NUR2500 Applied Pathophysiology and Clinical Pharmacology Final Exam Notes PDF

NUR2500 Applied Pathophysiology and Clinical Pharmacology Final Examination Notes Topics: 1. Endocrine (6-8 questions) 2. Excretory System Disorders (13-15 questions) 3. GI System Disorders (18-20 questions) 4. Neuro System Disorders (8-10...

NUR2500 Applied Pathophysiology and Clinical Pharmacology Final Examination Notes Topics: 1. Endocrine (6-8 questions) 2. Excretory System Disorders (13-15 questions) 3. GI System Disorders (18-20 questions) 4. Neuro System Disorders (8-10 questions) 5. Reproductive System Disorders (4-5 questions) Topic 1: Endocrine Features Hyperthyroidism Hypothyroidism Thyroid hormone levels High (T3/T4) Low (T3/T4) TSH levels Low High Metabolism Accelerated (fast metabolism) Slowed (slow metabolism) Heart rate Increased (tachycardia) Decreased (bradycardia) Body temperature Heat intolerance (feeling warm) Cold intolerance (feeling cold) Weight Weight loss Weight gain Energy levels Often hyperactive or anxious Fatigue and sluggishness Hyperthyroidism - Commonly caused by Graves’ Disease - Symptoms: - Fine/brittle hair loss - Increased perspiration - Exophthalmos (bulging eyes), especially in Graves' disease. - Goiter (enlarged thyroid). - Abnormal heart rhythms - Weight loss despite increased appetite. - Tremors (shaking hands). - Nervousness, anxiety, or irritability. - Heat intolerance (feeling warm or sweaty). - Increased sweating. - Fatigue, muscle weakness. - Sleep disturbances (difficulty sleeping). - Diarrhea or frequent bowel movements. - Goiter (enlarged thyroid). - Blood tests: - Low TSH (Thyroid Stimulating Hormone) levels - Elevated T3/T4 levels. Hypothyroidism - Symptoms: - Thinning hair/ hair loss - Loss of eyebrow hair - Puffy face - Dry and coarse skin - Carpal tunnel syndrome - Fatigue and weakness. - Weight gain, even with normal or decreased appetite. - Cold intolerance (feeling cold, especially in hands and feet). - Dry skin and hair, hair loss. - Constipation. - Depression or mood changes. - Slowed heart rate (bradycardia). - Puffy face and swollen extremities. - Hoarseness or deepening of the voice. - Non-pitting oedema (accumulation of glycosaminoglycans (GAGs)) - Myxedema (severe form of hypothyroidism, can cause swelling, particularly around the eyes). - Complication: - Myxedema coma - confusion, hypothermia, and bradycardia - Blood tests: - Elevated TSH (Thyroid Stimulating Hormone) levels - Low T3/T4 levels. - Most common cause with adequate iodine intake: Hashimoto's thyroiditis Graves’ Disease - Hypersecretion of TH - Exophthalmos - Autoimmune disease: - Body produces antibodies that activate TH-secreting cells by mimicking TSH Parathyroidism Hyperparathyroidism Hypoparathyroidism - Caused by tumour - Caused by gland trauma or removal - Bones soften and deform - Results in tetany, respiratory paralysis, and death if - Elevated Ca2+ depresses the untreated nervous system and - Hypocalcaemia contributes to formation of - Tetany kidney stones - Chvostek sign aka Weiss sign (Contraction of facial (hypercalcaemia) muscles after tapping a facial nerve) - Trousseau sign (Induction of carpal pedal spasm) - Paresthesias (fingertips/perioral) - Prolonged QT interval Thyroid Hormones - Plays a role in - Regulation of tissue growth - Development of skeletal and nervous systems - Reproductive capabilities - Consists of: - T3 - T4 - Calcitonin Growth Hormones Gigantism Acromegaly Dwarfism and Cretinism - Excess GH in - Excess GH in Dwarfism childhood adulthood - Deficiency of GH in childhood - Onset before the - Onset after closure of - Normal intelligence closure of epiphyseal epiphyseal growth growth plates plates Cretinism - Typically seen in - Decreased TH in childhood children - Severe iodine deficiency in pregnancy - Mental retardation (cognitive) - Thyroid dwarfism - Failure in developing skeletal, mental, sexual abilities (physical) - Type I Diabetes Mellitus Patients undergoing a prolonged exercise session to prevent hypoglycaemia - Increase carbohydrate intake and reduce pre-exercise bolus insulin. Type II Diabetes Mellitus Type II Diabetes Mellitus Risk Factors Age Physical inactivity Alcohol drinking Family history Social history Hypertension Race/Ethnicity – Among the ethnic groups, the hypertension level was highest in the Malays (28.0%), followed by Chinese (23.4%) and Indians (19.3. 7%). Pathophysiologic Diabetes inhibits all phases of wound healing: Correlation Between ○ Impairment of function of primary cells involved in healing Impaired Wound Neutrophils Healing and State Macrophages Fibroblasts ○ Function of cytokines and growth factors are impaired Diabetes leads to vascular complications: ○ Macrovascular complications ○ Microvascular complications Neuropathy contributes to poor wound healing Chronic hyperglycaemia and glycaemic variability oxidative stress and neuroinflammatory processes neuropathic syndromes Dulled perception of vibration, pain, and temperature Multifactorial Microangiopathy Advanced glycated end products (AGEs) - cell surface receptor called RAGE (receptor for AGE) neural inflammation, disrupts cellular signalling, and alters normal gene expression in the  peripheral nervous system Polyol pathway – glucose sorbitol fructose – increased oxygen reactive species, inflammation Immunity is impaired Neutrophil chemotaxis and adherence to vascular endothelium, phagocytosis, intracellular bactericidal activity, opsonization, and cell-mediated immunity - depressed in Diabetics with hyperglycaemia Vascular insufficiency local tissue ischaemia enhances the growth of microaerophilic and anaerobic organisms; there is depression of the oxygen-dependent bactericidal functions of leukocytes Sensory peripheral neuropathy Lab Investigations Diabetic Complications: - FBC – For diabetic foot infection - Microalbuminuria - Earliest detectable clinical sign of diabetic nephropathy - C-reactive protein (CRP) & Procalcitonin – For diabetic foot infection - Wound culture – for diabetic foot - Arterial Blood Gas – If DKA / HHNS is suspected - X-ray foot – to determine involvement of osteomyelitis - (Direct) Ophthalmoscopy – diabetic retinopathy - Diabetic retinopathy screening - diabetic retinopathy - Podiatry review – diabetic foot - Ankle-Brachial Index – determine atherosclerotic disease Diabetic Investigation Profile: - Fasting plasma glucose - Random plasma glucose - HbA1C Treatment Approaches 1. Glycaemic management with oral hypoglycaemic or Injectable insulin a. The target is A1C levels to be 2 episodes per year, related to anatomic, metabolic, functional or neurological disorders - Upper UTI: Above bladder - Lower UTI: Below bladder - Risk Factors - Female - Increasing age - Vesico-urethral reflux - Pregnancy - Diabetes Mellitus - Contraceptive devices - Congenital defects - Obstruction: Stones - Signs and Symptoms of UTI: - Dysuria - Urgency - Increased frequency - Suprapubic or low back pain - Fever - Objective signs (not required for uncomplicated UTI) - Bacteriuria (102 to ≥105 colony-forming units/mL) - Pyuria (WBC >10/mm3) AKI and CKD Acute Kidney Injury Chronic Kidney Disease - Is not a primary diagnosis but rather a The international guideline group Kidney Disease: syndrome Improving Global Outcomes (KDIGO) - It occurs on the background of other illness – AKI is defined when one of the following criteria is met: such as worsening heart failure or sepsis - Serum Creatinine rise by > 26μmol/L within 48 - Usually treating the primary problem will help hours - Kidney damage can occur long before we are - Serum creatinine rise 1.5 x from the reference aware it is happening value, which is known or presumed to have - Key is to recognise those at risk and intervene occurred within one week at the earliest opportunity throughout regular - Urine output is < 0.5ml/kg/hr for 6 consecutive monitoring and assessment hours AKI Stage Serum Creatinine Urine Output Stage 1 1.5-1.9 x baseline < 0.5ml/kg/hr 6-12 hrs Stage 2 2.0-2.9 x baseline < 0.5ml/kg/hr for >12 hrs Stage 3 3.0 x baseline < 0.3ml/kg/hr for 24rs AKI Risk Factors Age (above 75 years) Chronic Kidney Disease Cardiac Failure Atherosclerosis Liver Disease Diabetes Nephrotoxic medications Causes Pre-renal - Most common cause of AKI - Flow disruption to the kidney - For example: - Low blood pressure - Heart Failure - Low blood volume Intrinsic - Damage to the kidney itself - For example: - Glomerulonephritis - Acute tubular Necrosis Post-renal - A consequence of urinary tract obstruction - For example: - Renal calculi - Blocked catheter - Bladder tumours Assessment - Baseline U&E, FBC - Urinalysis - Cultures (if indicated) - ECG  - CXR / AXR (if indicated) - Renal USG Treatments - Treat the underlying cause - E.g. Relieve any obstruction - Indications for Renal Replacement Therapy - Hyperkalaemia - Acidosis - Uraemia - Fluid overload - Pulmonary oedema CKD ➔ Either kidney damage or ↓GFR of less than 60 mL/min/1.73m2 for at least 3 months ➔ Once the loss of nephrons reaches a certain point, the remaining nephrons begin a process of irreversible sclerosis that leads to a progressive ↓ in GFR Pathophysiology - GFR reduction occurs with nephron loss - Kidneys compensate until 75% to 80% of nephrons are damaged/nonfunctional Causes - Diabetes - Hypertension - Recurrent pyelonephritis - Glomerulonephritis - Polycystic kidney disease - Recurrent kidney stone disease - Urinary tract obstruction or dysfunction Stages of CKD Stage 1: Normal or ↑ GFR (>90) Stage 2: Mild ↓ in GFR (60-89) Stage 3a: Moderate ↓ in GFR (45-59) Stage 3b: Moderate ↓ in GFR (30-44) Stage 4: Severe ↓ in GFR (15-29) Stage 5: Kidney failure (GFR < 15 or dialysis) Unit: mL/min/1.73 m2 Clinical Manifestations - Electrolyte imbalances - Retained potassium, phosphorus, magnesium - Bone and mineral disorders - ↑ phosphorus and PTH causes altered bone/mineral metabolism; kidneys unable to reabsorb Ca - Malnutrition - ↓ intake from uremic syndrome, depression, dietary limitations, changes in taste, protein-energy wasting; negative nitrogen balance - Anaemia - Lack of erythropoietin; uremia shortens RBCs life; combination of worsening CKD, anaemia, and heart failure (cardiorenal anaemia syndrome) - Pain - Disease itself, treatment, comorbidities - Depression - Co-morbid conditions; disease itself; disruption of social  interactions and relationships Complications - Hypertension and cardiovascular disease - Hypervolemia, ↑ atherosclerotic process, ↑ RAAS and SNS activity - Uremic syndrome - Retention of metabolic wastes; impaired healing, pruritus; dermatitis, uremic frost - Metabolic acidosis - Retention of acidic waste products; kidneys lose ability to secrete H+ ions and make bicarbonate Managements Hypertension and cardiovascular disease ○ ACEI/ARB/Statins Fluid and electrolyte imbalances ○ If edema/CCF/HTN: may need 2g/day Na restriction ○ Mild hyperkalemia (< 6 mmol/L): ↓ K intake, correct metabolic acidosis ○ Hyperkalemia (> 6 mmol/L): IV calcium gluconate, D5W and insulin; oral/rectal sodium polystyrene sulfonate Bone and mineral disorders ○ Hypocalcemia: calcium carbonate, calcium acetate, lanthanum carbonate ○ Vitamin D: for deficiency and suppress PTH ○ Calcimimetics: suppress PTH Malnutrition ○ Calories, vitamins, calcium ↑ ○ Sufficient carbohydrate and fat to meet energy requirements Anaemia ○ Epoetin alfa and darbepoetin alfa Dialysis Used for ATN and CKD in stage 5 Removes metabolic wastes and correct fluid and electrolyte abnormalities Primary reason: uremia or hyperkalemia unresponsive to other treatments Types: ○ Haemodialysis ○ Continuous renal replacement therapy ○ Peritoneal dialysis Haemodialysis Continuous Renal Replacement - Dialysing semi-permeable Therapy membrane - Limited to in-hospital AKI - Access: arteriovenous patients (AV) fistula - Filter and dialyse the blood - 3x/week; each session 4 without interruption hours long Peritoneal Dialysis Peritoneum Dialysis Access: dialysis catheter surgically placed in abdomen Types: ○ Continuous Ambulatory Peritoneal Dialysis (CAPD): exchanges performed by patients in their homes and without machines; instils in abdomen ○ Continuous Cycling Peritoneal Dialysis (CCPD): can also  be done at home; uses a special machine (cycler); exchanges occur while sleeping Transplantation Potential option for patients with ESRD Associated with a high degree of success Allows for ↑ independence Return to normal activities of daily living Normal renal function Antirejection drug therapy required: immunosuppressants Topic 3: GI System Disorders Peptic Ulcer Disease Peptic Ulcer Disease Pathophysiology 1. Helicobacter pylori (H. pylori) infection: - H. pylori is a gram-negative bacterium that colonises the stomach lining, causing chronic inflammation (gastritis) and disrupting the mucosal barrier. It weakens the protective mucous layer, allowing stomach acid to damage the underlying tissue, leading to ulcer formation. - The bacterium also releases urease, which converts urea to ammonia, neutralising stomach acid in its vicinity but causing localised damage. 2. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): - Long-term use of NSAIDs (e.g., aspirin, ibuprofen) inhibits an enzyme known as cyclooxygenase (COX). This enzyme is involved in the production of prostaglandins. Prostaglandins help maintain the mucosal barrier by promoting mucus and bicarbonate production and regulating blood flow to the stomach lining. - NSAID use reduces these protective factors, making the stomach lining more susceptible to injury by gastric acid. 3. Gastric Acid and Pepsin: - Gastric acid (HCl) and pepsin are essential for digestion, but they can also damage the mucosal lining if the protective barriers are weakened. - Excessive acid production, as seen in conditions like Zollinger-Ellison syndrome, can lead to ulcer formation, particularly in the duodenum. 4. Impaired Mucosal Defense: - The mucosal defence system includes mucus production, bicarbonate secretion, and tight epithelial cell junctions, which protect the stomach and duodenum from acid and pepsin. When these defences are weakened, the mucosa becomes vulnerable to injury. 5. Lifestyle Factors: - Smoking, excessive alcohol consumption, and stress are associated with an increased risk of PUD. Smoking can impair mucosal healing and increase acid production, while alcohol can directly irritate the stomach lining. Clinical Epigastric burning pain that is usually relieved by the intake of food Manifestations (especially dairy products) or antacids. The pain of gastric ulcers typically occurs on an empty stomach but may present soon after a meal.  Duodenal ulcer pain classically occurs 2 to 3 hours after a meal and is relieved by further food ingestion. Other manifestations that may occur in individuals with PUD include nausea, abdominal upset, and chest discomfort. A significant proportion of ulcers are asymptomatic, and life-threatening complications, such as GI bleeding, may occur in patients with no warning. The symptoms of PUD are not specific enough to allow for a diagnosis, and malignant conditions can mimic benign PUD. Diagnosis PUD Diagnosis H. Pylori Diagnosis - Upper GI barium contrast - Noninvasive radiography - Urease breath test - Endoscopy - Serological analysis - Faecal antigen testing - Invasive - Tissue urease test - Histologic analysis - Bacterial culture Treatment The treatment for PUD depends on: 1. Aetiology of the ulcer 2. Whether the ulcer is new or recurrent 3. Presence of any ulcer-related complications Overall treatment is aimed at: 1. Relieving the pain 2. Healing the ulcer 3. Preventing ulcer recurrence 4. Reducing ulcer related complications The major treatment objectives for PUD are to encourage healing of the injured mucosa by reducing gastric acidity and to prevent recurrence. Triple therapy for Peptic Ulcer Disease (PUD) refers to a standard treatment regimen designed to eradicate Helicobacter pylori (H. pylori) infection, which is a major cause of ulcers in both the stomach and duodenum. By eliminating H. pylori, this therapy reduces inflammation, allows ulcers to heal, and prevents recurrence. Components of Triple Therapy: 1. Proton Pump Inhibitor (PPI): - Drugs such as omeprazole, lansoprazole, esomeprazole, or pantoprazole. - Mechanism: PPIs reduce stomach acid production by inhibiting the proton pump (H+/K+ ATPase) in the stomach's parietal cells. This creates a less acidic environment, which promotes ulcer healing and enhances the effectiveness of antibiotics against H. pylori. 2. Antibiotic 1: Clarithromycin: - Mechanism: Clarithromycin is a macrolide antibiotic that inhibits protein synthesis in H. pylori, ultimately killing the bacteria. 3. Antibiotic 2: Amoxicillin or Metronidazole: - Amoxicillin: A broad-spectrum penicillin-type antibiotic that disrupts the bacterial cell wall. - Metronidazole: Used in patients who are allergic to penicillin. It works by interfering with the bacterial DNA synthesis of H. pylori. Standard Triple Therapy Regimen: PPI: Twice daily (e.g., omeprazole 20 mg or equivalent).  Clarithromycin: 500 mg twice daily. Amoxicillin: 1 g twice daily or Metronidazole: 500 mg twice daily for penicillin-allergic patients. Duration: Typically prescribed for 10 to 14 days. Treatment efficacy increases with longer regimens, generally up to 14 days for optimal results. Gastric Carcinoma Gastric Carcinoma Pathophysiology The Correa Cascade Stages 1. Normal Gastric Mucosa: Healthy gastric lining consists of normal epithelial cells with intact mucosal protection and regular function. 2. Chronic Non-atrophic Gastritis: This stage involves persistent inflammation of the stomach lining, often due to H. pylori infection. The gastric glands remain largely preserved at this point. 3. Chronic Atrophic Gastritis: Over time, chronic inflammation leads to atrophy (loss of normal gastric glands), replaced by fibrous tissue. Mucosal thinning occurs, resulting in reduced gastric acid production (hypochlorhydria). 4. Intestinal Metaplasia: The atrophic gastric mucosa undergoes intestinal metaplasia, where normal gastric epithelium is replaced by intestinal-type cells (goblet cells and absorptive cells). This change is an adaptation to chronic inflammation but is considered precancerous. 5. Dysplasia (Low and High Grade): Dysplasia involves abnormal growth and alterations in the structure and appearance of the cells. Low-grade dysplasia exhibits minimal cellular abnormalities, while high-grade dysplasia shows more pronounced abnormalities and a greater likelihood of progressing to cancer. 6. Intestinal-type Gastric Adenocarcinoma: The final stage in the cascade is the development of gastric adenocarcinoma, a malignant tumor that arises from dysplastic cells. Cancer cells invade deeper layers of the stomach wall and can metastasize to other organs. Factors Involved in the Correa Cascade: H. pylori Infection: This is the most significant risk factor, as H. pylori causes chronic inflammation and is closely linked to the early stages of the cascade, particularly chronic gastritis and atrophic gastritis.- Environmental Factors: Diet (high in salt, smoked, and processed foods), smoking, and alcohol consumption contribute to the progression of gastric lesions. Genetic Predisposition: Some individuals may have a genetic predisposition that increases their susceptibility to the development of gastric cancer. Importance of Early Detection: The stages of the Correa cascade represent a progressive transformation from inflammation to cancer. Early detection and intervention (for example, the eradication of H. pylori) can potentially halt or slow down progression to gastric cancer, especially at precancerous stages like intestinal metaplasia or dysplasia. Clinical In the early stages, gastric cancer often causes no symptoms, which is why it is Manifestations frequently diagnosed at an advanced stage. When symptoms do appear, they may include: Abdominal pain or discomfort.  Unintended weight loss. Nausea and vomiting, sometimes with blood (hematemesis). Dysphagia (difficulty swallowing). Early satiety (feeling full after eating only a small amount). Melena (black, tarry stools from bleeding). Fatigue due to anaemia (from chronic blood loss). Diagnosis Endoscopy with biopsy: This is the gold standard for diagnosing gastric carcinoma. ○ During an endoscopy, a biopsy of suspicious lesions can confirm cancer and determine the histological type. CT or MRI scans: Used to stage the cancer by assessing local invasion, lymph node involvement, and distant metastasis. Endoscopic ultrasound (EUS): Provides detailed imaging of the stomach wall layers and helps assess the depth of tumour invasion. Blood tests: May include testing for H. pylori, anaemia, and tumour markers (e.g., CEA, CA 19-9). Treatment 1. Surgical Management: Surgery is the primary curative treatment for early-stage and localised gastric cancer. Subtotal gastrectomy: Removes part of the stomach, typically used for tumours in the lower part of the stomach. Total gastrectomy: Removal of the entire stomach, usually for tumours involving the upper stomach. Lymph node dissection is often performed alongside to ensure complete removal of cancerous tissue. 2. Chemotherapy: Chemotherapy is used in advanced cases or as an adjuvant therapy to shrink tumours before surgery or to target residual cancer cells post-surgery. 3. Radiation Therapy: May be used alongside chemotherapy to help control local tumour growth, especially in cases where surgery is not an option or for palliative care. 4. Palliative Care: For advanced-stage gastric cancer, palliative care focuses on relieving symptoms and improving quality of life. This may include palliative chemotherapy, radiation, or surgery to address obstruction or bleeding. Colon Cancer Colon Cancer also known as Colorectal Cancer Pathophysiology Colon cancer typically arises through a multistep process involving genetic mutations and environmental factors. The progression usually occurs in the following stages: 1. Polyp Formation: - Most colon cancers begin as benign polyps. These small, abnormal growths on the inner lining of the colon can either remain benign or undergo further mutations that turn them into cancerous tumours. 2. Genetic Mutations: - Changes in key genes (e.g., APC, KRAS, TP53) contribute to the transformation of normal colon epithelial cells into  adenomatous polyps and eventually invasive cancer. 3. Invasion and Metastasis: - Once cancer has formed, it can invade deeper into the colon wall, reaching blood vessels and lymphatics, allowing cancer cells to spread (metastasise) to other parts of the body (e.g., liver, lungs). Clinical Symptoms may not appear in early stages but, as the cancer grows, patients may Manifestations experience: Changes in bowel habits: Diarrhoea, constipation, or a feeling that the bowel doesn’t empty completely. Blood in stool (hematochezia): Bright red or dark tarry stools. Abdominal pain or cramping. Unexplained weight loss. Fatigue due to anaemia from chronic blood loss. Narrow stools (in some cases, due to a tumour obstructing part of the colon). Screening and 1. Colonoscopy: Diagnosis - The gold standard for detection and prevention, as it allows for the direct visualisation of the entire colon and the removal of polyps during the procedure. 2. Faecal Occult Blood Test (FOBT) or Fecal Immunochemical Test (FIT): - These tests detect hidden blood in stool, which can be an early sign of colon cancer. 3. Stool DNA test (e.g., Cologuard): - Detects DNA changes in stool that may indicate the presence of colon cancer or large polyps. 4. Flexible Sigmoidoscopy: - Similar to colonoscopy but only examines the lower part of the colon (the sigmoid colon and rectum). 5. CT Colonography (Virtual Colonoscopy): - A non-invasive imaging test that uses CT scans to visualise the colon. Treatment 1. Surgical Resection: + Primary treatment for localized colon cancer. + Involves removing the affected part of the colon (colectomy) along with nearby lymph nodes. + Polypectomy: Removal of polyps during colonoscopy if the cancer is caught early. 2. Chemotherapy: + Used for more advanced cancers, particularly stage III (lymph node involvement) and stage IV. + Adjuvant chemotherapy (post-surgery) helps reduce the risk of recurrence. + Common chemotherapy drugs include 5-fluorouracil (5-FU), oxaliplatin, and capecitabine. 3. Radiation Therapy: + Not typically used for colon cancer but may be used in rectal cancer or for palliative purposes in advanced disease. 4. Palliative Care: + For advanced cases, palliative care focuses on symptom relief and improving quality of life, such as controlling pain, bleeding, or bowel obstruction. Alcoholic Liver Disease Alcoholic Liver Disease Pathophysiology There are three histologic stages of alcoholic liver disease: 1. Alcoholic Fatty Liver or Steatosis - At this stage, fat accumulates in the liver parenchyma. - Pathophysiology: Alcohol metabolism primarily occurs in the liver, where it is converted to acetaldehyde by alcohol dehydrogenase (ADH) and then to acetate. Excess alcohol intake overwhelms the liver’s ability to metabolise fat, leading to fat accumulation in liver cells (steatosis). - Reversibility: Fatty liver is generally asymptomatic and reversible with abstinence from alcohol. 2. Alcoholic Hepatitis - Pathophysiology: Prolonged alcohol use causes inflammation and damage to hepatocytes, leading to cell death and scarring. In this stage, there is marked inflammation, ballooning of hepatocytes, and infiltration of immune cells (such as neutrophils). Acetaldehyde, the toxic byproduct of alcohol metabolism, contributes to oxidative stress and mitochondrial dysfunction in the liver. - Patients may present with jaundice, fever, abdominal pain, fatigue, and anorexia. Severe cases can lead to liver failure. - Alcohol abstinence, nutritional support, treatment of infection, and prednisolone therapy in severe cases can help in the treatment of alcoholic hepatitis, but more severe cases lead to liver failure. 3. Alcoholic Cirrhosis - Cirrhosis is the end-stage of ALD, characterised by widespread fibrosis and regenerative nodules in the liver. Chronic inflammation leads to scarring, causing permanent damage and loss of normal liver architecture. As cirrhosis progresses, the liver loses its ability to function, resulting in hepatic decompensation. Liver damage at this stage is irreversible. Pathogenesis of ALD That leads to cellular damage in multiple ways: 1. Oxidative Stress: Alcohol metabolism produces reactive oxygen species (ROS), which damage cellular membranes, proteins, and DNA. 2. Acetaldehyde Toxicity: Acetaldehyde forms adducts with proteins, impairing normal cellular function and promoting inflammation. 3. Mitochondrial Dysfunction: Alcohol impairs mitochondrial energy production, contributing to liver cell death. 4. Immune Activation: Chronic alcohol use activates Kupffer cells (resident macrophages in the liver), releasing pro-inflammatory cytokines, which perpetuate liver injury.  5. Fibrosis: Repeated cycles of liver cell injury and repair lead to collagen deposition and fibrosis, eventually progressing to cirrhosis. Clinical Early-stage: Often asymptomatic. Mild symptoms may include fatigue, Manifestations weakness, and nausea. Alcoholic hepatitis: Jaundice, abdominal pain, fever, nausea, vomiting, and an enlarged liver. Cirrhosis: More severe symptoms such as jaundice, ascites, confusion (hepatic encephalopathy), easy bruising or bleeding, and swelling in the legs (edema). Screening and 1. Clinical History: A detailed history of alcohol intake is essential. Patterns Diagnosis of heavy, chronic alcohol use are key to diagnosis. 2. Laboratory Tests: - Liver function tests (LFTs): Elevated liver enzymes (AST > ALT with a ratio >2:1 is suggestive of alcoholic hepatitis), elevated bilirubin, and low albumin. - Complete blood count (CBC): May show macrocytic anaemia and thrombocytopenia (low platelets). - Prothrombin time (PTT) and International Normalised Ratio (INR): Elevated in more severe liver disease, indicating impaired liver function. 3. Imaging: - Ultrasound: Can detect fatty liver, hepatomegaly (enlarged liver), and signs of cirrhosis. - CT scan or MRI: May help identify liver lesions or ascites. 4. Liver Biopsy: In some cases, a biopsy is performed to confirm the diagnosis and assess the degree of inflammation, fibrosis, or cirrhosis. Treatment 1. Abstinence from Alcohol: Complete cessation of alcohol is the most important step in managing ALD. Continued alcohol use worsens liver damage and increases the risk of liver failure. Relapse prevention: Counselling, support groups (e.g., Alcoholics Anonymous), and medications such as naltrexone or acamprosate may be used to support sobriety. 2. Nutritional Support: Malnutrition is common in ALD. Nutritional support, including high- calorie and protein-rich diets, vitamins (especially B-complex vitamins and folate), and supplements, is crucial for recovery. 3. Medical Management: Corticosteroids (e.g., prednisolone) may be used in severe alcoholic hepatitis to reduce inflammation. 4. Treatment of Complications: Ascites: Managed with diuretics (e.g., spironolactone and furosemide), salt restriction, and occasionally paracentesis (removal of fluid). Hepatic Encephalopathy: Treated with lactulose to reduce ammonia levels and improve mental function. Oesophageal varices: Managed with beta-blockers to reduce bleeding risk, and endoscopic variceal ligation (EVL) if bleeding occurs. Infections: Patients with cirrhosis are at increased risk for infections such as spontaneous bacterial peritonitis (SBP), which requires prompt antibiotic treatment. 5. Liver Transplantation: For patients with end-stage liver disease (cirrhosis) who do not  improve with medical management, liver transplantation may be considered. Typically, candidates must demonstrate a period of sustained abstinence (e.g., six months) to be eligible for transplantation. Cirrhosis Cirrhosis Possible Causes 1. Viral infection like from hepatitis C or B. The virus gets in those liver cells, attacks them and they no longer function and do their jobs so the patient can develop scarring of the liver. 2. Heavy alcohol consumption 3. Increased fat collection in the liver and this causes hyperlipidemia. We see a rise in this due to increased number of people with obesity 4. Patients who do not manage their cholesterol they have long-term hyperlipidemia - can lead to this condition as well 5. Problems with the bile duct - liver and gallbladder work together. Liver produces bile which goes down through the common bile duct and is stored in the gallbladder until you need that bile to help digest the fats in your food. If there are gall stones, it can cause that bile not to drain down properly which can backflow into the liver and damage those cells hence over time leading to cirrhosis. 6. Autoimmune condition that attacks hepatocytes. Cirrhosis is the late-stage, irreversible scarring (fibrosis) of the liver caused by long-term liver damage from these various causes which can cause chronic liver diseases. It disrupts the liver's normal architecture, impairs its ability to function, and can lead to life-threatening complications. As a result of repeated injury to liver cells, it leads to inflammation, cell death, and fibrotic tissue formation. Pathophysiology Cirrhosis is the result of chronic liver injury leading to: 1. Hepatocyte Death: Chronic injury (from alcohol, viruses, fat, etc.) causes liver cells (hepatocytes) to die. 2. Inflammation and Fibrosis: As liver cells die, the liver tries to repair itself, but this repair involves the activation of stellate cells which produce collagen and fibrous tissue, leading to scarring. 3. Nodular Regeneration: The liver attempts to regenerate hepatocytes, but instead of regenerating in a normal architecture, nodules form within the fibrotic tissue. 4. Impaired Blood Flow: The scarring distorts the liver's structure, leading to portal hypertension (increased pressure in the portal vein system) and reduced blood flow through the liver. 5. Liver Dysfunction: As the disease progresses, the liver’s ability to perform essential functions (e.g., protein synthesis, detoxification, bile production) diminishes. Confusion + Treatment: Administer lactulose Asterixis Portal Hypertension Portal Hypertension Hepatic portal vein– the large vein that carries blood from the digestive tract, spleen and pancreas, to the liver. Within the liver, blood runs through tiny channels where it exchanges contents with the liver cells. This is where nutrients are processed, toxins and pathogens are removed from the blood before it  exits the liver, via the hepatic veins, to enter the general circulation. Possible Causes Cirrhosis (most common cause): Scar tissue obstructs blood flow through the liver. Cirrhosis and fibrosis narrow the liver sinusoids, increasing vascular resistance within the liver. Serum transaminases (AST/ALT) will be normal or slightly elevated Splanchnic Vasodilation: The body compensates by dilating blood vessels in the abdominal organs (splanchnic vasodilation), which increases blood flow to the portal system, further elevating portal pressure. Formation of Collateral Vessels: New blood pathways form to bypass the liver, causing varices (enlarged veins) in areas such as the oesophagus, stomach, and rectum. These vessels are fragile and prone to rupture. Complications Arising from Increased Pressure: Elevated pressure in the portal system leads to complications, including splenomegaly (enlarged spleen), ascites (fluid accumulation in the abdomen), and the risk of spontaneous bacterial peritonitis. Any obstruction to the flow of blood may result in a rise in portal venous pressure proximal to the level of blockage. This condition is called portal hypertension and is a central pathophysiologic event in many liver diseases Clinical 1. Abdominal distension, known as ascites - a result of fluid leaking into the Manifestations abdominal cavity under high blood pressures. 2. Enlarged spleen due to congestion of the splenic veins. 3. Formation of so-called collateral vessels as alternative routes for blood to bypass the liver. These new blood vessels connect some digestive organs directly to the general circulation. By doing so, they reduce blood flow through the portal vein and relieve portal pressures, but they may also cause serious complications. 4. As blood pressures increase, these small vessels can become engorged and form varices, which may rupture and bleed. Variceal bleeding can be massive and life-threatening. 5. Because collateral vessels direct blood away from the liver, toxins that are normally removed by the liver can now reach the general circulation and pass into the brain, causing symptoms such as confusion, drowsiness, tremor, or even coma, in a condition known as hepatic encephalopathy Treatment TIPS (Transjugular Intrahepatic Portosystemic Shunt) is primarily used to decrease portal pressure and manage variceal bleeding or refractory ascites. Hepatorenal Syndrome Hepatorenal Syndrome Hepatorenal Syndrome (HRS) is a type of kidney failure that occurs in people with advanced liver disease, most commonly cirrhosis. This syndrome results from changes in blood flow within the kidneys due to severe liver dysfunction. Despite normal kidney structure, the kidneys begin to fail as blood flow is diverted away from them due to the effects of liver disease. Pathophysiology The exact mechanism of hepatorenal syndrome is complex, involving changes in blood flow dynamics and hormonal regulation: 1. Portal Hypertension and Splanchnic Vasodilation: + In advanced liver disease, increased pressure in the portal vein causes blood vessels in the splanchnic (abdominal) circulation to dilate. + This leads to a redistribution of blood volume, with more blood  pooling in the abdomen and less being available for vital organs, including the kidneys. 2. Reduced Blood Flow to Kidneys: + The kidneys receive less blood flow as the body attempts to compensate for low blood pressure by constricting the renal blood vessels. + This reduced flow triggers kidney dysfunction, despite normal kidney anatomy and function otherwise. 3. Hormonal Dysregulation: + Hormones such as renin, angiotensin, norepinephrine, and vasopressin increase in an attempt to maintain blood pressure. + These hormones cause constriction of blood vessels in the kidneys, further reducing kidney blood flow and worsening renal function. Findings Elevated serum creatinine and oliguria without other identifiable causes Hepatic Encephelopathy Hepatic Encephelopathy It is a brain dysfunction caused by liver dysfunction because liver isn’t filtering out toxins as it should. There are many theories about the pathogenesis of Hepatic encephalopathy, but ammonia plays a central role in all of them. Pathophysiology 1. Ammonia Toxicity: Ammonia crosses the blood-brain barrier, leading to astrocyte swelling and brain edema. 2. Neurotransmitter Dysfunction: Abnormal levels of neurotransmitters such as GABA, glutamate, and serotonin affect brain function. 3. Oxidative Stress and Inflammation: Elevated levels of toxins cause oxidative stress and inflammation, further impairing brain cells. Treatment Treated with lactulose to reduce ammonia levels and improve mental function. Hepatocellular Carcinoma Hepatocellular Carcinoma Hepatocellular carcinoma (HCC) is the most common primary liver cancer and typically arises in the setting of chronic liver disease, especially in patients with cirrhosis or chronic viral hepatitis (such as hepatitis B or hepatitis C). It’s a major cause of cancer-related deaths worldwide due to its aggressive nature and often late diagnosis. Pathophysiology Pathophysiology of Hepatocellular Carcinoma is multifactorial. 1. Chronic Liver Disease and Cirrhosis: + Chronic liver diseases, especially those causing cirrhosis, such as hepatitis B, hepatitis C, alcoholic liver disease, and non-alcoholic fatty liver disease (NAFLD), are significant risk factors. Cirrhosis leads to fibrosis and liver cell damage, which triggers cycles of cell death and regeneration, increasing the risk of mutations in hepatocytes and the development of cancerous cells. 2. Genetic and Molecular Mechanisms: + Chronic inflammation and oxidative stress lead to genetic mutations in hepatocytes, promoting carcinogenesis. 3. Viral Integration (Hepatitis B): + Hepatitis B virus can integrate into the host DNA, promoting  genetic instability and oncogene activation, which contributes to HCC development even in non-cirrhotic livers. 4. Angiogenesis: + HCC tumours are highly vascular and promote the formation of new blood vessels to support tumour growth. Diagnosis Imaging: ○ Ultrasound, CT, and MRI scans help visualise liver tumours, with contrast-enhanced studies showing characteristic patterns. Blood Tests: ○ Alpha-fetoprotein (AFP) is a tumour marker for HCC, though it may not be elevated in all cases. Biopsy: ○ Generally avoided if imaging and AFP are diagnostic, as biopsy can carry the risk of tumour spread. Management 1. Surgical Resection: Potentially curative in early-stage disease without widespread liver dysfunction or cirrhosis. 2. Liver Transplantation: Best option for small HCC in patients with severe cirrhosis, as it removes the tumour and the diseased liver. 3. Locoregional Therapies: + Radiation: Destroys cancer cells using high-frequency radio waves. + Transarterial chemoembolisation (TACE): Delivers chemotherapy directly to the tumour’s blood supply, slowing its growth. 4. Palliative Care: Symptomatic relief and supportive care for advanced, non-resectable cases. Prognosis The prognosis depends on the stage at diagnosis and the underlying liver function. Early detection improves outcomes, but HCC is aggressive, with a high rate of recurrence even after treatment. Regular screening in high-risk individuals, such as those with chronic liver disease, is essential to detect HCC early. Topic 4: Neuro System Disorders Stroke Stroke Pathophysiology Transient Ischemic Ischaemic Stroke Haemorrhagic Stroke Attacks (TIA) Thrombotic Intracerebral Atherosclerosis Bleeding within plaque the brain Large Vessel Occurs without (MCA Infarct) warning Small Vessel Caused by: ○ Hypertension (Lacunar Infarct) ○ Thrombolytic Embolic drugs Dislodge of Subarachnoid blood clots Bleeding in  Carotid plaque Subarachnoid Atrial Fibrillation space Atherosclerotic Severe plaques headache Associate with activities Caused by: Aneurysm rupture Assessment and Assess Airway, breathing, Circulation (ABC) and vital signs Stabilisation in Provide oxygen if hypoxemic A&E Obtain IV access Obtain blood samples - Check blood sugar, treat if needed Perform neurologic screening assessment - include GCS/NIHSS Activate stroke team - Order Immediate brain CT scan Obtain 12-lead ECG Diagnostic Test - Imaging test - CT brain - MRI - Angiogram - Blood flowing test - Carotid Ultrasound - 2D Echo - Electrical activity test - EEG Supportive Airway support and ventilatory assistance if decreased consciousness or Measures bulbar dysfunction compromises the airway Supplemental oxygen only if needed to maintain oxygen saturation > 94% Correction of hyperthermia (temperature > 38° C) by using an antipyretic drug and identifying and treating the cause of hypothermia Treatment of hypoglycemia (blood glucose < 60 mg/dL) Treatment of hyperglycemia (a reasonable option) to lower blood glucose to 140 to 180 mg/dL while closely monitoring for hypoglycemia Targeted temperature management (TTM) is often used in neurocritical care to minimise secondary neurologic injury and improve outcomes.TTM encompasses therapeutic hypothermia, controlled normothermia, and treatment of fever. GCS Score Eye opening 4 - spontaneously 3 – to voice 2 – to pain 1 - none Best verbal 5 – oriented response 4 – confused 3 – inappropriate words 2 – incomprehensible sounds 1 - none Best motor 6 – obeys commands  response 5 – localises pain 4 – withdrawal 3 – abnormal flexion 2 – abnormal extension 1 - none Scoring GCS 3 - 8 = coma GCS 9 - 12 = moderate HI CGS 13 - 15 = fully conscious Traumatic Brain Injury (TBI) Traumatic Brain Injury (TBI) Types: Primary or direct injury ○ Caused by impact or initial insult ○ Include diffuse axonal injury and the focal lesions of laceration, contusion, and haemorrhage Secondary injury ○ Progressive damage resulting from a physiologic response to an initial insult ○ Damage results from the subsequent brain swelling, infection, and cerebral hypoxia. ○ Often diffuse or multifocal, including concussion, infection, and hypoxic brain injury Types Primary Secondary ○ Focal - coup ○ Polar ○ Diffuse ○ Intracranial hematomas Epidural Subdural Subarachnoid Conditions Trauma Causing Brain Tumours Injury Stroke Metabolic derangements Degenerative disorders Clinical Changes in level of consciousness Manifestations Alterations in sensory and motor functions Cranial nerve reflexes Level of consciousness – may fluctuate; RAS-dependent ○ Confusion ○ Delirium ○ Obtundation ○ Stupor ○ Coma Pupil reflex ○ Function of the brainstem and CN II and III ○ Indicator of brain herniation ○ Increasing ICP may impair eye movements controlled by CN III, IV and VI Oculovestibular reflex ○ Brainstem dysfunction ○ Doll’s eye test Corneal reflex ○ Absence of blink response, indicator of severely impaired brain function  Causes Motor vehicle collisions (civilian and sports) Industrial accidents Minor head injuries Criminal assault In the USA, head injury causes more deaths and disability than any other neurological condition before age 50 Occurs in > 70% of accidents Mortality from severe HI is around 50% and only modestly reduced by treatment Skull Fracture Skull Fracture Fractures of cranial Vault: ○ Obvious in x-ray skull Linear ○ Lucent lines indicate bone separation and dense lines, overlap ○ Causes rupture of meningeal vessels Depressed ○ Stellate: impact by blunt objects. Underlying brain injury ○ Eggshell: child abuse ○ Open fractures associated with infections Basal skull fractures ○ Difficult to detect in X-rays (irregular, dense bones) Other soft tissue injuries may give clue ○ Hemotympanum (blood in middle ear) ○ CSF rhinorrhea (nose) & otorrhea (ear) ○ Postauricular ecchymoses (Battle’s sign) ○ Periorbital ecchymoses (Raccoon’s eyes) Basilar Skull Fracture Head Injury Head Injury Intracranial lesions ○ Concussion ○ Contusion ○ Extradural haematoma ○ Subdural haematoma Acute  Chronic ○ Subarachnoid hemorrhage ○ Intracerebral hemorrhage Concussion Immediate transient LOC: Dazed, ‘star-struck’ Cause Rotation of the cerebral hemispheres on the relatively fixed brainstem Electro-physiological dysfunction of the reticular activating system No structural lesion & residual sequelae Clinical Features Amnesia may occur after injury Retrograde amnesia ○ Memory loss for events before the injury ○ May indicate severity of the lesion Antegrade amnesia ○ For events after, very brief Contusion Head injury resulting in hemorrhage into brain tissue Cause Due to deceleration of the brain against the skull rupturing the blood vessels on the surface of the brain Frontal and occipital poles affected Coup injury ○ Directly under point of impact Contrecoup injury ○ At a point opposite to the point of impact Clinical features Hemiparesis or gaze paralysis may occur with frontal injuries Visual defect in occipital injuries Cranial nerve dysfunction - commonly olfactory More severe injury causes cerebral edema, decorticate or decerebrate rigidity If cerebral lesions are bilateral ⇒ coma Extra/ epidural Bleeding is between skull & dura mater: Haematomas Due to direct trauma causing # temporal bone and damage to middle meningeal artery As the bleeding is arterial, there is rapid worsening of the patient’s condition Clinical Features Brief LOC (due to concussion) followed by a short "lucid interval" then, coma again (progressive neurological deterioration due to herniation) Carries a bad prognosis Usually requires surgical evacuation Untreated: decerebrate rigidity, coma, death Acute Subdural Bleeding is between dura mater and arachnoid membrane Haematomas May not be associated with any surface injuries on the scalp Follows severe head injury – change in velocity Due to rupture of surface cerebral veins that join the dural venous sinuses Twice as common as extradural hematoma Clinical Features Brief LOC (due to concussion) followed by a relatively longer "lucid interval" then, coma again (progressive neurological deterioration due to herniation) Carries a bad prognosis if associated with cerebral injury due high velocity Usually requires surgical evacuation  Untreated: decerebrate rigidity, coma, death Chronic Common in elderly people >60 years Subdural Cause Haematomas Follows minor injuries which may not be remembered Due to shrinking of the brain coupled with fragility of blood vessels Clinical Features Signs & symptoms appear months to years after trivial injury Due to slow accumulation of venous blood around atrophied brain Subarachnoid Thunderclap headache - Inflammation of vessels in meninges and of perivascular dura Haemorrhage Assessment of Vital signs – ABC HI Secure airway and IV line Protect cervical spine in collar No morphine or depressants! Hourly vital signs, GCS Arrange for urgent CT scan head Neurological assessment for severity of head injury Management Minor injuries ○ Fully conscious, no deficits ○ Admission and observation if necessary Intermediate ○ Confusion, brief LOC, neurological deficit ○ CT scans, MRI Severe ○ In coma ○ Investigations ○ Resuscitation and ICP management ICP Management Blood pressure ○ Keep the blood pressure at the usual level (MAP 90 mmHg) ○ Raising it too much will result in increase in bleeding or edema ○ Too low pressure - inadequate CPP ○ Maintain CPP between 50 – 70 mmHg Prognostic Factors Neuropsychologic disturbances (impaired concentration, attention, memory) are more common cause of disability than specific neurologic deficits Posttraumatic anosmia rarely resolves GCS < 8 – needs formal rehabilitation Guillain-Barre Syndrome (GBS) - Patients often experience paresthesia or dysesthesia. Decerebrate Rigidity - Abnormal extension of all four limbs Decorticate Rigidity - Abnormal flexion of all four limbs Multiple Sclerosis (MS) - Early clinical characteristic: Vision loss Meningitis  - Sudden fever (39°C), severe headache, nausea or vomiting, double vision, drowsiness, sensitivity to bright light, and a stiff neck - CSF would show an increased protein, decreased glucose and increased neutrophil levels. Topic 5: Reproductive System Disorders Male Benign Prostatic Hyperplasia (BPH) Benign Prostatic Hyperplasia (BPH) Seen in 80% of men > 60 years of age Aetiology unknown; ageing male hormone system Occurs in elderly men causing frequency of urination Pathophysiology As prostate tissue increases, it compresses urethra and bladder outlet Enlarged prostatic gland may lead to urinary obstruction Static – increase in prostatic size Dynamic – prostatic smooth muscle tone Manifestations - Obstruction to flow - Decreased stream - Hesitancy; difficulty initiating a stream Management 1. Dihydrotestosterone (DHT) (Finasteride, Dutasteride etc.) 2. 5 α-reductase inhibitors - help to relax the prostatic smooth muscle tone. 3. Surgically treated by transurethral prostatectomy (TURP) Diagnosis 1. IPSS score of 20 2. DRE (prostate feels smooth) 3. PSA (0-4ng/ml) Prostate Cancer Prostate Cancer Pathophysiology Multi-step process that involve genes that control cell differentiation and growth Family history, dietary fats Protective factors: dietary fat reduction, vit. D, E and selenium intake, soy, green tea and tomato-rich products Diagnosis Rectal exam Biopsy Serum prostate-specific antigen Trans rectal ultrasonography Treatment Watchful waiting Radical prostatectomy, radiation therapy or cryotherapy, depending on the staging and age Stage I: Watchful waiting Stage I and II: Cryotherapy Stage I-IV: Radiation therapy Stage I-IV: Radical prostatectomy Stages III & IV: Hormone Therapy Stages III & IV: Chemotherapy  Cryotherapy Freezes cancerous tissues using gases. Biopsies are used to monitor cancer after treatment Radiation Uses high energy beams to kill cancerous cells. Therapy Radical Involves the surgical removal of the prostate and the Prostatectomy cancerous tissues nearby. Hormone therapy Treatment for advanced cancer using LHRH agonist. Anti-androgens are prescribed during initial treatment. Gleason Score Grade group 1: Gleason score 6 or lower (low-grade cancer) from Biopsy Grade group 2: Gleason score 3 + 4 = 7 (medium-grade cancer) Grade group 3: Gleason score 4 + 3 = 7 (medium-grade cancer) Grade group 4: Gleason score 8 (high-grade cancer) Grade group 5: Gleason score 9 to 10 (high-grade cancer) Erectile Dysfunction Erectile Dysfunction Inability to achieve and maintain an erection sufficient for sexual intercourse Pathophysiological Arterial insufficiency Decreased blood flow to the penis potentially caused by Outcome radiation or contributed by diabetes. Cavernous fibrosis Loss of smooth penile muscle. Excess Collagen Formation of scar tissue which may lead to Peyronie’s Deposition disease. Endothelial Lack of nitric oxide reduces blood supply to the penis. Dysfunction Causes - Anti-androgens (hormone therapy) - Chemotherapy drugs. - Radical prostatectomy - Lifestyle (diet, smoking, alcohol) Categories Psychogenic Neurogenic Hormonal Vasculogenic Medication-induced Treatment - Lifestyle Changes - Psychotherapy - Pharmaceutical Therapy major PDE5 inhibitors are sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra), and avanafil (Stendra). - Surgical Therapy 1. Psychotherapy and Lifestyle Changes 2. Pharmaceutical Therapy  3. Surgical Therapy Female Pelvic Inflammatory Disease Pelvic Inflammatory Disease Risk Factors 1. Unprotected Sexual Activity 2. History of STIs 3. Multiple Sexual Partner 4. Douching 5. Recent Insertion of an Intrauterine Device (IUD) 6. Young Age (Under 25) 7. Previous Episode of PID 8. Engagement in High-Risk Sexual Behaviours 9. Partner with an STI 10. Low Socioeconomic Status and Limited Access to Healthcare Clinical Symptoms of Lower Abdominal or Pelvic Issues: Manifestation 1. Lower Abdominal or Pelvic Pain: This is the most common symptom. 2. Abnormal Vaginal Discharge: This may have an unpleasant odour. 3. Irregular Menstrual Bleeding: This can include heavy or painful periods. 4. Fever and Chills: These symptoms may occur, especially in severe cases. 5. Painful Urination or Intercourse: You may experience discomfort during urination or sexual activity. 6. Nausea and Vomiting: These symptoms may arise if the infection is advanced. Diagnosis Pelvic Examination: Checks for pain and tenderness in the reproductive organs. STI Testing: Detects Chlamydia or Gonorrhea, the common pathogens. Ultrasound: Helps visualise any abscesses or structural abnormalities. Laparoscopy: A minimally invasive surgery to view the pelvic organs directly, especially in cases with complications or uncertain diagnosis. Management To manage an infection effectively, here is an outline of systemic and surgical approaches, particularly for infections affecting the pelvic region: 1. Systemic Control of Infection Antibiotic Therapy: Administer antibiotics targeted to the specific infectious organism, based on culture and sensitivity results, to effectively eliminate the infection. Treat with: ○ Cefixime 400mg orally stat + Doxycycline 100mg bd for 14 days + Metronidazole 400mg bd for 6 days ○ Or if penicillin allergic Cefixime 400mg orally stat Erythromycin 500mg orally ods for 14 days + Metrodinazole 400 400mg bd for 5 days ○ Analgesics: Use analgesics to relieve pain associated with the infection. ○ Antipyretics: Administer antipyretics to reduce fever and manage systemic symptoms. ○ IV Therapy: Ensure adequate hydration and medication delivery through intravenous therapy, especially in severe or systemic infections. 2. Surgical Intervention Goal: Perform surgery to address the infection while aiming to  preserve pelvic organs. Fertility Preservation: Surgical techniques should focus on preserving fertility, especially in younger patients or those who wish to have children in the future. Patient - Refrain from Sexual Intercourse: Education - Advise the patient to avoid sexual intercourse until the full course of treatment is completed, as reinfection or transmission could occur if either partner is untreated. - Alcohol Avoidance with Metronidazole: - Inform the patient to avoid alcohol consumption while taking Metronidazole and for at least 48 hours after completing the course. - Combining alcohol with Metronidazole can cause adverse reactions, including nausea, vomiting, and abdominal cramps. - Oral Contraceptive (COCP) Considerations: - Explain that antibiotics may reduce the effectiveness of combined oral contraceptives (COCP). Advise using a backup contraceptive method (e.g., condoms) during and for seven days after completing the antibiotic course. - Importance of Compliance: - Emphasise the importance of taking all prescribed medication as directed, even if symptoms improve, to ensure full eradication of the infection and prevent antibiotic resistance. - Follow-Up: - Advise on the need for follow-up appointments to confirm treatment efficacy and check for any lingering symptoms or complications. Reinforce the importance of attending these appointments for optimal recovery. - Information Leaflet and Contact Tracing: - Provide an information leaflet detailing the condition, treatment plan, and lifestyle precautions. - Offer a contact tracing card if the infection is communicable, to discreetly notify any other individuals who may be affected. Endometriosis Endometriosis Pathophysiology Endometriosis is a chronic gynaecological condition in which tissue similar to the lining of the uterus (the endometrium) grows outside the uterus. This tissue can implant on various organs within the pelvis, including the ovaries, fallopian tubes, bladder, and even the intestines. Endometriosis can cause significant pain, menstrual irregularities, and fertility issues. It most commonly affects women in their mid-30s who have not given birth (nulliparous) and is more prevalent in Asian women (51%) compared to Caucasian women (22%). Commonly in ovaries Pathophysiology of Endometriosis 1. Retrograde Menstruation: Menstrual blood flows backwards through the fallopian tubes into the pelvic cavity, where endometrial cells can implant and grow. 2. Immune System Disorders: Some believe that an immune system dysfunction allows endometrial-like cells to grow outside the uterus. 3. Coelomic Metaplasia: The cells lining the pelvic organs may transform into endometrial cells due to hormonal or environmental factors. 4. Genetic Factors: A family history of endometriosis can increase a  woman’s risk. Once these cells are outside the uterus, they continue to respond to the hormones of the menstrual cycle, leading to inflammation, scar tissue formation, and adhesions. Clinical Symptoms of endometriosis can vary significantly among women, with some Manifestation experiencing severe pain while others have minimal or no symptoms at all. Common symptoms include: 1. Pelvic Pain: Often severe, particularly around the time of menstruation. 2. Dysmenorrhea (Painful Periods): Intense cramps that may increase in severity over time. 3. Dyspareunia (Pain During Intercourse): Discomfort during intercourse caused by adhesions or lesions. 4. Heavy or Irregular Menstrual Bleeding: This includes menorrhagia (excessive bleeding) and bleeding between periods. 5. Pain with Bowel Movements or Urination: These symptoms often occur during menstrual periods. 6. Infertility: Endometriosis is one of the leading causes of infertility, as scar tissue can hinder egg release, fertilisation, or implantation. Diagnosis 1. Pelvic Examination: To check for abnormalities, although it may not reveal small implants. 2. Ultrasound: Useful for identifying ovarian cysts (endometriomas) but may not detect all endometrial growths. 3. Magnetic Resonance Imaging (MRI): Offers a more detailed view but is generally used in complex cases. 4. Laparoscopy: A minimally invasive surgery to visualise and sometimes biopsy lesions; considered the gold standard for diagnosis. 5. Hysteroscopy: A hysteroscopy can help diagnose and treat endometriosis by providing a direct view of the uterine cavity and allowing for tissue biopsy samples Management - Laparoscopy is the gold standard for both the diagnosis and treatment of Laparoscopy endometriosis. This minimally invasive surgical procedure allows doctors to directly visualise the pelvic organs and identify endometrial implants, adhesions, and cysts (endometriomas) outside the uterus, which are hallmarks of Endometriosis. 1. Accurate Diagnosis: Endometriosis is often difficult to diagnose based on symptoms alone, as they can mimic other conditions (e.g., pelvic inflammatory disease or irritable bowel syndrome). Laparoscopy is the only method that allows direct visualisation and diagnosis, with biopsy if needed. 2. Staging of Endometriosis: Laparoscopy enables surgeons to assess the extent and location of endometriosis, categorising it into stages I to IV (minimal, mild, moderate, or severe) based on the American Society for Reproductive Medicine (ASRM) guidelines. This helps guide treatment planning and provide information on prognosis, especially for fertility. 3. Treatment During Procedure: Laparoscopy allows the surgeon to treat endometriosis during the procedure by: a. Excision or Ablation: Endometrial implants can be removed (excised) or destroyed (ablated) with techniques like laser or cautery. b. Adhesiolysis: Adhesions (scar tissue) between pelvic organs can be removed to restore normal anatomy, helping to relieve pain and improve fertility. c. Cystectomy: Endometriomas (ovarian cysts associated with  endometriosis) can be removed to preserve ovarian function and improve fertility outcomes. Benefits of Laparoscopy for Endometriosis Minimally Invasive: Compared to open surgery, laparoscopy uses small incisions, reducing recovery time, postoperative pain, and scarring. Shorter Recovery Time: Patients can typically return to daily activities within a few days to weeks. Lower Complication Rates: Laparoscopy has a lower risk of infection and postoperative complications compared to open surgeries. Management - - Imaging technique Hysteroscopy - View the endometrium - Assessment of uterus, cornua - Biopsy - Hysteroscopy is an imaging technique performed in the operating room in order to view the lining of the uterus (endometrium). This is done using a thin tool with a light and camera (the hysteroscope) attached to its tip. - The doctor gently inserts this into the vagina, through the cervix, and into the uterus. With this technique, a surgeon will be able to see if there is any uterine cause for heavy menstrual bleeding, pelvic pain, or infertility. - For women who have suspected endometriosis and infertility, it is very common that if there is to be a laparoscopy, then hysteroscopy be performed for assessment of the uterus, the cornua (the technical name for the entrance of the tubes into the uterus) and for a biopsy of the lining to look for any contribution to infertility in this area. Treatment 1. Conservative Management