Cellulitis, Epistaxis, Mononucleosis, and Anemia Notes PDF

Cellulitis: Detailed Notes Overview: Definition: Cellulitis is an infection of the skin and the soft tissues beneath it. Function of Skin: The skin acts as a physical barrier between the environment and underlying soft tissues. Pathophysiology: Cellulitis occurs when ba...

Cellulitis: Detailed Notes Overview: Definition: Cellulitis is an infection of the skin and the soft tissues beneath it. Function of Skin: The skin acts as a physical barrier between the environment and underlying soft tissues. Pathophysiology: Cellulitis occurs when bacteria enter through a breach in the skin barrier. Common Entry Points: Skin trauma (e.g., cuts, abrasions) Eczema Fungal nail infections Ulcers Presentation Skin Changes: o Erythema: Red discoloration of the skin. o Temperature: Warm or hot to touch. o Texture: Skin may appear tense and thickened. o Oedematous: Swelling in the affected area. o Bullae: Presence of fluid-filled blisters. o Golden-yellow Crust: Indicates a possible Staphylococcus aureus infection. Systemic Symptoms: o Patients may exhibit signs of being systemically unwell. o Sepsis: Severe cases may progress to systemic infection, leading to sepsis. Causes of Cellulitis Most Common Causative Bacteria: o Staphylococcus aureus o Group A Streptococcus (e.g., Streptococcus pyogenes) o Group C Streptococcus (e.g., Streptococcus dysgalactiae) Special Consideration: o MRSA (Methicillin-resistant Staphylococcus aureus) should be considered, especially in patients with repeated hospital admissions or previous antibiotic use. Eron Classification: Assessing Severity Class 1: No systemic toxicity or comorbidity. Class 2: Presence of systemic toxicity or underlying comorbidity. Class 3: Significant systemic toxicity or significant comorbidity. Class 4: Presence of sepsis or life-threatening infection. Management Hospital Admission: o Indications: Required for Class 3 and Class 4 cellulitis. o Criteria: Consider admission for: ▪ Frail patients. ▪ Very young or immunocompromised individuals. ▪ Patients with facial, periorbital, or orbital cellulitis. Antibiotic Therapy: o First-Line Antibiotic: Flucloxacillin (effective against Staphylococcus aureus and other gram-positive cocci). ▪ Route of Administration: Can be administered orally or intravenously depending on severity. Epistaxis (Nosebleeds): Detailed Notes Overview: Definition: Epistaxis is the medical term for a nosebleed. Anatomy: o Primary Source of Bleeding: Kiesselbach’s plexus in Little’s area, located in the anterior part of the nasal cavity. This area is rich in blood vessels and prone to bleeding when the nasal mucosa is disrupted. o Exam Tip: Remember Little’s area as a likely source of bleeding, especially common in exam questions about epistaxis. Presentation Demographics: o Common in young children and older adults. Triggers: o Mechanical Causes: ▪ Nose picking (common in children).  ▪ Vigorous nose-blowing. ▪ Trauma (e.g., injury to the nose). o Medical and Environmental Triggers: ▪ Colds and sinusitis. ▪ Weather changes (affecting mucosal dryness and fragility). ▪ Coagulation Disorders: ▪ Examples include thrombocytopenia and Von Willebrand disease. ▪ Anticoagulant Medication: ▪ Aspirin, DOACs (Direct Oral Anticoagulants), or warfarin. ▪ Drug Use: Snorting substances such as cocaine. ▪ Tumors: Possibility of nasal tumors, like squamous cell carcinoma. Symptoms: o Swallowed Blood: Patients may present with hematemesis (vomiting blood) if blood is swallowed during the nosebleed. o Laterality: ▪ Bleeding is typically unilateral. ▪ Bilateral Bleeding may suggest posterior bleeding, which has a higher aspiration risk. Management Self-Resolution: o Most nosebleeds stop without medical intervention. o Recurrent or Significant Bleeds: Investigate potential underlying causes, such as thrombocytopenia or clotting disorders. Patient Advice for Nosebleed Management (often tested in exams): 1. Posture: Sit up and tilt the head forwards (prevents blood from flowing into the airway). 2. Nasal Pressure: Pinch the soft part of the nostrils together firmly for 10–15 minutes. 3. Spitting vs. Swallowing: Instruct patients to spit out any blood in the mouth rather than swallowing it to avoid nausea and vomiting. Indications for Hospital Admission: o Persistent bleeding despite 10–15 minutes of compression. o Severe or bilateral nosebleeds. o Haemodynamic instability. Hospital Treatment Options: o Nasal Packing: ▪ Can involve nasal tampons or inflatable packs to stop bleeding. o Nasal Cautery: ▪ Silver nitrate sticks are used to cauterize the bleeding vessels. Post-Treatment Care: o Naseptin Nasal Cream:  ▪ Contains chlorhexidine and neomycin. Applied four times daily for 10 days to reduce crusting, inflammation, and potential infection. ▪ Contraindication: Do not use if the patient has a peanut or soya allergy. Detailed Notes on Infectious Mononucleosis (IM) 1. Overview of Infectious Mononucleosis (IM) Cause: Infectious mononucleosis is caused by the Epstein-Barr virus (EBV), commonly known as “glandular fever” or “mono.” Transmission: o Spread through saliva, often by kissing or sharing items like cups or toothbrushes. o EBV can be infectious weeks before symptoms appear and intermittently for the patient’s lifetime. Population Affected: o Most people contract EBV in childhood, often with few symptoms. o When infection occurs in adolescents or young adults, it results in more symptomatic disease (IM). 2. Key Features Common Symptoms: o Fever o Sore Throat o Fatigue (can be prolonged even after the infection clears) o Lymphadenopathy: Swollen lymph nodes, often in the neck o Tonsillar Enlargement: Red and swollen tonsils, sometimes with a white or yellow coating o Splenomegaly: Enlarged spleen, with a risk of rupture in severe cases Maculopapular Rash: o A distinctive itchy rash can develop in patients who take amoxicillin or cephalosporins during IM. It is important to recognize this as an EBV reaction to avoid unnecessary antibiotics. 3. Diagnosis of Infectious Mononucleosis Heterophile Antibodies: o Purpose: These antibodies are non-specific but help confirm IM when EBV- specific tests are unavailable. o Tests for Heterophile Antibodies:  ▪ Monospot Test: Uses horse red blood cells that react with heterophile antibodies in the patient’s blood. ▪ Paul-Bunnell Test: Similar to the Monospot but uses sheep red blood cells. ▪ Limitations: ▪ Specificity: High specificity (almost 100%) for IM. ▪ Sensitivity: Moderate sensitivity (70-80%) because not all IM cases produce heterophile antibodies, and it may take up to 6 weeks post-infection to develop them. EBV-Specific Antibody Tests: o These tests detect antibodies specific to EBV’s viral capsid antigen (VCA): ▪ IgM: Indicates an acute infection (early rise in response). ▪ IgG: Suggests immunity and persists long after infection. 4. Management and Prognosis Self-Limiting Condition: o IM is typically self-resolving; acute symptoms last about 2-3 weeks, but fatigue may linger for months. Lifestyle Recommendations: o Avoid Alcohol: Due to EBV’s impact on liver function, patients are advised against consuming alcohol. o Avoid Contact Sports: Risk of splenic rupture means avoiding contact or high- impact activities. Splenic rupture is rare but requires emergency intervention if it occurs. General Advice: o Rest, hydration, and supportive care to manage symptoms are typically recommended. 5. Complications of Infectious Mononucleosis Splenic Rupture: Can lead to emergency situations requiring surgery. Renal Complications: o Glomerulonephritis: Kidney inflammation that may affect filtration function. Blood-Related Complications: o Haemolytic Anaemia: Destruction of red blood cells. o Thrombocytopenia: Reduced platelet count, which can affect blood clotting. Chronic Fatigue: Prolonged fatigue post-infection is a common issue. Associated Cancers: o EBV infection is linked to certain cancers, most notably Burkitt’s lymphoma. Iron Deficiency and Iron Deficiency Anaemia: Detailed Notes Overview: Iron’s Role: Iron is an essential component of haemoglobin. Iron Deficiency: Leads to anaemia characterized by microcytic hypochromic anaemia. o Microcytic: Red blood cells are smaller than normal, indicated by a low mean cell volume (MCV). o Hypochromic: Red blood cells appear pale due to reduced haemoglobin concentration. Causes of Iron Deficiency 1. Insufficient Dietary Iron: o Common in restrictive diets lacking adequate iron sources. 2. Reduced Iron Absorption: o Conditions such as coeliac disease reduce iron absorption in the gut. 3. Increased Iron Requirements: o Pregnancy and periods of growth increase the body’s need for iron. 4. Blood Loss: o Most Common Cause in Adults: Blood loss, particularly from the gastrointestinal (GI) tract. ▪ Menstruating Women: Menorrhagia (heavy periods) is a common cause. ▪ Non-menstruating Women and Men: GI tract bleeding is often the source. ▪ Sources of GI Bleeding: ▪ Cancer (e.g., stomach or bowel cancer) ▪ Oesophagitis and gastritis ▪ Peptic Ulcers ▪ Inflammatory Bowel Disease ▪ Angiodysplasia (abnormal blood vessels in the GI wall) 5. Dietary Insufficiency in Children: o High growth demands often exceed dietary iron intake. o Pica (e.g., eating non-food items like soil) may be a sign of iron deficiency in children. 6. Absorption Mechanism: o Absorption Site: Iron is absorbed primarily in the duodenum and jejunum. o Stomach Acid: Iron is absorbed in its soluble ferrous (Fe2+) form. Stomach acid helps maintain this form, but if acid is low (e.g., with proton pump inhibitors like omeprazole), iron converts to the insoluble ferric (Fe3+) form, hindering absorption. o Intestinal Inflammation: Conditions like coeliac disease or Crohn’s disease in the duodenum or jejunum further impair iron absorption. Testing for Iron Levels 1. Key Proteins and Markers: o Transferrin: A protein that binds and transports iron in the blood. o Total Iron-Binding Capacity (TIBC): Reflects the amount of transferrin available to bind iron. o Transferrin Saturation: Percentage of transferrin bound with iron. ▪ Formula: Transferrin saturation = serum iron / total iron-binding capacity. o Ferritin: A protein that stores iron within cells and acts as an acute-phase protein. ▪ Low Ferritin: Highly indicative of iron deficiency. ▪ High Ferritin: Could indicate inflammation, liver disease, iron supplements, or haemochromatosis. 2. Serum Iron: o Variability: Serum iron levels fluctuate throughout the day and rise after meals rich in iron, so it is not highly reliable as a standalone marker. 3. Marker Interpretations: o Iron Deficiency: TIBC and transferrin levels increase, transferrin saturation decreases. o Iron Overload: High serum iron, transferrin saturation, and ferritin, with low TIBC. 4. Normal Ranges: o Serum Ferritin: 41 – 400 µg/L o Serum Iron: 12 – 30 µmol/L o Total Iron-Binding Capacity: 45 – 80 µmol/L o Transferrin Saturation: 15 – 50% 5. Conditions Causing Iron Overload: o Haemochromatosis o Iron Supplements o Acute Liver Damage: Due to high iron stores in the liver. Management of Iron Deficiency Anaemia 1. Investigation of Underlying Causes: o New cases of iron deficiency in adults without clear causes (e.g., heavy menstruation or pregnancy) warrant further investigation. o Procedures: Colonoscopy and oesophagogastroduodenoscopy (OGD) are used to rule out malignancies. 2. Treatment Options: o Oral Iron Supplements: ▪ Common types include ferrous sulphate and ferrous fumarate. ▪ Efficacy: Typically results in a haemoglobin increase of around 20 g/L within the first month.  ▪ Side Effects: Can cause constipation and black stools. ▪ Prophylaxis: May be recommended in cases of recurrent deficiency. o Iron Infusion: ▪ IV Iron (e.g., CosmoFer) provides a rapid increase in iron levels. ▪ Risks: Potential for allergic reactions and anaphylaxis. ▪ Contraindications: Avoid during active infections to prevent “feeding” pathogens with iron. o Blood Transfusion: ▪ Reserved for severe cases of anaemia where immediate restoration of haemoglobin is necessary. Detailed Notes on Venous Thromboembolism (VTE) Overview Venous thromboembolism (VTE) includes: Deep Vein Thrombosis (DVT): Thrombus forms in deep veins, usually in the legs. Pulmonary Embolism (PE): A thrombus travels from a vein to the lungs, blocking pulmonary arteries and straining the right heart. If a patient has a septal heart defect, the thrombus can enter systemic circulation, potentially causing a stroke if it reaches the brain. Risk Factors for VTE Immobility (e.g., bed rest, long-haul flights) Recent surgery Pregnancy Hormone therapy (e.g., estrogen-based contraceptives or hormone replacement therapy) Malignancy Polycythaemia (high red blood cell count) Systemic lupus erythematosus Thrombophilias (e.g., antiphospholipid syndrome, Factor V Leiden) Note: For exams, inquire about VTE risk factors in patients with symptoms indicative of DVT or PE. Thrombophilias (Conditions Increasing Clotting Tendency)  Antiphospholipid syndrome (associated with recurrent miscarriage) Factor V Leiden mutation Antithrombin deficiency Protein C or S deficiency Hyperhomocysteinaemia Prothrombin gene variant Activated protein C resistance VTE Prophylaxis in Hospitalized Patients Prophylaxis: Low molecular weight heparin (LMWH) like enoxaparin is typically administered unless contraindicated. Anti-embolic compression stockings: Avoid in patients with peripheral arterial disease. DVT Presentation and Examination DVTs are often unilateral and present with: Calf or leg swelling Dilated superficial veins Calf tenderness (especially over deep veins) Oedema Color changes in the leg Measure calf circumference 10 cm below the tibial tuberosity; a >3 cm difference from the other leg suggests DVT. Wells Score for DVT The Wells score assesses the likelihood of DVT or PE based on risk factors and clinical findings. Use it to guide further testing: Likely DVT: Perform a leg vein ultrasound. Unlikely DVT: Perform a D-dimer test; if positive, follow with a leg vein ultrasound. Diagnostic Investigations  1. D-Dimer: High sensitivity but low specificity for VTE; it is often elevated in conditions like: o Pneumonia o Malignancy o Heart failure o Surgery o Pregnancy 2. Leg Vein Ultrasound: Primary diagnostic tool for DVT. Repeat ultrasound after 6-8 days if the initial scan is negative but D-dimer is positive. 3. CT Pulmonary Angiogram (CTPA): First-line imaging for PE, often used with a high Wells score for PE. Initial Management of Suspected VTE Anticoagulation: Start treatment-dose apixaban or rivaroxaban, or LMWH if oral anticoagulants are unsuitable. Catheter-Directed Thrombolysis: Considered for symptomatic iliofemoral DVT lasting under 14 days. Long-Term Anticoagulation Direct-acting Oral Anticoagulants (DOACs): First-line options include apixaban, rivaroxaban, edoxaban, and dabigatran. o Contraindications: Severe renal impairment, antiphospholipid syndrome, and pregnancy. Warfarin: Preferred in antiphospholipid syndrome, with a target INR of 2-3. LMWH: Preferred in pregnancy. Duration of Anticoagulation: 3 months for VTE with a reversible cause, then reassess. 3-6 months for active cancer, then reassess. Long-term for unprovoked VTE, recurrent VTE, or irreversible underlying conditions (e.g., thrombophilia). Inferior Vena Cava (IVC) Filter Used for patients unable to tolerate anticoagulation or with recurrent PE despite anticoagulation. It acts as a filter in the IVC to catch clots traveling from lower body veins toward the lungs. Investigating Unprovoked DVT For a first, unexplained VTE: Cancer Screening: Review history, baseline blood tests, and physical examination for malignancy indicators. Thrombophilia Testing: Check for antiphospholipid syndrome if VTE is unprovoked and not continuing anticoagulation beyond 3-6 months; hereditary thrombophilias may be tested if a first-degree relative also has a VTE history. Detailed Notes on Vitamin B12 Deficiency and Pernicious Anaemia Overview Vitamin B12 deficiency primarily leads to macrocytic anaemia and can cause neurological symptoms due to its role in nerve function and red blood cell formation. Common causes of deficiency include: 1. Pernicious anaemia 2. Insufficient dietary intake of B12 (especially in vegans, as B12 is primarily found in animal products) 3. Medications (e.g., proton pump inhibitors and metformin), which reduce B12 absorption Pernicious Anaemia Pathophysiology Autoimmune Condition: Pernicious anaemia involves the production of autoantibodies that target either the stomach's parietal cells or intrinsic factor. Intrinsic Factor: This protein, produced by parietal cells, is crucial for vitamin B12 absorption in the distal ileum. Autoimmune Attack: In pernicious anaemia, antibodies against intrinsic factor or parietal cells lead to a lack of intrinsic factor, impairing B12 absorption and resulting in deficiency. Symptoms of Vitamin B12 Deficiency Anaemia: Macrocytic anaemia with fatigue, weakness, and pallor. Neurological Symptoms (specific to B12 deficiency): o Peripheral neuropathy: Numbness and paraesthesia (pins and needles)  o Loss of vibration sense and proprioception o Visual changes o Mood and cognitive changes (e.g., memory loss, mood swings) Note: Vitamin B12 deficiency is often considered in patients presenting with peripheral neuropathy, especially those reporting pins and needles. Diagnostic Autoantibodies for Pernicious Anaemia 1. Intrinsic factor antibodies: The first-line investigation for pernicious anaemia. 2. Gastric parietal cell antibodies: Less specific and helpful but may support the diagnosis if intrinsic factor antibodies are negative. Management of Vitamin B12 Deficiency The treatment regimen depends on the presence of neurological symptoms and the cause of the deficiency. 1. Initial Treatment with Intramuscular Hydroxocobalamin: o No neurological symptoms: 3 times weekly injections for two weeks. o Neurological symptoms: Injections on alternate days until no further improvement is observed. 2. Maintenance Therapy: o Pernicious anaemia: Lifelong maintenance with 2-3 monthly injections. o Diet-related deficiency: Oral cyanocobalamin or twice-yearly intramuscular hydroxocobalamin injections. Essential Consideration in Combined Deficiencies When both B12 and folate deficiencies are present: Treat B12 deficiency first before correcting folate levels. Why?: Giving folic acid without addressing B12 deficiency can lead to subacute combined degeneration of the spinal cord, a serious neurological condition caused by spinal cord demyelination. This can result in severe neurological impairment. Key Points to Remember  Pernicious anaemia is diagnosed with intrinsic factor antibodies. B12 deficiency symptoms often include neurological issues; test B12 levels in patients with peripheral neuropathy. Always treat B12 deficiency before folate in cases of combined deficiencies to avoid severe neurological complications. Detailed Notes on Haemolytic Anaemia Overview Haemolytic anaemia occurs when red blood cells (RBCs) are destroyed faster than they are produced, leading to anaemia. It can be due to inherited conditions that make RBCs more fragile or acquired factors that actively destroy RBCs. Causes of Haemolytic Anaemia Inherited Causes 1. Hereditary spherocytosis: Autosomal dominant condition causing fragile, sphere- shaped RBCs, leading to splenic destruction. 2. Hereditary elliptocytosis: Similar to hereditary spherocytosis but with ellipse-shaped RBCs. 3. Thalassaemia: Genetic disorder resulting in abnormal haemoglobin production. 4. Sickle cell anaemia: RBCs become sickle-shaped, leading to haemolysis. 5. G6PD deficiency: X-linked condition causing RBC vulnerability to oxidative damage. Acquired Causes 1. Autoimmune haemolytic anaemia (AIHA): The immune system attacks RBCs. o Warm AIHA: Haemolysis at normal or above-normal temperatures. o Cold AIHA: Haemolysis at lower temperatures (under 10ºC), often linked to infections or autoimmune conditions. 2. Alloimmune haemolytic anaemia: Reaction to foreign RBCs (e.g., transfusion reactions, haemolytic disease of the newborn). 3. Paroxysmal nocturnal haemoglobinuria: Acquired mutation in haematopoietic stem cells, causing complement-mediated RBC destruction. 4. Microangiopathic haemolytic anaemia (MAHA): RBCs destroyed by clotting obstructions in small blood vessels, commonly associated with HUS, DIC, TTP, and cancer. 5. Prosthetic valve-related haemolysis: RBCs are mechanically damaged due to turbulent flow around heart valves. Key Features of Haemolytic Anaemia Anaemia: Reduced haemoglobin due to RBC destruction. Splenomegaly: Spleen becomes filled with destroyed RBCs. Jaundice: Resulting from bilirubin release during RBC destruction. Investigations for Haemolytic Anaemia 1. Full Blood Count (FBC): Shows normocytic anaemia. 2. Blood Film: o Schistocytes: RBC fragments, especially in microangiopathic haemolytic anaemia. o Spherocytes: Found in hereditary spherocytosis. o Heinz bodies: Found in G6PD deficiency. 3. Direct Coombs Test: Positive in autoimmune haemolytic anaemia. Specific Conditions 1. Hereditary Spherocytosis Features: Anaemia, jaundice, gallstones, splenomegaly. Diagnosis: High mean corpuscular haemoglobin concentration (MCHC), raised reticulocyte count, spherocytes on blood film. Management: Folate supplementation, blood transfusions, splenectomy if severe, and cholecystectomy if gallstones occur. 2. Hereditary Elliptocytosis Features and Management: Similar to hereditary spherocytosis but with elliptical RBCs. 3. G6PD Deficiency Triggers: Infections, certain drugs (e.g., ciprofloxacin, sulfonylureas), fava beans. Features: Jaundice, gallstones, anaemia, splenomegaly. Diagnosis: G6PD enzyme assay; Heinz bodies on blood film. Management: Avoid triggers and manage anaemia as needed. 4. Autoimmune Haemolytic Anaemia (AIHA)  Types: o Warm AIHA: Occurs at normal temperatures, often idiopathic. o Cold AIHA: Agglutination and haemolysis at low temperatures, associated with conditions like lymphoma and infections. Management: Blood transfusions, prednisolone, rituximab, splenectomy if severe. 5. Alloimmune Haemolytic Anaemia Types: o Haemolytic transfusion reaction: Reaction to transfused RBCs. o Haemolytic disease of the newborn: Maternal antibodies attack fetal RBCs in Rh-incompatible pregnancies. Management: Anti-D prophylaxis to prevent sensitisation in Rh-negative mothers. 6. Paroxysmal Nocturnal Haemoglobinuria Features: Red morning urine, anaemia, thrombosis, smooth muscle dystonia. Management: Eculizumab (a monoclonal antibody against C5) or bone marrow transplant if needed. 7. Microangiopathic Haemolytic Anaemia (MAHA) Associated Conditions: Haemolytic uraemic syndrome (HUS), disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), cancer, SLE. Blood Film Finding: Schistocytes. Management: Treat underlying cause, supportive care. 8. Prosthetic Valve-Related Haemolysis Features: Anaemia due to RBC damage from turbulent blood flow around the valve. Management: Monitoring, iron and folic acid supplements, blood transfusions if severe, and potential valve revision surgery if necessary. General Management of Haemolytic Anaemia 1. Identify and manage underlying cause. 2. Supportive Care: o Folate supplementation: To aid RBC production. o Blood transfusions: If severe anaemia. o Splenectomy: In cases of significant splenic sequestration or inherited conditions like hereditary spherocytosis. Detailed Notes on Thalassaemia Overview Thalassaemia is an inherited blood disorder caused by genetic defects in haemoglobin production. The defect can affect either the alpha or beta chains of haemoglobin, resulting in alpha-thalassaemia or beta-thalassaemia. Both types are autosomal recessive. The primary consequence is haemolytic anaemia, as fragile red blood cells (RBCs) break down easily, leading to various symptoms. Common Features of Thalassaemia Microcytic anaemia (low mean corpuscular volume, MCV) Fatigue and pallor Jaundice due to haemolysis Gallstones due to increased bilirubin from RBC breakdown Splenomegaly (enlarged spleen as it filters out destroyed RBCs) Poor growth and development in severe cases Investigations for Thalassaemia 1. Full Blood Count (FBC): o Microcytic anaemia (low MCV). 2. Ferritin: o Raised ferritin levels may indicate iron overload. 3. Haemoglobin Electrophoresis: o Diagnostic tool to identify abnormal haemoglobin chains. 4. DNA Testing: o Confirms genetic abnormalities. 5. Antenatal Screening: o All pregnant women in the UK are screened for thalassaemia. Iron Overload in Thalassaemia Iron overload occurs due to: Increased iron absorption in the gastrointestinal tract. Frequent blood transfusions (for severe cases). Complications of iron overload:  Liver cirrhosis Endocrine disorders (e.g., hypogonadism, hypothyroidism) Heart failure Diabetes Osteoporosis Management: Regular monitoring of serum ferritin levels. Iron chelation therapy to remove excess iron. Types of Thalassaemia 1. Alpha-Thalassaemia Genetics: Caused by mutations in the alpha-globin genes on chromosome 16. Severity: Varies based on the number of defective alpha genes: o Carrier: Asymptomatic. o Haemoglobin H Disease: Moderate anaemia. o Alpha Thalassaemia Major: Severe anaemia leading to intrauterine death. Management: Monitoring. Blood transfusions as required. Splenectomy may be considered. Bone marrow transplant can be curative. 2. Beta-Thalassaemia Genetics: Caused by mutations in the beta-globin gene on chromosome 11. Types: o Thalassaemia Minor (Trait): One normal and one abnormal gene; causes mild microcytic anaemia and usually only requires monitoring. o Thalassaemia Intermedia: Two abnormal beta genes (either two defective or one defective and one deletion gene); causes more significant anaemia, requiring monitoring, occasional transfusions, and potentially iron chelation. o Thalassaemia Major: Two deletion genes, resulting in no functioning beta- globin genes; presents in early childhood with severe anaemia and growth issues. Thalassaemia Major Features Severe anaemia, failure to thrive. Bone marrow expands to compensate for chronic anaemia, leading to skeletal changes:  o Frontal bossing (prominent forehead). o Enlarged maxilla (prominent cheekbones). o Depressed nasal bridge (flat nose). o Protruding upper teeth. Management for Beta-Thalassaemia Major: Regular blood transfusions. Iron chelation therapy to prevent iron overload. Splenectomy in cases with severe splenomegaly. Bone marrow transplant offers potential cure. Key Management Points Monitoring: Regular monitoring for anaemia, growth, and iron overload. Transfusions: Frequent transfusions in severe cases to manage anaemia. Iron Chelation: Essential to prevent complications from iron overload. Surgical Interventions: Splenectomy may be needed for severe splenomegaly, and cholecystectomy for gallstones. Curative Option: Bone marrow transplant is a curative option in some cases, particularly for severe forms like thalassaemia major. Detailed Notes on Sickle Cell Anaemia Overview Sickle cell anaemia is an autosomal recessive genetic disorder that causes red blood cells (RBCs) to become sickle or crescent-shaped due to the presence of abnormal haemoglobin S (HbS). The sickle shape makes RBCs more fragile, leading to haemolytic anaemia and various types of sickle cell crises. Pathophysiology Haemoglobin S (HbS): Replaces normal adult haemoglobin (HbA) in affected individuals. Autosomal Recessive Condition: Mutation affects the beta-globin gene on chromosome 11. Sickle Cell Trait: One abnormal copy (carrier, asymptomatic). Sickle Cell Disease: Two abnormal copies (affected, symptomatic). Patients with sickle-cell disease have RBCs that assume a rigid, sickle shape, which can occlude capillaries, leading to ischaemia and multiple complications. Relation to Malaria Selective Advantage: Individuals with sickle cell trait are more resistant to malaria, which explains the higher prevalence of the gene in regions historically affected by malaria (e.g., Africa, India, Caribbean). Screening Newborn Screening: Blood spot test at around 5 days of age. Antenatal Screening: Offered to pregnant women at high risk of carrying the sickle cell gene. Complications 1. Anaemia 2. Increased Infection Risk 3. Chronic Kidney Disease 4. Sickle Cell Crises (various types) 5. Acute Chest Syndrome 6. Stroke 7. Avascular Necrosis (particularly in large joints, e.g., hip) 8. Pulmonary Hypertension 9. Gallstones 10. Priapism (persistent, painful erections) Sickle Cell Crisis Sickle cell crisis refers to acute exacerbations of the disease, which can range from mild to life- threatening and may be triggered by dehydration, infection, stress, or cold weather. Management: o Supportive Care: Hospital admission, hydration (IV fluids), warmth, and pain management. o Avoid NSAIDs in renal impairment. Types of Sickle Cell Crisis 1. Vaso-occlusive Crisis (VOC): o Cause: Sickle cells obstruct capillaries, causing distal ischaemia. o Symptoms: Pain and swelling in hands, feet, chest, back, or other areas; fever may be present. o Priapism: Painful, prolonged erection due to blood trapping; treated as a urological emergency with aspiration. 2. Splenic Sequestration Crisis: o Cause: Sickle cells block blood flow in the spleen, causing splenomegaly, severe anaemia, and hypovolaemic shock. o Emergency: Managed with blood transfusions and fluid resuscitation. o Prevention: Splenectomy for recurrent cases to prevent future crises and reduce infection risk from hyposplenism. 3. Aplastic Crisis: o Cause: Temporary halt in RBC production, usually triggered by parvovirus B19 infection. o Symptoms: Severe anaemia. o Management: Supportive care and blood transfusions if required. Usually resolves in about a week. 4. Acute Chest Syndrome: o Cause: Vessels in the lungs clogged by sickled cells, often triggered by infection, fat embolism, or vaso-occlusion. o Symptoms: Fever, dyspnoea, chest pain, cough, and hypoxia; chest x-ray shows pulmonary infiltrates. o Emergency: High mortality rate; requires IV fluids, antibiotics or antivirals, analgesia, blood transfusions, and respiratory support (e.g., incentive spirometry, oxygen therapy, ventilation if needed). General Management of Sickle Cell Disease Avoid Crisis Triggers: Dehydration, stress, and infections. Vaccinations: Keep up-to-date. Antibiotic Prophylaxis: Typically with penicillin V to prevent infections. Hydroxycarbamide: Stimulates production of fetal haemoglobin (HbF), which does not sickle, reducing VOC frequency, improving anaemia, and potentially extending lifespan. Crizanlizumab: Monoclonal antibody that targets P-selectin to prevent RBC adherence to vessel walls, decreasing VOC frequency. Blood Transfusions: For severe anaemia. Bone Marrow Transplant: Can be curative but reserved for severe cases. Key Medications and Treatments 1. Hydroxycarbamide: Stimulates HbF, lowering VOC frequency and improving quality of life. 2. Crizanlizumab: Prevents RBC adherence to vessel walls, reducing crises. 3. Blood Transfusions: Essential for managing severe anaemia and certain crises. 4. Bone Marrow Transplant: Offers a potential cure in eligible patients. Detailed Notes on Hypertension 1. Definition and Diagnosis Diagnosis Criteria: o Clinic blood pressure (BP) above 140/90 mmHg requires confirmation with ambulatory or home BP readings. o Confirm hypertension if: ▪ Ambulatory or Home BP > 135/85 mmHg. NICE Recommendations: o Routine BP screening every 5 years, more frequent if borderline or diabetic. o Measure BP in both arms; if difference >15 mmHg, use the higher reading. Stages of Hypertension: o Stage 1: Clinic >140/90 mmHg, Confirmed >135/85 mmHg o Stage 2: Clinic >160/100 mmHg, Confirmed >150/95 mmHg o Stage 3: Clinic BP >180/120 mmHg 2. Causes of Hypertension Essential Hypertension: 90% of cases; no secondary cause identified. Secondary Causes (ROPED Mnemonic): o R: Renal disease (common, check for renal artery stenosis) o O: Obesity o P: Pregnancy-induced hypertension or pre-eclampsia o E: Endocrine causes (e.g., hyperaldosteronism/Conn’s syndrome) o D: Drugs (e.g., alcohol, NSAIDs, steroids, oestrogen, liquorice) 3. Complications of Hypertension Cardiovascular: o Ischaemic heart disease (angina, acute coronary syndrome) o Heart failure  o Peripheral arterial disease, aortic dissection, aneurysms Neurological: o Stroke (ischemic, intracranial hemorrhage) o Vascular dementia Kidney: o Hypertensive nephropathy Ophthalmic: o Hypertensive retinopathy Muscular: o Left ventricular hypertrophy (identified via echocardiogram or ECG) 4. End Organ Damage Assessment Tests Recommended by NICE: o Urinalysis: Urine albumin ratio, dipstick for proteinuria and hematuria o Blood Tests: HbA1c, renal function, lipids o Fundoscopy: To assess hypertensive retinopathy o ECG: To detect cardiac abnormalities (e.g., left ventricular hypertrophy) 5. QRISK Calculation Purpose: Estimates 10-year stroke or myocardial infarction risk. Recommendation: If QRISK >10%, initiate atorvastatin 20 mg at night. 6. Management of Hypertension Lifestyle Modifications: o Healthy diet, regular exercise, reduced salt, caffeine, and alcohol intake, smoking cessation. Medication (ABCD): o A: ACE Inhibitor (e.g., ramipril) or ARB (e.g., candesartan) if ACE not tolerated. o B: Beta Blocker (e.g., bisoprolol) as an additional agent. o C: Calcium Channel Blocker (e.g., amlodipine). o D: Thiazide-like Diuretic (e.g., indapamide). Stepwise Approach: o Step 1: Under 55 or type 2 diabetic: Start with A; over 55 or Black African: Start with C.  o Step 2: A + C or A + D or C + D. o Step 3: A + C + D. o Step 4: A + C + D + fourth agent based on potassium level. Step 4 Options Based on Potassium: o ≤4.5 mmol/L: Potassium-sparing diuretic (e.g., spironolactone). o >4.5 mmol/L: Alpha-blocker (e.g., doxazosin) or beta-blocker (e.g., atenolol). 7. Treatment Targets Under 80 years: Systolic 7.45: Alkalosis To determine the cause of acidosis or alkalosis, assess whether it is respiratory or metabolic. Respiratory Acidosis Mechanism: CO₂ creates acidity in blood by converting to carbonic acid (H₂CO₃). Indicators: Low pH with raised PaCO₂, signifying CO₂ retention. Acute vs. Chronic: o Acute: Bicarbonate does not rise quickly enough to compensate. o Chronic (e.g., COPD): Kidneys increase bicarbonate production to buffer CO₂, resulting in higher-than-normal bicarbonate even in acidosis. Bicarbonate Produced by kidneys as a buffer to neutralize acid in the blood. Raised bicarbonate indicates chronic CO₂ retention (e.g., chronic COPD), where kidneys have adapted by producing more bicarbonate. Respiratory Alkalosis Cause: Rapid breathing “blows off” too much CO₂. Indicators: High pH (alkalosis) with low PaCO₂. Common Scenarios: o Hyperventilation syndrome (e.g., anxiety) o Pulmonary embolism (PE) where hypoxia leads to increased breathing rate (distinguishable by low PaO₂ in PE vs. high PaO₂ in hyperventilation). Metabolic Disorders Metabolic Acidosis Indicators: Low pH and low bicarbonate. Causes: o Raised lactate: Anaerobic respiration (tissue hypoxia) o Raised ketones: Diabetic ketoacidosis o Increased H⁺ ions: Renal failure, type 1 renal tubular acidosis, rhabdomyolysis o Reduced bicarbonate: Diarrhea (loss of bicarbonate in stools), renal failure, type 2 renal tubular acidosis Metabolic Alkalosis Indicators: Raised pH and raised bicarbonate. Cause: Loss of hydrogen (H⁺) ions, commonly through: o Gastrointestinal tract: Vomiting (loss of stomach acid) o Kidneys: Elevated aldosterone increases H⁺ excretion Conditions with Elevated Aldosterone: o Conn’s syndrome (primary hyperaldosteronism) o Liver cirrhosis o Heart failure o Diuretics (loop and thiazide types) Asthma: Detailed Notes Overview of Asthma Definition: A chronic inflammatory disease of the airways, leading to variable airway obstruction. Mechanism: Airway smooth muscle is hypersensitive, causing bronchoconstriction (reversible with bronchodilators like salbutamol). Related Conditions: Often associated with other atopic conditions (eczema, hay fever, food allergies), with familial tendencies. Onset: Commonly in childhood but can develop at any age (adult-onset or occupational asthma). Presentation Episodic Symptoms: Symptoms have periods of exacerbation and remission, with diurnal variation (worse at night). Common Symptoms:  o Shortness of Breath o Chest Tightness o Dry Cough o Wheeze (expiratory and “polyphonic” in nature) Response to Bronchodilators: Improvement with bronchodilators supports an asthma diagnosis. Typical Triggers: Infections, nighttime, exercise, animals, cold/dusty air, strong emotions. Medications: Beta-blockers and NSAIDs can worsen asthma symptoms. Diagnosis and Investigations 1. Spirometry: o FEV1 Ratio: Less than 70% suggests obstructive pathology. o Reversibility Testing: >12% increase in FEV1 after bronchodilator supports asthma diagnosis. 2. Fractional Exhaled Nitric Oxide (FeNO): o Indicates airway inflammation. A level >40 ppb is a positive test. o Note: Smoking may reduce FeNO levels, affecting accuracy. 3. Peak Flow Variability: o Daily Peak Flow Diary: >20% variability supports asthma diagnosis. 4. Direct Bronchial Challenge Testing: o Methacholine or Histamine to induce bronchoconstriction. o PC20: 25, HR >110, unable to complete sentences. 3. Life-Threatening: o Peak flow 80% predicted o Stage 2 (Moderate): FEV1 50-79% predicted o Stage 3 (Severe): FEV1 30-49% predicted o Stage 4 (Very Severe): FEV1 < 30% predicted Additional Investigations: o BMI: Baseline measurement, as weight loss occurs in severe disease. o Chest X-Ray: Exclude other pathology, such as lung cancer. o FBC: To detect polycythaemia (raised Hb due to chronic hypoxia), anemia, or infection. o Sputum Culture: Identify chronic infections like Pseudomonas. o ECG/Echo: Assess for heart failure or cor pulmonale. o CT Thorax: To rule out fibrosis, cancer, or bronchiectasis.  o Alpha-1 Antitrypsin: Screen for deficiency in younger or non-smokers. o Transfer Factor for CO (TLCO): Tests gas diffusion (reduced in COPD). Long-Term Management 1. Lifestyle Modifications: o Smoking Cessation: Essential for slowing disease progression. o Vaccinations: Pneumococcal and annual influenza vaccines. o Pulmonary Rehabilitation: Multidisciplinary approach, including physical training and education. 2. Pharmacological Treatment (NICE 2019 Guidelines): o Initial: ▪ SABA (e.g., salbutamol) or SAMA (e.g., ipratropium) for symptom relief. o Second Line: ▪ No Asthmatic Features: LABA + LAMA combination (e.g., Anoro Ellipta, Ultibro Breezhaler). ▪ Asthmatic Features: LABA + ICS combination (e.g., Fostair, Symbicort). o Final Step: ▪ Triple Therapy: LABA + LAMA + ICS (e.g., Trimbow, Trelegy Ellipta). 3. Additional Treatments for Severe Disease: o Nebulisers: Salbutamol or ipratropium. o Oral Theophylline: For bronchodilation. o Mucolytics: e.g., carbocisteine to reduce sputum viscosity. o Prophylactic Antibiotics: e.g., azithromycin for frequent exacerbations. o Oral Corticosteroids: e.g., prednisolone for acute exacerbations. o Oxygen Therapy: For chronic hypoxia (if oxygen saturation < 92%). o Surgery: Lung volume reduction or lung transplant. o Palliative Care: Includes opiates for severe breathlessness. 4. Monitoring with Azithromycin: Regular ECG and liver function tests are required due to potential side effects. Cor Pulmonale Definition: Right-sided heart failure secondary to chronic lung disease (most commonly COPD). Mechanism: Increased pressure in pulmonary arteries causes right ventricular strain and back-pressure into systemic veins. Causes: COPD, pulmonary embolism, interstitial lung disease, cystic fibrosis, primary pulmonary hypertension. Signs: o Hypoxia and Cyanosis  o Raised JVP o Peripheral Oedema o Parasternal Heave and Loud Second Heart Sound o Tricuspid Regurgitation Murmur (e.g., pan-systolic) Management: o Symptomatic treatment (e.g., diuretics). o Long-Term Oxygen Therapy. o Poor Prognosis unless reversible cause is found. Acute Exacerbation of COPD Symptoms: Rapid worsening of cough, dyspnoea, increased sputum production, and wheezing. Common Triggers: Viral or bacterial infections. Investigations During Exacerbation ABG: Shows respiratory acidosis (low pH, high pCO2, low pO2). Other Tests: Chest x-ray (pneumonia), ECG (heart strain), FBC (infection), U&E (electrolytes), sputum culture, blood cultures for sepsis. Oxygen Therapy in COPD Exacerbation Target O2 Saturations: 88-92% for COPD patients at risk of CO2 retention. Venturi Masks: Deliver specific oxygen concentrations (24-60%). Management of Acute Exacerbation 1. First-Line Treatment: o Inhalers or Nebulisers: Salbutamol and ipratropium. o Steroids: Prednisolone 30 mg once daily for 5 days. o Antibiotics: If infection is suspected. 2. Severe Cases: o IV Aminophylline o Non-Invasive Ventilation (NIV): If respiratory acidosis is present and patient meets criteria. o Intubation: For life-threatening cases. 3. Respiratory Stimulant: Doxapram may be used if NIV/intubation is not appropriate. Non-Invasive Ventilation (NIV)  Definition: A face or nasal mask delivers high-pressure air to assist ventilation. Indications: Respiratory acidosis (pH < 7.35, PaCO2 > 6) unresponsive to other treatments. Mechanism: o IPAP (Inspiratory Positive Airway Pressure): Assists inspiration. o EPAP (Expiratory Positive Airway Pressure): Prevents airway collapse on expiration. Monitoring: Adjust IPAP based on ABG results until acidosis resolves. Contraindications: Untreated pneumothorax, facial structural issues, GI complications. Detailed Notes on Pulmonary Hypertension (PH) Overview of Pulmonary Hypertension Definition: Pulmonary hypertension (PH) is an increased pressure in the pulmonary arteries, causing right heart strain as it attempts to pump blood through the lungs. Measurement: PH is diagnosed when mean pulmonary arterial pressure is over 20 mmHg. Pathophysiology: Elevated pulmonary artery pressure creates back pressure, leading to right heart failure and increased systemic venous pressure. Causes (Classifications of Pulmonary Hypertension) 1. Group 1: Idiopathic pulmonary hypertension or due to connective tissue diseases (e.g., systemic lupus erythematosus). 2. Group 2: Left heart failure (often secondary to myocardial infarction or systemic hypertension). 3. Group 3: Chronic lung disease, such as COPD or pulmonary fibrosis. 4. Group 4: Pulmonary vascular disease (e.g., chronic thromboembolic pulmonary hypertension from pulmonary embolism). 5. Group 5: Miscellaneous causes, including sarcoidosis, glycogen storage diseases, and haematological disorders. Signs and Symptoms Primary Symptom: Shortness of breath (dyspnea) Additional Symptoms: o Syncope (fainting episodes) o Tachycardia (increased heart rate) o Raised jugular venous pressure (JVP), indicating venous congestion  o Hepatomegaly (enlarged liver) due to right heart strain o Peripheral oedema (swelling in extremities) Investigations 1. ECG Findings: o P pulmonale: Peaked P waves, often indicating right atrial enlargement o Right Ventricular Hypertrophy: Tall R waves in leads V1 and V2, deep S waves in V5 and V6 o Right Axis Deviation o Right Bundle Branch Block: Evidence of right-sided conduction delay 2. Chest X-Ray: o Dilated Pulmonary Arteries: Widening of the central pulmonary arteries o Right Ventricular Hypertrophy: Enlarged right ventricle silhouette 3. Blood Tests: o NT-proBNP: Raised levels indicate right ventricular failure or strain. 4. Echocardiogram: o Used to estimate pulmonary artery pressure and assess right heart function. Management 1. Idiopathic Pulmonary Hypertension (poor prognosis if untreated, with mean survival of 2-3 years): o Calcium Channel Blockers: Help relax pulmonary vascular smooth muscle. o Intravenous Prostaglandins (e.g., epoprostenol): Vasodilation to reduce pulmonary pressures. o Endothelin Receptor Antagonists (e.g., macitentan): Reduce vasoconstriction. o Phosphodiesterase-5 Inhibitors (e.g., sildenafil): Promote vasodilation by enhancing nitric oxide effects. 2. Secondary Pulmonary Hypertension: o Treatment of Underlying Condition: For example, managing pulmonary embolism, COPD, or systemic lupus erythematosus. 3. Supportive Treatments: o Oxygen Therapy: For respiratory support in cases of hypoxia. o Diuretics: To manage fluid overload, particularly in right heart failure. o Arrhythmia Management: Addressing rhythm disturbances due to right heart strain. Detailed Notes on Pulmonary Embolism (PE) Overview of Pulmonary Embolism Definition: PE is a blood clot in the pulmonary arteries, typically originating from a deep vein thrombosis (DVT) that has traveled to the lungs. Mechanism: A thrombus (clot) blocks blood flow in the lungs, causing strain on the right side of the heart. Grouping: DVTs and PEs are collectively known as venous thromboembolism (VTE). Risk Factors 1. Immobility (e.g., prolonged bed rest, long-haul flights) 2. Recent Surgery 3. Pregnancy 4. Hormone Therapy with oestrogen (e.g., combined oral contraceptive pill, hormone replacement therapy) 5. Malignancy 6. Polycythaemia (high hemoglobin levels) 7. Systemic Lupus Erythematosus (SLE) 8. Thrombophilia (increased tendency for blood clotting) VTE Prophylaxis Risk Assessment: Conducted for all hospital admissions. Prophylactic Treatment: o Low Molecular Weight Heparin (LMWH): Given to high-risk patients (e.g., enoxaparin), unless contraindicated. o Anti-embolic Compression Stockings: Used unless contraindicated (e.g., in peripheral arterial disease). Presentation of Pulmonary Embolism Symptoms: o Shortness of breath o Cough, possibly with haemoptysis (coughing up blood) o Pleuritic chest pain (sharp pain on inspiration) o Hypoxia (low oxygen saturation) o Tachycardia (high heart rate) o Raised respiratory rate o Low-grade fever o Haemodynamic instability (hypotension)  Signs of DVT: o Unilateral leg swelling o Leg tenderness Diagnostic Tools 1. PERC Rule: Used to rule out PE when PE probability is estimated at less than 15%. If all PERC criteria are met, further investigation for PE may not be required. 2. Wells Score: Assesses probability of PE by considering risk factors and clinical findings. Determines next steps based on PE likelihood. Investigations 1. Chest X-ray (CXR): Typically normal but necessary to exclude other causes. 2. D-dimer: o Purpose: High sensitivity for VTE but low specificity. Used to rule out VTE in low-suspicion cases. o False Positives: Other causes of raised D-dimer include pneumonia, malignancy, heart failure, recent surgery, and pregnancy. 3. Imaging: o CT Pulmonary Angiogram (CTPA): ▪ First-line imaging choice for PE. ▪ Uses contrast to visualize clots in pulmonary arteries and assess for alternative diagnoses. o Ventilation-Perfusion (V/Q) Scans: ▪ Used in patients unsuitable for CTPA (e.g., with renal impairment, contrast allergy, or radiation risk). ▪ Types: ▪ Planar V/Q scan: Produces 2D images. ▪ V/Q SPECT: Produces more accurate 3D images. Arterial Blood Gas (ABG) Typical Finding: Respiratory alkalosis with low CO₂ due to increased respiratory rate from hypoxia. Comparison: Respiratory alkalosis can also result from hyperventilation syndrome, but PE usually presents with low pO₂. Management 1. Supportive Care: o Hospital admission if needed. o Supplemental oxygen as required. o Analgesia for pain management. o Continuous monitoring for potential deterioration. 2. Anticoagulation: o First-line Agents: Apixaban or rivaroxaban (per NICE 2020). o Alternative: LMWH, especially if delay in confirmatory scan. 3. Massive PE with Haemodynamic Compromise: o Treated with continuous unfractionated heparin infusion. o Thrombolysis: Used when benefits outweigh bleeding risks. ▪ Agents: Streptokinase, alteplase, tenecteplase. ▪ Methods: ▪ Intravenous: Through peripheral cannula. ▪ Catheter-directed: Delivered directly into pulmonary arteries using a central catheter. Long-Term Anticoagulation 1. Options: o DOACs: Apixaban, rivaroxaban, edoxaban, dabigatran (no monitoring required). o Warfarin: For patients with antiphospholipid syndrome; INR target between 2 and 3. o LMWH: Preferred for pregnancy. 2. Duration: o 3 months: If a reversible cause is identified, with a review afterward. o Beyond 3 months: For unprovoked PE, recurrent VTE, or irreversible causes (e.g., thrombophilia). o 3-6 months: For patients with active cancer, with a review afterward. Lung Cancer: Detailed Notes Overview Prevalence: Third most common cancer in the UK, after breast and prostate cancer. Main Cause: Smoking (accounts for around 80% of cases). Prevention: Approximately 80% of cases are preventable. Basic Anatomy of the Lungs Airway Structure: Air enters through the trachea, which splits into: o Right and left main bronchi → lobar bronchi → segmental bronchi → bronchioles → alveoli. Lobes: o Right lung: 3 lobes (upper, middle, lower). o Left lung: 2 lobes (upper, lower) due to the space occupied by the heart. Pleura: o Double-layered membrane with a small fluid amount (< 20ml) that reduces friction. o Pleural Cavity: Potential space with negative pressure, allowing lung expansion. o Pleural Effusion: Excess fluid in pleural cavity. o Pneumothorax: Air in pleural cavity. Histology of Lung Cancer 1. Types: o Small-Cell Lung Cancer (SCLC): ~20% of lung cancers; notable for containing neurosecretory granules, which release neuroendocrine hormones and contribute to paraneoplastic syndromes. o Non-Small-Cell Lung Cancer (NSCLC): ~80% of cases, further divided into: ▪ Adenocarcinoma: ~40% of cases. ▪ Squamous Cell Carcinoma: ~20% of cases. ▪ Large-Cell Carcinoma: ~10% of cases. ▪ Other Types: ~10% of cases. 2. Mesothelioma: o Definition: Cancer of the pleura, strongly linked to asbestos. o Latency: Can develop up to 45 years post-exposure. o Prognosis: Poor; chemotherapy may improve survival but is palliative. Clinical Presentation of Lung Cancer Key Symptoms: o Shortness of breath o Persistent cough o Haemoptysis (coughing blood) o Finger clubbing o Recurrent pneumonia o Weight loss o Lymphadenopathy: Often in supraclavicular nodes. Extrapulmonary Manifestations and Paraneoplastic Syndromes 1. Nerve Involvement: o Recurrent Laryngeal Nerve Palsy: Hoarse voice due to tumour compression. o Phrenic Nerve Palsy: Diaphragm weakness causing shortness of breath. 2. Superior Vena Cava Obstruction: o Signs: Facial swelling, dyspnea, distended neck veins. o Pemberton’s Sign: Facial congestion and cyanosis on raising hands. 3. Horner’s Syndrome: Due to a Pancoast tumour compressing the sympathetic ganglion. o Triad: Ptosis, anhidrosis, miosis. 4. Paraneoplastic Syndromes: o SIADH: Ectopic ADH secretion by SCLC → hyponatraemia. o Cushing’s Syndrome: Ectopic ACTH from SCLC. o Hypercalcaemia: Ectopic parathyroid hormone from squamous cell carcinoma. o Limbic Encephalitis: SCLC-induced antibodies attacking the brain, causing memory issues, hallucinations, and seizures. o Lambert-Eaton Syndrome: SCLC-induced antibodies affect voltage-gated calcium channels, leading to muscle weakness, ptosis, and autonomic symptoms. Referral Criteria (NICE Guidelines, 2021) 1. Immediate Chest X-Ray (within 2 weeks) for patients >40 with: o Clubbing o Supraclavicular or persistent abnormal cervical lymphadenopathy o Recurrent/persistent chest infections o Raised platelet count (thrombocytosis) o Chest signs of lung cancer 2. Consider Chest X-Ray for patients >40 with: o Two or more unexplained symptoms in non-smokers. o One or more unexplained symptoms in smokers or former smokers. o Unexplained Symptoms: Cough, shortness of breath, fatigue, chest pain, weight loss, appetite loss. Investigations 1. Chest X-Ray: First-line for suspected lung cancer. o Findings: Hilar enlargement, peripheral opacity, pleural effusion, lung collapse. 2. Staging CT Scan (Chest, Abdomen, Pelvis): o Purpose: To assess tumour spread, lymph node involvement, and metastases. o Contrast-enhanced for better tissue visualization.  3. PET-CT: o Uses radioactive glucose tracer to identify areas of increased metabolic activity (often indicates metastasis). 4. Bronchoscopy with Endobronchial Ultrasound (EBUS): o Allows tumour assessment and ultrasound-guided biopsy. 5. Histology: o Required for definitive diagnosis. o Can be obtained through bronchoscopy or percutaneous biopsy. Treatment Options 1. Surgery (first-line in early-stage NSCLC): o Suitable for isolated, resectable tumours. o Types of Surgery: ▪ Segmentectomy/Wedge Resection: Removal of a segment of lung. ▪ Lobectomy: Removal of one lobe (most common). ▪ Pneumonectomy: Removal of an entire lung. o Surgical Techniques: ▪ Thoracotomy: Open surgery with rib separation. ▪ Video-Assisted Thoracoscopic Surgery (VATS): Minimally invasive. ▪ Robotic Surgery: Precision technique. 2. Radiotherapy: Curative in early-stage NSCLC. 3. Chemotherapy: o Adjuvant Chemotherapy: Post-surgery or radiotherapy to improve outcomes. o Palliative Chemotherapy: Improves quality of life and survival in advanced cases. 4. Small Cell Lung Cancer (SCLC): o Primarily treated with chemotherapy and radiotherapy (poorer prognosis than NSCLC). 5. Endobronchial Treatments: o Stents or Debulking for palliative relief of airway obstruction. Chest Drains Purpose: Used post-thoracic surgery to remove air and fluid, allowing lung expansion. Mechanism: Placed underwater to prevent air reentry; bubbles allow air to escape while preventing backflow. Observation: The water in the chest drain swings with respiration due to pressure changes in the chest. Detailed Notes on Pleural Effusion Overview of Pleural Effusion Definition: A pleural effusion is a collection of fluid in the pleural space between the lungs and chest wall. Types: o Exudative Effusion: High protein content (> 30 g/L) due to inflammatory processes. o Transudative Effusion: Low protein content (< 30 g/L) due to non-inflammatory processes. Light’s Criteria for Exudative Effusions Used to determine if an effusion is exudative by evaluating protein and lactate dehydrogenase (LDH) levels: 1. Pleural fluid protein / serum protein > 0.5 2. Pleural fluid LDH / serum LDH > 0.6 3. Pleural fluid LDH > 2/3 of the upper limit of normal for serum LDH If one or more of these criteria are met, the effusion is likely exudative. Causes of Pleural Effusion 1. Exudative Causes (related to inflammation allowing proteins to leak into the pleural space): o Cancer (e.g., lung cancer, mesothelioma) o Infection (e.g., pneumonia, tuberculosis) o Rheumatoid Arthritis 2. Transudative Causes (due to fluid shift or imbalance without inflammation): o Congestive Cardiac Failure o Hypoalbuminaemia o Hypothyroidism o Meigs Syndrome: A triad of a benign ovarian tumour (usually fibroma), pleural effusion, and ascites. The effusion and ascites resolve with tumour removal. Presentation of Pleural Effusion Primary Symptom: Shortness of breath.  Examination Findings: o Dullness to percussion over the effusion area o Reduced breath sounds o Tracheal deviation away from the effusion in cases of large effusions Investigations 1. Chest X-ray: o Blunting of the costophrenic angle o Fluid in lung fissures o Meniscus sign: Curving upwards where fluid meets the chest wall and mediastinum in large effusions o Tracheal and mediastinal deviation away from large effusions 2. Ultrasound and CT: o Detect smaller effusions, estimate the fluid volume, and identify underlying causes. 3. Pleural Fluid Analysis: o Sample obtained via aspiration or chest drain. o Tests include protein content, LDH, cell count, pH, glucose, and microbiology to determine the cause. Management of Pleural Effusion 1. Treating the Underlying Cause: The primary approach to managing pleural effusions. 2. Conservative Management: Small effusions often resolve with treatment of the underlying cause alone. 3. Interventions for Significant Effusions: o Pleural Aspiration: Temporary relief by aspirating fluid with a needle through the chest wall. Recurrence is possible, necessitating further drainage. o Chest Drain: Used for continuous drainage and to prevent recurrence in more persistent effusions. Empyema (Infected Pleural Effusion) Definition: An infected pleural effusion, often seen in patients with improving pneumonia but with a new or persistent fever. Diagnostic Indicators: o Pleural aspiration findings: Presence of pus, low pH, low glucose, and high LDH.  Treatment: Requires both chest drainage and antibiotic therapy to resolve the infection. Detailed Notes on Pneumothorax Overview of Pneumothorax Definition: Pneumothorax is when air enters the pleural space, causing lung separation from the chest wall. Types: o Spontaneous Pneumothorax: Occurs without an apparent cause, often in tall, thin young men during activity. o Traumatic Pneumothorax: Due to trauma to the chest. o Iatrogenic Pneumothorax: Caused by medical interventions, e.g., lung biopsy or central line insertion. o Secondary Pneumothorax: Resulting from underlying lung diseases, e.g., COPD, asthma, or infection. Causes of Pneumothorax 1. Spontaneous – no preceding trauma or intervention. 2. Trauma – physical injury to the chest. 3. Iatrogenic – due to medical procedures like lung biopsy or central line insertion. 4. Secondary to Lung Pathology – associated with underlying lung conditions such as: o Infection o Asthma o COPD Investigations 1. Chest X-ray (CXR): Primary investigation for diagnosing pneumothorax. o Findings: Visible area with no lung markings between the lung tissue and chest wall. o Size Measurement: As per BTS guidelines (2010), measure horizontally from the lung edge to the chest wall at the hilum. 2. CT Thorax: o More sensitive than CXR. o Used for small pneumothoraces not visible on CXR and for accurate measurement. Management of Pneumothorax Based on British Thoracic Society (BTS) guidelines 2023: 1. High-risk Patients: o Immediate chest drain required if there is haemodynamic compromise, bilateral pneumothorax, hypoxia, or underlying lung disease. 2. Lower-risk Patients: o Pneumothorax 2 cm: ▪ Procedure Avoidance Priority: Conservative management with regular outpatient follow-up. ▪ Rapid Symptom Relief: ▪ Outpatient Management: Pleural vent ambulatory device. ▪ Short-term Drainage: Needle aspiration or chest drain insertion. Pleural Vent Ambulatory Device Description: A catheter in the pleural space connected to a one-way valve device. Function: Allows air to exit but prevents re-entry. Use: Patients can manage pneumothorax as outpatients until resolved. Chest Drain Insertion Placement: In the "triangle of safety," which is bounded by: o 5th intercostal space (inferior nipple line), o Midaxillary line (lateral edge of latissimus dorsi), o Anterior axillary line (lateral edge of pectoralis major). Insertion Technique: Insert needle above the rib to avoid the neurovascular bundle. Chest Drain Management: o Underwater Seal: Prevents backflow of air, allowing air to escape. o Monitoring: Look for bubbling (air leak), swinging of water with respiration, and lung re-inflation on repeat CXR. o Common Issues: ▪ Blocked/kinked tube, ▪ Incorrect chest position, ▪ Disconnected from drain bottle. Complications: o Air Leaks: Persistent bubbling around the drain site, especially when coughing. o Surgical Emphysema: Air collecting in subcutaneous tissue. Surgical Management for Recurrent or Persistent Pneumothorax 1. Indications: Persistent pneumothorax, chest drain failure, or recurrent pneumothorax. 2. Surgical Options: o Video-Assisted Thoracoscopic Surgery (VATS): ▪ Pleurodesis: Causes pleural irritation to seal the space. ▪ Pleurectomy: Removal of pleura. o Types of Pleurodesis: ▪ Abrasive Pleurodesis: Physical irritation. ▪ Chemical Pleurodesis: Use of chemicals (e.g., talc powder). Tension Pneumothorax Definition: Life-threatening pneumothorax with a one-way valve effect, causing trapped air and rising intrathoracic pressure. Pathophysiology: o Air enters the pleural space on inspiration but cannot exit, increasing intrathoracic pressure. o Leads to mediastinal shift, vessel kinking, and cardiorespiratory arrest. Signs of Tension Pneumothorax Tracheal Deviation: Away from the affected side. Reduced Air Entry: On the affected side. Percussion Resonance: Increased on the affected side. Vital Signs: Tachycardia, hypotension. Management of Tension Pneumothorax Immediate Action: Insert a large bore cannula: o Traditional location: 2nd intercostal space, midclavicular line. o Alternative (ATLS 2018): 4th or 5th intercostal space, anterior to midaxillary line for adults (chest wall thickness considerations). Definitive Treatment: Chest drain once decompression has been achieved with a cannula. Detailed Notes on Tuberculosis (TB) 1. Overview of Tuberculosis (TB) Cause: Caused by Mycobacterium tuberculosis (M. tuberculosis), a slow-dividing bacillus (rod-shaped bacteria) with high oxygen needs. Characteristics: o Acid-Fast Bacilli: M. tuberculosis has a waxy cell wall, making it resistant to gram staining. It is identified as an “acid-fast” bacterium. o Ziehl-Neelsen Stain: This special stain turns TB bacteria bright red against a blue background, essential for identification. Multidrug-Resistant TB (MDR-TB): o Some TB strains resist multiple drugs, such as isoniazid and rifampicin, complicating treatment. 2. Disease Course Transmission: Primarily spread through inhaling respiratory droplets from an infected individual. Possible Outcomes after Exposure: o Immediate Clearance: The immune system clears the bacteria without illness. o Primary Active TB: Initial active infection soon after exposure. o Latent TB: Bacteria become encapsulated, stopping disease progression. No symptoms or contagion, but bacteria remain in the body. o Secondary (Reactivated) TB: Latent TB reactivates, usually due to immunosuppression, leading to active infection. Miliary TB: Severe form where TB spreads throughout the body, often in immunocompromised patients. Extrapulmonary TB: o TB can affect areas beyond the lungs, such as: ▪ Lymph nodes, pleura, CNS, pericardium, GI tract, genitourinary system, bones/joints, skin. o Cold Abscesses: Firm, painless abscesses commonly in the neck, lacking typical signs of inflammation. 3. Risk Factors Close Contact with TB: Higher risk for household members or those in close quarters with infected individuals. High-Prevalence Regions: Immigrants and those with family from high-TB-prevalence regions.  Immunocompromised Patients: Particularly those with HIV or on immunosuppressant medications. Socioeconomic Factors: Malnutrition, homelessness, drug use, smoking, and alcohol abuse increase vulnerability. 4. BCG Vaccine Type: Bacillus Calmette–Guérin (BCG) vaccine uses live attenuated Mycobacterium bovis. Function: Provides immunity against M. tuberculosis, especially effective for preventing severe TB forms, though less protective against pulmonary TB. Pre-Vaccination Testing: o Mantoux Test: Patients undergo this test, and only those with a negative result receive the vaccine. o Contraindications: Not given to immunosuppressed individuals or those with HIV due to live vaccine risks. Indications for Use: o Targeted at individuals with higher TB risk (e.g., from high-TB regions, close contact with TB cases, healthcare workers). 5. Clinical Presentation Pulmonary TB Symptoms: o Cough: Persistent and gradually worsening. o Haemoptysis: Coughing up blood. o Systemic Symptoms: Lethargy, fever, night sweats, weight loss. Lymphadenopathy: Enlarged lymph nodes. Erythema Nodosum: Painful, red nodules on the shins (sign of subcutaneous fat inflammation). Spinal TB (Pott’s Disease): Back pain in spinal cases. 6. Investigations for TB Diagnostic Challenges: o Slow-growing bacteria that don’t respond to traditional gram staining. o Require specialized Ziehl-Neelsen staining for detection. Tests for Immune Response (to detect exposure, latent or active TB): o Mantoux Test: Skin test using purified protein derivative (PPD) to detect immune response.  o Interferon-Gamma Release Assay (IGRA): Blood test to detect immune response to TB antigens, used in cases where Mantoux results are unclear. Tests for Active Disease: o Chest X-ray: Identifies characteristic lung changes. o Sputum Cultures: Confirms presence of TB bacteria, though growth is slow and can take several weeks. 1. Diagnostic Testing for Tuberculosis Mantoux Test o Procedure: Involves intradermal injection of tuberculin (TB proteins) on the forearm, creating a small raised bleb. o Reading the Test: After 72 hours, measure the induration (firm swelling) at the injection site. o Positive Result: An induration of ≥5mm is considered positive, indicating TB exposure or infection. Interferon-Gamma Release Assays (IGRA) o Mechanism: Mixes blood with TB antigens; sensitized white blood cells from prior TB exposure release interferon-gamma. o Interpretation: A positive result indicates prior contact with M. tuberculosis. Chest X-Ray Findings o Primary TB: May show patchy consolidation, pleural effusions, and hilar lymphadenopathy. o Reactivated TB: Displays patchy or nodular consolidation with cavitation, usually in the upper lung zones. o Miliary TB: Characterized by “millet seed” appearance—small, uniformly distributed nodules (1-3mm) across lung fields. Cultures o Collection: Ideally collected before initiating treatment to assess drug resistance. o Collection Methods: ▪ Sputum Cultures: Requires three separate samples. ▪ Blood Cultures: Special bottles for Mycobacterium blood cultures. ▪ Lymph Node Biopsy or Aspiration. o Special Techniques: Sputum induction (nebulized saline) or bronchoscopy with lavage if sputum production is low. Nucleic Acid Amplification Tests (NAAT) o Function: Detects TB DNA for quicker diagnosis than traditional culture. o Use Cases: Employed in high-risk patients (e.g., HIV positive, children under 16) and suspected drug-resistant cases. 2. Treatment of Tuberculosis Latent TB: o Options include:  ▪ Isoniazid and Rifampicin: Taken for 3 months. ▪ Isoniazid: Taken alone for 6 months. Active TB (RIPE Regimen) o Treatment course: RIPE mnemonic for drug combination: ▪ R – Rifampicin: 6 months ▪ I – Isoniazid: 6 months ▪ P – Pyrazinamide: 2 months ▪ E – Ethambutol: 2 months o Pyridoxine Supplement: Co-prescribed with isoniazid to prevent peripheral neuropathy (vitamin B6 is protective). 3. Additional Management Considerations Screening for Co-infections: HIV, hepatitis B, and hepatitis C testing are essential. Contact Tracing: Testing and managing close contacts to prevent further spread. Mandatory Reporting: Notify the UK Health Security Agency (UKHSA) for all suspected cases. Patient Isolation: Active TB patients are isolated to prevent airborne spread, typically in negative pressure rooms in hospital settings. 4. Side Effects of TB Treatment Rifampicin: o Causes red/orange discoloration of body fluids (e.g., urine, tears). o Potent cytochrome P450 enzyme inducer, reducing efficacy of drugs like the contraceptive pill. Isoniazid: o Causes peripheral neuropathy (prevented by co-administration of pyridoxine). Pyrazinamide: o Leads to hyperuricaemia, which can cause gout and kidney stones. Ethambutol: o Risk of visual disturbances, including color blindness and reduced visual acuity. Hepatotoxicity: Rifampicin, isoniazid, and pyrazinamide are associated with liver toxicity, requiring regular monitoring. Detailed Notes on Sarcoidosis Overview  Definition: Sarcoidosis is a chronic granulomatous disorder characterized by granulomas (inflammatory nodules filled with macrophages). Cause: The cause of granuloma formation is unknown. Presentation: Symptoms range from asymptomatic to severe or life-threatening. Sarcoidosis is often associated with respiratory symptoms but has multiple systemic manifestations. Epidemiology Most Commonly Affected: o Age groups 20-39 or around 60 o Women o Black ethnic origin Typical Exam Presentation: A young Black woman with a dry cough, shortness of breath, and erythema nodosum (red nodules on the shins). Key Skin Features 1. Erythema Nodosum: o Presents as tender, red, raised subcutaneous nodules on the shins. o Characteristic of sarcoidosis but not exclusive; other causes exist. o Lesions resolve over time and may appear as bruises. 2. Lupus Pernio: o Specific to Sarcoidosis: Distinguishing feature. o Presents as raised purple lesions, often on the cheeks and nose. Organs Affected by Sarcoidosis Sarcoidosis can impact nearly every organ, but the lungs are most commonly affected, with respiratory physicians typically managing the disease. 1. Lungs (in over 90% of cases): o Mediastinal lymphadenopathy o Pulmonary fibrosis o Pulmonary nodules 2. Systemic Symptoms: o Fever, fatigue, weight loss 3. Liver: o Liver nodules, cirrhosis, cholestasis 4. Eyes:  o Uveitis, conjunctivitis, optic neuritis 5. Heart: o Bundle branch block, heart block, myocardial muscle involvement 6. Kidneys: o Kidney stones (hypercalcaemia-induced), nephrocalcinosis, interstitial nephritis 7. Central Nervous System: o Nodules, pituitary involvement (e.g., diabetes insipidus), encephalopathy 8. Peripheral Nervous System: o Facial nerve palsy, mononeuritis multiplex 9. Bones: o Arthralgia, arthritis, myopathy Lofgren’s Syndrome Definition: A specific presentation of sarcoidosis with a classic triad: o Erythema nodosum o Bilateral hilar lymphadenopathy o Polyarthralgia (pain in multiple joints) Differential Diagnosis Key conditions to differentiate from sarcoidosis due to similar presentations: Tuberculosis Lymphoma Hypersensitivity Pneumonitis HIV Toxoplasmosis Histoplasmosis Investigations 1. Blood Tests: o Raised ACE (angiotensin-converting enzyme): Often used as a screening marker. o Raised Calcium (hypercalcaemia) 2. Imaging: o Chest X-Ray: Hilar lymphadenopathy o High-Resolution CT Scan: Hilar lymphadenopathy and pulmonary nodules o MRI: Central nervous system involvement  oPET Scan: Highlights areas of active inflammation 3. Histology: o Bronchoscopy with Ultrasound-Guided Biopsy of mediastinal lymph nodes. o Histological Findings: Non-caseating granulomas with epithelioid cells. 4. Other Tests: o U&Es: Kidney function o Urine Albumin-Creatinine Ratio: To check for proteinuria o Liver Function Tests (LFTs): Liver involvement o Ophthalmology Assessment: Eye involvement o ECG and Echocardiogram: Cardiac assessment o Ultrasound: Liver and kidney assessment Management 1. Conservative Management: o Considered for asymptomatic or mild cases. 2. Oral Steroids: o First-line treatment for 6-24 months if treatment is necessary. o Bisphosphonates recommended to protect against osteoporosis in long-term steroid use. 3. Methotrexate: o Second-line option when steroids are ineffective or not suitable. 4. Lung Transplant: o Rarely required, only in severe pulmonary disease. Prognosis Spontaneous Resolution: Occurs in about half of patients, typically within two years. Chronic Course: Some cases progress to pulmonary fibrosis and pulmonary hypertension. Mortality: Overall mortality is less than 10%. Coeliac Disease: Detailed Notes Overview Definition: An autoimmune condition triggered by ingestion of gluten, leading to small intestine inflammation and damage. Prevalence: Can develop at any age, often under-diagnosed.  Associations: Strongly linked with other autoimmune conditions, especially type 1 diabetes and autoimmune thyroid disease. o Screening: Routine testing for coeliac disease is recommended for all new cases of type 1 diabetes and autoimmune thyroid conditions, even without symptoms. Pathophysiology Autoimmune Mechanism: In response to gluten, the immune system produces autoantibodies that target epithelial cells in the small intestine, leading to inflammation. Related Autoantibodies: 1. Anti-tissue transglutaminase antibodies (anti-TTG) – primary test for diagnosis. 2. Anti-endomysial antibodies (anti-EMA) – used as a secondary test. 3. Anti-deamidated gliadin peptide antibodies (anti-DGP) – less commonly used. Affected Area: Primarily impacts the jejunum of the small intestine, leading to villous atrophy and malabsorption. Genetic Markers: Strong association with HLA-DQ2 and HLA-DQ8 genotypes. Clinical Presentation Common Symptoms: o Diarrhoea o Bloating o Fatigue o Weight loss o Mouth ulcers In Children: Failure to thrive, delayed growth. Skin Manifestation: Dermatitis herpetiformis – an itchy, blistering rash typically located on the abdomen. Anaemia: Secondary to malabsorption and deficiencies in iron, vitamin B12, and folate. Neurological Symptoms (rare): o Peripheral neuropathy o Cerebellar ataxia o Epilepsy Diagnosis 1. Gluten-Containing Diet Requirement: The patient must be actively consuming gluten during testing, as antibodies and biopsy findings may normalize on a gluten-free diet. 2. Blood Tests:  o First-Line Tests: ▪ Total Immunoglobulin A (IgA): Checks for IgA deficiency, which may affect antibody testing. ▪ Anti-tissue transglutaminase (anti-TTG): Main diagnostic test. o Second-Line Test (if results are ambiguous): ▪ Anti-endomysial antibodies (anti-EMA) o IgA Deficiency Consideration: In cases of IgA deficiency, the test can give a false negative. Here, use IgG versions of anti-TTG or anti-EMA antibodies. 3. Confirmatory Testing: o Endoscopy with Jejunal Biopsy: Performed by a gastroenterologist for definitive diagnosis. o Biopsy Findings: ▪ Crypt hyperplasia ▪ Villous atrophy Management Primary Management: Lifelong gluten-free diet, which should resolve symptoms and prevent relapse if adhered to. Dietitian Support: May be helpful to assist with diet planning and ensure nutritional adequacy. Monitoring: Coeliac antibodies can be used to assess compliance and disease activity. Complications of Non-Adherence to Gluten-Free Diet Nutritional Deficiencies: Due to chronic malabsorption. Anaemia: Resulting from deficiencies in iron, folate, and vitamin B12. Osteoporosis: Due to poor calcium and vitamin D absorption. Hyposplenism: Leads to increased susceptibility to infections, especially encapsulated bacteria like Streptococcus pneumoniae. Ulcerative Jejunitis: Inflammation and ulceration of the jejunum. Malignancies: o Enteropathy-Associated T-Cell Lymphoma (EATL): A rare but severe complication. o Non-Hodgkin Lymphoma o Small Bowel Adenocarcinoma Detailed Notes on Systemic Lupus Erythematosus (SLE) Overview  Systemic Lupus Erythematosus (SLE): An autoimmune inflammatory disorder affecting multiple organs and systems, classified as a connective tissue disorder. "Erythematosus": Refers to the characteristic red malar (butterfly-shaped) rash across the face. Epidemiology: o Primarily affects women. o More common in individuals of Asian, African, Caribbean, and Hispanic ethnicity. o Typically presents in young to middle-aged adults. Disease Course: Generally relapsing-remitting with symptom flares followed by periods of remission. Pathophysiology Anti-Nuclear Antibodies (ANA): SLE is characterized by the presence of autoantibodies, particularly ANA, which target nuclear proteins, leading to chronic inflammation across various organs and tissues. Clinical Presentation Non-Specific Symptoms: o Fatigue and weight loss o Arthralgia (joint pain) and non-erosive arthritis o Myalgia (muscle pain) and fever Characteristic Symptoms: o Photosensitive malar rash: Butterfly-shaped rash over the nose and cheeks, exacerbated by sunlight. o Raynaud’s phenomenon: Sensitivity to cold in fingers/toes. o Mouth ulcers and hair loss o Oedema (from nephritis) o Lymphadenopathy and splenomegaly System-Specific Symptoms: o Pulmonary: Shortness of breath, pleuritic chest pain o Cardiovascular: Pericarditis o Renal: Proteinuria, lupus nephritis o Neurological: Neuropsychiatric symptoms, e.g., psychosis, seizures Investigations 1. Blood Tests:  o Full Blood Count: May show anaemia, leucopenia (low WBC), or thrombocytopenia (low platelets). o Inflammatory Markers: Raised ESR and low C3/C4 levels during active disease. o Urine Analysis: Proteinuria, particularly in lupus nephritis. 2. Autoantibodies: o Anti-Nuclear Antibodies (ANA): Present in ~85% of SLE patients. o Anti-dsDNA: Highly specific to SLE; levels correlate with disease activity. o Extractable Nuclear Antigen (ENA) Panel: Identifies specific antibodies (Anti- Sm, Anti-Ro, Anti-La) that help confirm SLE. 3. Additional Tests: o Antiphospholipid Antibodies: Found in up to 40% of SLE patients, associated with increased risk of venous thromboembolism. o Renal Biopsy: Used for lupus nephritis evaluation and to assess treatment response. Diagnostic Criteria EULAR/ACR Criteria (2019): Combines clinical features and serological markers to diagnose SLE, requiring both clinical findings and positive autoantibodies. Complications 1. Cardiovascular: Leading cause of death in SLE, due to chronic inflammation and hypertension leading to coronary artery disease. 2. Infections: Increased risk due to immunosuppressive treatment and disease activity. 3. Blood Disorders: o Anaemia (of chronic disease, haemolytic anaemia). o Leucopenia and neutropenia. o Thrombocytopenia. 4. Lung and Heart Inflammation: o Pericarditis and pleuritis. o Interstitial lung disease leading to pulmonary fibrosis. 5. Kidney: o Lupus nephritis: Progressive inflammation, potentially leading to renal failure. 6. Neurological: o Neuropsychiatric SLE: Inflammation in CNS, causing optic neuritis, transverse myelitis, or psychosis. 7. Pregnancy-Related: o Recurrent miscarriage. o Increased risk of intrauterine growth restriction, pre-eclampsia, and pre-term labour.  8. Thromboembolic Events: o Venous thromboembolism, particularly with antiphospholipid syndrome secondary to SLE. Management General Principles: Manage symptoms, minimize flares, and prevent complications with minimal medications and side effects. Sun Protection: Essential due to photosensitive malar rash. 1. First-Line Treatments: o Hydroxychloroquine: Anti-inflammatory and immunosuppressant. o NSAIDs: For pain relief in arthritis and musculoskeletal symptoms. o Steroids: E.g., prednisolone for acute flares. 2. Advanced Treatment: o DMARDs (Disease-Modifying Anti-Rheumatic Drugs): ▪ Methotrexate, mycophenolate mofetil, or cyclophosphamide for refractory or severe cases. o Biologic Therapies: ▪ Rituximab: Targets CD20 protein on B cells. ▪ Belimumab: Targets B-cell activating factor to reduce B cell activity. B Cell and Immunoglobulin Deficiency: Detailed Notes Overview of B Cells and Immunoglobulin Deficiency B Cells Function: Responsible for producing antibodies, a critical component of the adaptive immune system. Deficiency in Immunoglobulins (Hypogammaglobulinemia): Caused by abnormal B cells, leading to decreased antibody levels, resulting in: o Increased susceptibility to recurrent infections, particularly of the respiratory tract. Types of Immunoglobulin Deficiencies 1. Selective Immunoglobulin A (IgA) Deficiency o Prevalence: Most common immunoglobulin deficiency. o Presentation: ▪ Low levels of IgA with normal levels of IgG and IgM. ▪ Often asymptomatic, with many patients undiagnosed.  ▪Some patients may experience recurrent mucous membrane infections (e.g., respiratory tract infections) and are at higher risk for autoimmune conditions. o Role of IgA: ▪ Found in secretions of mucous membranes (saliva, respiratory tract, GI tract, tears, and sweat). ▪ Provides protection against opportunistic infections at mucosal surfaces. o Clinical Note (TOM TIP): ▪ Coeliac Disease Testing: Total IgA levels are essential when testing for coeliac disease (e.g., anti-TTG and anti-EMA antibodies). In IgA deficiency, these tests may yield false negatives. Alternative tests: ▪ Use IgG versions of anti-TTG or anti-EMA antibodies. ▪ Proceed with endoscopy and biopsy for confirmation. 2. Common Variable Immunodeficiency (CVID) o Cause: Genetic mutations affecting B cell components. o Immunoglobulin Profile: ▪ Deficiency in IgG and IgA, sometimes also in IgM. o Clinical Presentation: ▪ Recurrent respiratory tract infections, often leading to chronic lung disease over time. ▪ Inability to develop immunity to infections or from vaccinations. ▪ Prone to other immune disorders (e.g., rheumatoid arthritis) and certain cancers (e.g., non-Hodgkin lymphoma). o Management: ▪ Regular immunoglobulin infusions to support immunity. ▪ Treatment of infections and complications as they arise. 3. X-linked Agammaglobulinemia (Bruton’s Agammaglobulinemia) o Genetics: X-linked recessive condition, often affecting males. o Pathophysiology: ▪ Causes abnormal B cell development, leading to a deficiency in all classes of immunoglobulins. o Clinical Manifestations: ▪ Similar to CVID, with susceptibility to recurrent infections and chronic health issues due to immunodeficiency. Detailed Notes on Peptic Ulcers Pathophysiology Peptic Ulcers involve ulceration in: o Stomach - termed gastric ulcer o Proximal duodenum - termed duodenal ulcer (more common) Mucosal Protection:  o The mucosa (inner lining) of the stomach and duodenum secretes mucus, which forms a protective barrier against stomach acid and digestive enzymes. o Bicarbonate is secreted into this mucus to help neutralize stomach acid. Risk of Ulceration: Occurs when: o Mucus barrier is disrupted o Stomach acid production increases Risk Factors Disruption of Mucus Barrier: o Helicobacter pylori (H. pylori) infection o Non-steroidal anti-inflammatory drugs (NSAIDs) Increased Stomach Acid: o Stress o Alcohol consumption o Caffeine o Smoking o Spicy foods Increased Risk of Bleeding from Peptic Ulcers: o NSAIDs o Aspirin o Anticoagulants (e.g., direct oral anticoagulants - DOACs) o Steroids o SSRI antidepressants Presentation Typical Symptoms: o Epigastric discomfort or pain o Nausea and vomiting o Dyspepsia (indigestion) Symptoms Differentiating Gastric vs. Duodenal Ulcers: o Gastric Ulcers: Pain worsens with eating; patients may lose weight due to avoiding meals. o Duodenal Ulcers: Pain improves immediately after eating, then recurs 2-3 hours post-meal; weight tends to remain stable or increase. Signs of Upper Gastrointestinal Bleeding: o Haematemesis (vomiting blood) o Coffee ground vomiting (vomiting of partially digested blood) o Melaena (black, tarry stools) o Fall in haemoglobin on full blood count Chronic Bleeding Effects:  o Can cause iron deficiency anaemia, presenting with: ▪ Low haemoglobin ▪ Low mean cell volume (MCV) ▪ Low ferritin Diagnosis Endoscopy: o Allows direct visualization of the ulcer. o A rapid urease test (CLO test) can be performed during endoscopy to detect H. pylori. o Biopsy may be taken to exclude malignancy. Management Core Treatments: o Stop NSAIDs to reduce risk of further mucosal damage. o Treat H. pylori infection if present (usually with antibiotics). o Proton pump inhibitors (PPIs) (e.g., lansoprazole, omeprazole) to reduce stomach acid. Follow-Up: o Repeat endoscopy (4-8 weeks after initial treatment) to confirm ulcer healing. Complications Bleeding: o Common and can be life-threatening if severe. Perforation: o Causes acute abdominal pain and peritonitis (inflammation of the abdominal lining). o Requires urgent surgical repair, usually performed laparoscopically. Gastric Outlet Obstruction: o Caused by scarring and strictures that narrow the stomach’s exit. o Symptoms: ▪ Early fullness after eating ▪ Upper abdominal discomfort ▪ Abdominal distention ▪ Vomiting after meals o Treatment options: ▪ Balloon dilatation during endoscopy  ▪ Surgery for severe cases Detailed Notes on Irritable Bowel Syndrome (IBS) Pathophysiology of IBS IBS is a functional disorder of the gastrointestinal (GI) system, meaning: o No identifiable structural or organic disease underlies symptoms. o Symptoms arise from abnormal gut function. o There is a disturbance of the gut-brain interaction, causing troublesome abdominal and intestinal symptoms. Prevalence: o Affects up to 20% of the population. o More common in women than in men. o Often affects younger adults. Symptoms of IBS Key Features (Mnemonic: IBS): o I - Intestinal discomfort: Abdominal pain or discomfort related to bowel activity. o B - Bowel habit abnormalities: Changes in frequency or consistency of bowel movements. o S - Stool abnormalities: Variability in stool form, including watery, loose, hard, or mucus-filled. Common Symptoms: o Abdominal pain o Diarrhoea o Constipation o Flu