Revising VIA Weak Points

- Asthma Physiology, Anatomy, Pharmacology, Immunology - Diabetes Physiology, Pharmacology, Clinical Skills. - Lower Limb Clinical Skills - CVS Physiology, Pharmacology, Diseases, ECG

What are the two types of macrophages that help in lung defence?

• Alveoli macrophages that phagocytose inhaled air particles

• Interstitial macrophages that are activated if the epithelial barrier is breached

What is important to note about neutrophil involvement in lungs?

• In a healthy lung, neutrophils stay in the blood vessels.

• In an infected lung, neutrophils are recruited and destroy microbes by phagocytosis, ROS and degranulation

  • This can cause pneumonia

What T helper cell and cytokines are involved with autoimmunity and chronic inflammation?

Th₁ secretes IFN gamma to activate macrophages for autoimmunity and chronic inflammation

What T helper cell and cytokines are involved with driving allergy?

Th₂ secretes IL-4, IL-5, IL-13 to activate eosinophils for allergy

What T helper cell and cytokines are involved with driving autoimmunity?

Th₁₇ secretes IL-17 and IL-22 activates neutrophils for autoimmunity

What does the presence of eosinophils vs. neutrophils in the lungs demonstrate?

• Presence of eosinophils in the lung suggests a Th2 allergic response

• Presence of neutrophils in the lung suggests a Th17 non-allergic response.

What is the difference between serum IgA1 and secretory IgA2

Serum IgA1 is pro-inflammatory and remains in the serum whereas secretory IgA2 is secreted by mucosa into the lumen and is non-inflammatory.

Define Asthma

A chronic inflammatory lung disease that leads to reversible narrowing of the airways, associated with increased airway hyperresponsiveness.

What are the two phases of asthma that are targeted by therapy?

1. Inflammation (preventers)

2. Smooth Muscle Contraction (relievers)

What is the immediate phase of asthma?

Eliciting agent like allergen triggers mast cells to release cytokines and histamine. This causes bronchospasm and smooth muscle constriction of the bronchioles.

What is the late phase of asthma?

Infiltration of Th2 cells and inflammatory eosinophils into the lamina propria of the bronchial walls. They release cytokines and cause damage to the epithelium and airway inflammation and hyper-reactivity.

What is the airway remodelling of asthma?

• Airway Smooth Muscle Hypertrophy and Hyperplasia

• Subepithelial Fibrosis (leads to permanent narrowing)

• Goblet Cell Hyperplasia and Metaplasia

• Epithelial Damage

What is the goal of relievers?prevent

B2 agonists target acute asthma and open up the airways

What is the goal of preventors/controllers?

Glucocorticoids target chronic asthma and reduce inflammation.

How do muscarinic antagonists help in asthma?

Blocks vagal tone, thereby increasing bronchodilation and reducing mucous secretions

How do ICS help in asthma?

Reduced cytokine, COX-2, IgE synthesis. By reducing the production of these inflammatory cytokines, ICS reduces inflammation damaging the lungs.

Define COPD

Progressive, chronic, inflammatory lung disease with more permanent airflow obstruction than asthma, less reversibility and less normalisation of airflow obstruction

What is emphysema?

Dilation and destruction of air spaces, leading to the decreased passive recoil of lungs and hyperinflated lungs (greater expansion needed to achieve normal breathing)

How does chronic bronchitis relate to COPD?

Describes the narrowing of airway lumens and excess mucus production that leads to a productive cough in COPD.

What is the difference in inflammation bw Asthma and COPD

Asthma is caused by allergens and is eosinophilic, whereas COPD is caused by toxins or pollutants and is neutrophilic.

Therapy for COPD?

• Dilators for acute symptoms (SABAs, and SAMAntagonists)

• Controllers LABA & LAMA

What is the pathophysiology of Type II Diabetes?

Insulin resistance, causing the pancreas to produce insulin less effectively & progressive beta-cell dysfunction

What is Diabetic Ketoacidosis?

• no insulin to produce glucose for cells .

• body breaks down fats rapidly for energy instead

• lipolysis creates waste ketones. Ketones build up in the blood and turn it dangerously acidic

What is HbA1c?

HbA1c (glycated haemoglobin) is haemoglobin A, the main adult haemoglobin, that has had glucose attached to it. It is a measure of average blood glucose over roughly the previous 2-3 months.

What is a normal HbA1c and what is diagnostic of diabetes?

Normal: < 5.7%

Prediabetes: 5.7%-6.4%

Diabetes: > 6.5%

What are the thresholds for fasting glucose values?

normal: < 5.5 - 6.1 mmol/L

prediabetes: 6.1 - 6.9 mmol/L

diabetes: > 7.0 mmol/L on two separate tests

What are the thresholds for random blood glucose values?

normal: 3.0 - 7.7 mmol/L

prediabetes; 7.8 - 11.0 mmol/L

diabetes: > 11.1 mmol/L

What are the drugs we can use to treat Diabetes (6)?

• Insulin

• Metformin

• GLP-1 Agonists

• SGLT2 Inhibitors

• DPP4 Inhibitor

• Sulphonylurea

Metformin MOA

Metformin lowers blood glucose mainly by reducing glucose production by the liver and, to a lesser extent, by improving insulin sensitivity in muscle and fat. It doesn’t stimulate insulin secretion, which is why it rarely causes hypoglycaemia on its own.

GLP-1 Agonist (e.g. - semaglutide) MOA

Binds GLP-1 receptors on beta-cells to stimulate insulin secretion. It amplifies glucose-sensing signal rather than bypassing it (as sulfonylureas do), so the effect depends on glucose being elevated. Also increases satiety and reduces hunger so people eat less and lose weight.

SGLT2 Inhibitor (e.g. - empagliflozin) MOA

Block the SGLT2 cotransporter in the PCT, to prevent the reabsorption of glucose, leading to more glucose being excreted out in the urine. Shouldn’t be used alongside sulfonylureas or insulin due to hypoglycaemia risk.

DPP4 Inhibitor (e.g. - sitagliptin) MOA

Blocks enzyme, dipeptidyl pepitdase 4, from breaking down incretins. Shouldn’t be used alongside sulfonylureas or insulin due to hypoglycaemia risk.

Sulfonylureas (e.g. - glipizide) MOA

Binding to K+ receptors on beta cells, stimulating the pancreatic beta cells to release insulin, regardless of the current glucose level. This makes them effective and cheap, but it is also why they cause hypoglycaemia and weight gain. They only work if the patient still has functioning beta cells.

How does ceftriaxone kill bacteria?

Cephalosporin - inhibits cross-linking of peptidoglycan in the cell wall.

Where does furosemide act?

NKCC2 in the thick ascending limb of the loop of Henle, where about 25% of filtered sodium is reabsorbed, making them the most powerful diuretics.

Which drug classes improve mortality in HFrEF?

ACE inhibitors (or ARBs/ARNI), β-blockers such as bisoprolol, mineralocorticoid antagonists and SGLT2 inhibitors all improve survival in HFrEF.

Preload

The amount of blood in the ventricles at the end of diastole (just before the heart contracts), which stretches the cardiac muscle fibers.

Afterload

The resistance or pressure that the ventricles must overcome to open the semilunar valves and push blood out into the systemic or pulmonary circulation