, viral, fungal, or parasitic infections can trigger DIC.
In the context of infection, bacterial toxins can activate the coagulation cascade. For example, in sepsis, bacterial endotoxins may activate Factor XII, initiating the intrinsic pathway of coagulation.
Trauma or Injury:

Physical trauma, extensive surgery, or severe tissue injury can lead to DIC.
The tissue factor pathway is activated when tissue factor is released from damaged sub-endothelial tissues. This initiates the extrinsic pathway, leading to the activation of clotting factors and widespread clot formation.
The pro-coagulant pathway can be activated by injury to vascular endothelial cells or the liver. Endothelial cell injury can lead to the release of procoagulant factors, particularly thromboxane A2. Liver injury can result in the release of procoagulant factors, especially prothrombin.
Cytokine Release:

Inflammatory conditions can result in the release of cytokines, which in turn can contribute to DIC.
Cytokines can activate the coagulation cascade, leading to widespread clotting.
In the Patient’s Case:
In the case of the 28-year-old man with meningitis and septic shock:

The underlying infection (meningitis) is a significant trigger for DIC. The release of bacterial toxins, possibly activating Factor XII and initiating the intrinsic pathway, can contribute to the widespread clotting observed.
Septic shock is associated with a dysregulated inflammatory response, leading to the release of cytokines. This inflammatory state can further contribute to the activation of the coagulation cascade, exacerbating DIC.

Question 10

A 48 year old woman is involved in a road traffic collision. She fractures her femur and is referred to the orthopaedic team. They are in the process of
getting her ready to
take to theatre for an
operation to repair the
fracture when they
notice some changes to
the patient. They notice
that she has become
short of breath but also
appears very agitated.

What do you think could account for the symptoms our patient is showing?

Answer 10

The symptoms described in the case are indicative of a potential fat embolism syndrome (FES). Fat embolism occurs when fat globules, usually from the bone marrow or adipose tissue, enter the bloodstream and travel to the lungs, causing a blockage in the pulmonary vessels. This can lead to a range of symptoms, including respiratory and neurological manifestations.

Here’s a breakdown of how fat embolism can occur and the associated symptoms:

Mechanism of Fat Embolism:

Fractures, especially long bone fractures like the femur, can lead to the release of fat globules into the bloodstream.
Rupture of sinusoids in the bone marrow or small venules allows marrow or adipose tissue to enter the vascular space.
Symptoms of Fat Embolism Syndrome (FES):

Respiratory Symptoms: Shortness of breath is a common early sign, and it can progress to respiratory distress or failure. Hypoxemia (low oxygen levels) can occur.
Neurological Symptoms: Agitation and confusion are common neurological manifestations. More severe cases can lead to seizures or even coma.
Hematological Symptoms: FES can lead to anemia and thrombocytopenia (low platelet count).
Formation of Fat Embolus:

Fat globules, along with hematopoietic cells like red blood cells (RBCs) and platelets, can travel together to form an embolus.
The embolus can lodge in the pulmonary vessels, causing obstruction.

Question 11

A 48 year old woman is involved in a road traffic collision. She fractures her femur and is referred to the orthopaedic team. They are in the process of
getting her ready to
take to theatre for an
operation to repair the
fracture when they
notice some changes to
the patient. They notice
that she has become
short of breath but also
appears very agitated.

What are the causes of this condition?

Answer 11

fractures of long bones, soft tissue trauma, burns

Question 12

A 48 year old woman is involved in a road traffic collision. She fractures her femur and is referred to the orthopaedic team. They are in the process of
getting her ready to
take to theatre for an
operation to repair the
fracture when they
notice some changes to
the patient. They notice
that she has become
short of breath but also
appears very agitated.

How does it cause its pathological effects?

Answer 12

Mechanical Obstruction:

Fat emboli, along with associated red blood cells (RBCs) and platelets, aggregate and obstruct small blood vessels, particularly in the pulmonary and cerebral microvasculature.
This mechanical obstruction hinders normal blood flow, leading to impaired oxygen exchange and tissue perfusion.
Biochemical Injury:

Free fatty acids are released from fat globules that have entered the bloodstream. These fatty acids can be toxic to the vascular endothelium.
The toxic effects of free fatty acids contribute to injury of the vascular walls. This injury, in turn, triggers a cascade of events:
Platelet Aggregation: The damaged vascular walls promote platelet aggregation, further contributing to clot formation and obstruction.
Granulocyte Recruitment: Inflammation is initiated, and granulocytes (a type of white blood cell) are recruited to the site of injury.
Thrombosis: The combination of inflammation and platelet aggregation can lead to the formation of small blood clots (thrombosis) within the vessels.
Inflammatory Response:

The biochemical injury and ensuing thrombosis contribute to an inflammatory response.
Inflammation can exacerbate the obstruction of blood vessels and contribute to the clinical symptoms, including agitation and respiratory distress.

Question 13

A 48 year old woman is involved in a road traffic collision. She fractures her femur and is referred to the orthopaedic team. They are in the process of
getting her ready to
take to theatre for an
operation to repair the
fracture when they
notice some changes to
the patient. They notice
that she has become
short of breath but also
appears very agitated.

What complications can develop?

Answer 13

chronic inflammation, shock, infarction, lung failure, organ failure, fat embolism syndrome where you have embolic fat globules passing to the blood vessels in the lungs or brain, thrombocytopenia, anaemia, symptoms of mechanical obstruction e.g. if in brain: disorientation, confusion, seizures, coma, stroke, in lungs shortness of breath, chest tightness, hyperventilation

Question 14

A 48 year old woman is involved in a road traffic collision. She fractures her femur and is referred to the orthopaedic team. They are in the process of
getting her ready to
take to theatre for an
operation to repair the
fracture when they
notice some changes to
the patient. They notice
that she has become
short of breath but also
appears very agitated.

What does the histology picture below show? (2)

Answer 14

Image

Question 15

A 48 year old woman is involved in a road traffic collision. She fractures her femur and is referred to the orthopaedic team. They are in the process of
getting her ready to
take to theatre for an
operation to repair the
fracture when they
notice some changes to
the patient. They notice
that she has become
short of breath but also
appears very agitated.

What is the definition of ‘embolism’?

Answer 15

An embolus is a detached intravascular solid, liquid or gas mass that is carried by the blood from its point of origin to a distant site where they can often cause tissue dysfunction or infarction

Question 16

A 48 year old woman is involved in a road traffic collision. She fractures her femur and is referred to the orthopaedic team. They are in the process of
getting her ready to
take to theatre for an
operation to repair the
fracture when they
notice some changes to
the patient. They notice
that she has become
short of breath but also
appears very agitated.

What are the other causes of embolism?

Answer 16

gas, amniotic fluid, thromboembolism, cholesterol embolism

Question 17

A 17-year-old girl is not feeling well. She was diagnosed with type 1 diabetes 2 months ago but has been struggling with her control. She has been at college today but forgot to take her insulin dose with her lunch and cannot find her pen
device. She feels very
tired and thirsty. She
begins to feel sick and
decides to take herself to
hospital.

What is the pathology behind the development of type 1 diabetes?

Answer 17

Your description of the pathology behind the development of type 1 diabetes (T1D) is accurate. Type 1 diabetes is an autoimmune condition characterized by the destruction of insulin-producing beta cells in the pancreas. The two main causes you mentioned are key factors in the development of T1D:

Genetic Susceptibility:

There is a strong genetic component to type 1 diabetes. Individuals with a family history of T1D have an increased risk of developing the condition.
The major genetic susceptibility factor is linked to the human leukocyte antigen (HLA) gene cluster on chromosome 6, specifically the HLA class II genes. Certain HLA genotypes, such as those in the HLA-DR and HLA-DQ regions, are associated with an increased risk of T1D.
These genetic factors contribute to an increased susceptibility to the presentation of self-antigens to T cells, initiating an autoimmune response.
Environmental Factors:

Environmental factors play a crucial role in triggering the autoimmune response leading to T1D.
Viral infections, particularly those involving enteroviruses, have been implicated in the development of T1D. Molecular mimicry is a concept where viral antigens resemble self-antigens, leading to an immune response against both the virus and the body’s own tissues.
In susceptible individuals, the immune system may mistakenly target the beta cells in the pancreas, considering them as foreign or infected due to the molecular mimicry between viral and self-antigens.
This autoimmune response results in the destruction of beta cells, leading to a reduction or complete loss of insulin production.

Question 18

A 17-year-old girl is not feeling well. She was diagnosed with type 1 diabetes 2 months ago but has been struggling with her control. She has been at college today but forgot to take her insulin dose with her lunch and cannot find her pen
device. She feels very
tired and thirsty. She
begins to feel sick and
decides to take herself to
hospital.

What hormones does the pancreas produce and which cells secrete them?

Answer 18

The pancreas is a gland with both endocrine and exocrine functions. The endocrine function involves the secretion of hormones, while the exocrine function involves the production of digestive enzymes. The key hormones produced by the endocrine cells of the pancreas are insulin, glucagon, somatostatin, and pancreatic polypeptide. Here’s a breakdown of these hormones and the cells that secrete them:

Insulin:

Producing Cells: Beta cells (β-cells) in the islets of Langerhans.
Function: Stimulates the uptake of glucose by cells, especially muscle and adipose tissue. It promotes the storage of glucose as glycogen in the liver and muscle cells, lowering blood glucose levels.
Glucagon:

Producing Cells: Alpha cells (α-cells) in the islets of Langerhans.
Function: Increases blood glucose levels by promoting the breakdown of glycogen in the liver (glycogenolysis) and the conversion of amino acids into glucose (gluconeogenesis).
Somatostatin:

Producing Cells: Delta cells (δ-cells) in the islets of Langerhans.
Function: Inhibits the release of both insulin and glucagon, helping to regulate and maintain blood glucose levels. It also slows down the absorption of nutrients in the digestive tract.
Pancreatic Polypeptide:

Producing Cells: F cells in the pancreatic islets.
Function: Inhibits pancreatic exocrine secretion and may play a role in regulating the release of other pancreatic hormones.

Question 19

A 17-year-old girl is not feeling well. She was diagnosed with type 1 diabetes 2 months ago but has been struggling with her control. She has been at college today but forgot to take her insulin dose with her lunch and cannot find her pen
device. She feels very
tired and thirsty. She
begins to feel sick and
decides to take herself to
hospital.

What is the normal role of the insulin hormone in the body?

Answer 19

it’s an anabolic hormone. The principal metabolic function is to metabolise the glucose uptake and lipogenesis but decreases lipolysis. In striated muscle it increases glucose uptake, glucose synthesis as well as protein synthesis. In the liver it decreases gluconeogenesis but it increases glycogen synthesis and lipogenesis

Question 20

A 17-year-old girl is not feeling well. She was diagnosed with type 1 diabetes 2 months ago but has been struggling with her control. She has been at college today but forgot to take her insulin dose with her lunch and cannot find her pen
device. She feels very
tired and thirsty. She
begins to feel sick and
decides to take herself to
hospital.

When our patient arrives at hospital she feels even worse. The doctor who
comes to speak to her notices a sweet smell of her breath. Her BP is 100/50 and her HR is 104. He notices that she is
breathing very deeply. He does a blood glucose test and the result is 22.1
mmol/l. He also performs an arterial blood gas test and notices she has a
metabolic acidosis. Her urine dipstick shows the presence of ketones.

What do you think the diagnosis is and why has she developed this?

Answer 20

Diabetic Ketoacidosis (DKA):
DKA is a serious and potentially life-threatening complication of diabetes, particularly in individuals with type 1 diabetes. It is characterized by hyperglycemia, ketosis (presence of ketones in the blood), and metabolic acidosis.

Underlying Processes:

Insulin Deficiency:

Cause: In this case, the patient forgot to take her insulin dose, leading to a lack of insulin.
Effect: Insulin normally inhibits the release of glucagon. Without sufficient insulin, there is an increase in glucagon, leading to increased glycogenolysis and gluconeogenesis. This results in elevated blood glucose levels.
Hyperglycemia and Osmotic Diuresis:

Effect: The increased blood glucose spills over into the urine, leading to osmotic diuresis. This causes polyuria (increased urination), polydipsia (excessive thirst), and dehydration.
Clinical Signs: The patient experiences tiredness, thirst, and feeling sick. The blood pressure decreases (hypotension), and the heart rate increases (tachycardia).
Ketogenesis:

Effect: Insulin deficiency also leads to the activation of lipoprotein lipase, causing the breakdown of adipose tissue and the release of free fatty acids. These fatty acids are oxidized in the liver, leading to the production of ketone bodies (acetoacetate and beta-hydroxybutyrate).
Metabolic Acidosis: The accumulation of ketone bodies results in metabolic acidosis.
Respiratory Compensation:

Effect: The metabolic acidosis triggers respiratory compensation. The increased acidity stimulates the respiratory center, leading to hyperventilation (Kussmaul breathing) in an attempt to eliminate excess carbon dioxide and raise blood pH.

Sweet Smell of Breath:
The sweet smell of her breath is due to the presence of acetone, one of the ketone bodies.

Question 21

A 17-year-old girl is not feeling well. She was diagnosed with type 1 diabetes 2 months ago but has been struggling with her control. She has been at college today but forgot to take her insulin dose with her lunch and cannot find her pen
device. She feels very
tired and thirsty. She
begins to feel sick and
decides to take herself to
hospital.

When our patient arrives at hospital she feels even worse. The doctor who
comes to speak to her notices a sweet smell of her breath. Her BP is 100/50 and her HR is 104. He notices that she is
breathing very deeply. He does a blood glucose test and the result is 22.1
mmol/l. He also performs an arterial blood gas test and notices she has a
metabolic acidosis. Her urine dipstick shows the presence of ketones.

What do you think the cause of the sweet smelling breath is and why does this develop?

Answer 21

The sweet smell of the breath, often described as having a fruity or acetone-like odor, is indeed caused by the presence of ketones, specifically acetoacetate and beta-hydroxybutyrate. This phenomenon is commonly observed in individuals experiencing diabetic ketoacidosis (DKA).

Explanation:

Ketone Production:
When insulin levels are insufficient, as is the case in type 1 diabetes, cells are unable to efficiently utilize glucose for energy.
In the absence of sufficient glucose, the body begins to break down fats for energy, leading to the production of ketone bodies in the liver.
Acetoacetate and beta-hydroxybutyrate are two types of ketone bodies formed during this process.

Ketones in Blood and Breath:
As ketone levels rise in the blood, they can be detected in the breath, giving it a distinctive sweet or fruity odor.
Acetone, a breakdown product of acetoacetate, is particularly responsible for the sweet smell.

Metabolic Acidosis:
The accumulation of ketones in the blood leads to an increase in acidity, resulting in metabolic acidosis.
The metabolic acidosis can cause deep and rapid breathing, known as Kussmaul breathing, as the body attempts to eliminate excess carbon dioxide to compensate for the acidosis.

Clinical Significance:
The presence of ketones in the urine (detected by the urine dipstick) and the sweet smell of the breath are key indicators of DKA.
High blood glucose levels, combined with metabolic acidosis and ketosis, contribute to the overall clinical presentation of DKA.

Question 22

A 17-year-old girl is not feeling well. She was diagnosed with type 1 diabetes 2 months ago but has been struggling with her control. She has been at college today but forgot to take her insulin dose with her lunch and cannot find her pen
device. She feels very
tired and thirsty. She
begins to feel sick and
decides to take herself to
hospital.

When our patient arrives at hospital she feels even worse. The doctor who
comes to speak to her notices a sweet smell of her breath. Her BP is 100/50 and her HR is 104. He notices that she is
breathing very deeply. He does a blood glucose test and the result is 22.1
mmol/l. He also performs an arterial blood gas test and notices she has a
metabolic acidosis. Her urine dipstick shows the presence of ketones.

What does ‘compliance with medications’ mean and why is it important?

Answer 22

“Compliance with medications,” often referred to as medication adherence, refers to the extent to which a patient correctly follows the prescribed regimen for taking medications. This includes taking the right dose, at the right time, and in the right way, as instructed by the healthcare provider. Compliance with medications is crucial for several reasons:

Optimal Treatment Efficacy:

Following the prescribed medication regimen as directed by the healthcare provider ensures that the patient receives the intended therapeutic effect.
Consistent and proper use of medications helps achieve the desired outcomes, manage symptoms, and control the underlying condition effectively.
Disease Management:

For chronic conditions, such as diabetes, adherence to the prescribed medication regimen is vital for managing the disease and preventing complications.
In the case of type 1 diabetes, regular insulin administration is essential for controlling blood glucose levels and preventing acute complications like diabetic ketoacidosis.
Prevention of Complications:

Non-compliance or inconsistent medication use can lead to inadequate disease control, an increased risk of complications, and a higher likelihood of hospitalization.
In the context of diabetes, poor compliance with insulin therapy can result in uncontrolled blood sugar levels, leading to acute complications and long-term health risks.
Quality of Life:

Proper adherence to medications can enhance the overall quality of life by minimizing symptoms, improving functional abilities, and preventing the progression of the disease.
In the case of chronic conditions, maintaining a consistent medication routine helps individuals lead more active and productive lives.

Question 23

A 17-year-old girl is not feeling well. She was diagnosed with type 1 diabetes 2 months ago but has been struggling with her control. She has been at college today but forgot to take her insulin dose with her lunch and cannot find her pen
device. She feels very
tired and thirsty. She
begins to feel sick and
decides to take herself to
hospital.

When our patient arrives at hospital she feels even worse. The doctor who
comes to speak to her notices a sweet smell of her breath. Her BP is 100/50 and her HR is 104. He notices that she is
breathing very deeply. He does a blood glucose test and the result is 22.1
mmol/l. He also performs an arterial blood gas test and notices she has a
metabolic acidosis. Her urine dipstick shows the presence of ketones.

Type 1 diabetics generally take 2 types of insulin. What are the different types and what is the difference between them?

Answer 23

In type 1 diabetes management, individuals often use a combination of two types of insulin: fast-acting insulin and long-acting insulin. These two types of insulin serve different purposes in controlling blood glucose levels throughout the day. Here’s an overview of each type:

Fast-Acting Insulin:

Onset of Action: Fast-acting insulin typically has a rapid onset of action, meaning it starts to work quickly after administration.
Peak Action: It reaches its peak effectiveness within a specific timeframe after administration.
Duration of Action: The duration of action is relatively short, typically lasting a few hours.
Common Use: Fast-acting insulin is used to cover mealtime glucose spikes. It is taken just before or shortly after meals to help control the rise in blood sugar associated with food intake.
Examples of Fast-Acting Insulin:

Insulin lispro
Insulin aspart
Insulin glulisine
Long-Acting Insulin:

Onset of Action: Long-acting insulin has a slower onset of action compared to fast-acting insulin.
Peak Action: Unlike fast-acting insulin, long-acting insulin is designed to provide a more consistent level of insulin over an extended period, so it does not have a distinct peak of action.
Duration of Action: Long-acting insulin is formulated to provide a basal (background) level of insulin that lasts for an extended period, typically up to 24 hours.
Common Use: Long-acting insulin is used to provide a continuous, baseline level of insulin throughout the day and night, helping to maintain stable blood glucose levels between meals and during periods of fasting.
Examples of Long-Acting Insulin:

Insulin glargine (Lantus, Toujeo)
Insulin detemir (Levemir)
Insulin degludec (Tresiba)
Combination Therapy:
Some individuals with type 1 diabetes may use both fast-acting and long-acting insulin to mimic the body’s natural insulin production. This combination helps manage both mealtime glucose spikes and provides a consistent background level of insulin to maintain overall blood glucose control.

Question 24

A 17-year-old girl is not feeling well. She was diagnosed with type 1 diabetes 2 months ago but has been struggling with her control. She has been at college today but forgot to take her insulin dose with her lunch and cannot find her pen
device. She feels very
tired and thirsty. She
begins to feel sick and
decides to take herself to
hospital.

When our patient arrives at hospital she feels even worse. The doctor who
comes to speak to her notices a sweet smell of her breath. Her BP is 100/50 and her HR is 104. He notices that she is
breathing very deeply. He does a blood glucose test and the result is 22.1
mmol/l. He also performs an arterial blood gas test and notices she has a
metabolic acidosis. Her urine dipstick shows the presence of ketones.

How is insulin administered, and what are the different regimens?

Answer 24

Methods of Insulin Administration:

Subcutaneous Injection:

Description: Subcutaneous injections involve injecting insulin into the fatty tissue just beneath the skin using a syringe, insulin pen, or an insulin pump.
Common Devices: Insulin pens, syringes, and insulin pumps are commonly used for subcutaneous injections.
Locations: Common injection sites include the abdomen, thighs, and buttocks.
Insulin Pump:

Description: An insulin pump is a small device that delivers a continuous supply of insulin through a tiny tube (catheter) placed under the skin. It mimics the action of a healthy pancreas.
Continuous Basal Insulin: The pump provides a continuous basal (background) insulin infusion to maintain stable blood glucose levels between meals and overnight.
Bolus Doses: Users can deliver additional insulin bolus doses before meals to cover the rise in blood sugar from food intake.
Intravenous (IV) Administration:

Description: Intravenous administration involves delivering insulin directly into the bloodstream through a vein.
Setting: This method is typically used in hospital settings, especially in critical care situations or during surgical procedures.

Common Insulin Regimens:

Basal-Bolus Regimen:
Description: This regimen involves using both basal (long-acting) insulin and bolus (fast-acting) insulin.
Basal Insulin: Administered once or twice a day to provide a constant background insulin level.
Bolus Insulin: Administered before meals to cover the increase in blood sugar from food.

Sliding Scale Insulin:
Description: Sliding scale insulin is a method of adjusting insulin doses based on the current blood glucose levels.
Variable Dosing: The insulin dose is adjusted based on a sliding scale that correlates with the individual’s blood sugar readings.

Multiple Daily Injections (MDI):
Description: In MDI, individuals take multiple injections of both long-acting (basal) and short-acting (bolus) insulin throughout the day.
Flexibility: Offers flexibility in adjusting insulin doses to match lifestyle and meal patterns.

Continuous Subcutaneous Insulin Infusion (CSII):
Description: Also known as insulin pump therapy, CSII provides a continuous infusion of rapid-acting insulin through a pump.
Continuous Basal Insulin: Mimics the constant background release of insulin.
Bolus Doses: Users can administer additional insulin as needed for meals or corrections.

Question 25

A 17-year-old girl is not feeling well. She was diagnosed with type 1 diabetes 2 months ago but has been struggling with her control. She has been at college today but forgot to take her insulin dose with her lunch and cannot find her pen
device. She feels very
tired and thirsty. She
begins to feel sick and
decides to take herself to
hospital.

When our patient arrives at hospital she feels even worse. The doctor who
comes to speak to her notices a sweet smell of her breath. Her BP is 100/50 and her HR is 104. He notices that she is
breathing very deeply. He does a blood glucose test and the result is 22.1
mmol/l. He also performs an arterial blood gas test and notices she has a
metabolic acidosis. Her urine dipstick shows the presence of ketones.

Our patient is diagnosed with diabetic ketoacidosis. She is given IV fluids and an insulin sliding scale is started immediately. She slowly starts to feel better. The diabetic specialist nurse offers her
some advice about the importance of complying with her insulin treatment.

How does the insulin sliding scale work?

Answer 25

The insulin sliding scale is a method used to adjust insulin doses based on the current blood glucose levels of an individual, particularly in the context of managing hyperglycemia, such as in diabetic ketoacidosis (DKA). It is commonly implemented in hospital settings where close monitoring and rapid adjustments are needed. Here’s how the insulin sliding scale typically works:

Assessment of Blood Glucose Levels:

Blood glucose levels are measured regularly, often using point-of-care testing, to monitor the current level of hyperglycemia.
Insulin Dosage Adjustment:

Based on the blood glucose reading, the healthcare team determines the appropriate insulin dosage using a predetermined sliding scale.
The sliding scale is a chart or set of guidelines that outlines insulin dosage adjustments based on specific blood glucose ranges.
Increasing Insulin Dose with Higher Blood Glucose Levels:

As blood glucose levels rise, the insulin dosage prescribed on the sliding scale increases.
The goal is to provide a higher dose of insulin to bring down elevated blood glucose levels more rapidly.
Decreasing Insulin Dose with Lower Blood Glucose Levels:

Conversely, as blood glucose levels decrease, the insulin dosage is adjusted downward or may be temporarily withheld.
This prevents the risk of hypoglycemia (low blood sugar).
Regular Monitoring and Adjustments:

Blood glucose levels are monitored frequently, and insulin doses are adjusted as needed.
The healthcare team closely observes the patient’s response to treatment and makes adjustments to the sliding scale accordingly.

Question 26

A 17-year-old girl is not feeling well. She was diagnosed with type 1 diabetes 2 months ago but has been struggling with her control. She has been at college today but forgot to take her insulin dose with her lunch and cannot find her pen
device. She feels very
tired and thirsty. She
begins to feel sick and
decides to take herself to
hospital.

When our patient arrives at hospital she feels even worse. The doctor who
comes to speak to her notices a sweet smell of her breath. Her BP is 100/50 and her HR is 104. He notices that she is
breathing very deeply. He does a blood glucose test and the result is 22.1
mmol/l. He also performs an arterial blood gas test and notices she has a
metabolic acidosis. Her urine dipstick shows the presence of ketones.

Our patient is diagnosed with diabetic ketoacidosis. She is given IV fluids and an insulin sliding scale is started immediately. She slowly starts to feel better. The diabetic specialist nurse offers her
some advice about the importance of complying with her insulin treatment.

What can happen if too much insulin is given?

Answer 26

hypoglycaemia - symptoms: shortness of breath, dizziness, sweating

Question 27

A 17-year-old girl is not feeling well. She was diagnosed with type 1 diabetes 2 months ago but has been struggling with her control. She has been at college today but forgot to take her insulin dose with her lunch and cannot find her pen
device. She feels very
tired and thirsty. She
begins to feel sick and
decides to take herself to
hospital.

When our patient arrives at hospital she feels even worse. The doctor who
comes to speak to her notices a sweet smell of her breath. Her BP is 100/50 and her HR is 104. He notices that she is
breathing very deeply. He does a blood glucose test and the result is 22.1
mmol/l. He also performs an arterial blood gas test and notices she has a
metabolic acidosis. Her urine dipstick shows the presence of ketones.

Our patient is diagnosed with diabetic ketoacidosis. She is given IV fluids and an insulin sliding scale is started immediately. She slowly starts to feel better. The diabetic specialist nurse offers her
some advice about the importance of complying with her insulin treatment.

How is the pathology behind type 2 diabetes different to type 1 diabetes?

Answer 27

Type 1 Diabetes:
Pathology:

Immune-Mediated Destruction: Type 1 diabetes is primarily an autoimmune condition where the body’s immune system mistakenly targets and destroys the insulin-producing beta cells in the pancreas.
Genetic and Environmental Factors: There is a genetic predisposition to type 1 diabetes, but environmental factors, such as viral infections, can trigger the autoimmune response.
Insulin Deficiency: The destruction of beta cells results in a severe lack of insulin production. Individuals with type 1 diabetes require exogenous insulin for survival.
Type 2 Diabetes:
Pathology:

Insulin Resistance: Type 2 diabetes is characterized by insulin resistance, where the body’s cells become less responsive to the effects of insulin.
Causes of Insulin Resistance:
Obesity: Adipose tissue releases increased adipokines, leading to reduced sensitivity of insulin receptors.
Systemic Inflammation: Proinflammatory cytokines contribute to insulin resistance.
Genetic Factors: Genetic predisposition can play a role in insulin resistance.
Compensatory Hyperinsulinemia: Initially, the pancreas produces more insulin to compensate for insulin resistance. This phase is marked by elevated insulin levels.
Beta Cell Exhaustion: Over time, the beta cells in the pancreas may become exhausted due to the continuous demand for increased insulin production.
Insulin Deficiency: Advanced cases of type 2 diabetes may involve a transition from insulin resistance to insulin deficiency as beta cell function declines.
Shared Features:
Both types of diabetes involve dysregulation of blood glucose levels, leading to hyperglycemia.
Long-term complications, such as cardiovascular disease, neuropathy, and nephropathy, can occur in both types if blood glucose levels are not well-controlled.

Question 28

A 17-year-old girl is not feeling well. She was diagnosed with type 1 diabetes 2 months ago but has been struggling with her control. She has been at college today but forgot to take her insulin dose with her lunch and cannot find her pen
device. She feels very
tired and thirsty. She
begins to feel sick and
decides to take herself to
hospital.

When our patient arrives at hospital she feels even worse. The doctor who
comes to speak to her notices a sweet smell of her breath. Her BP is 100/50 and her HR is 104. He notices that she is
breathing very deeply. He does a blood glucose test and the result is 22.1
mmol/l. He also performs an arterial blood gas test and notices she has a
metabolic acidosis. Her urine dipstick shows the presence of ketones.

Our patient is diagnosed with diabetic ketoacidosis. She is given IV fluids and an insulin sliding scale is started immediately. She slowly starts to feel better. The diabetic specialist nurse offers her
some advice about the importance of complying with her insulin treatment.

What are the glitazones used for and what is their mechanism of action?

Answer 28

It treats the insulin resistance without the production of insulin by the beta cells. It works by acting on par receptors which enhances transcription of insulin responsive genes (genes) which control the release of glucose levels. Increased transcription increases sensitivity of insulin receptors to insulin to treat insulin resistance. It decreases the hepatic gluconeogenesis.