isurg

Station 39: AMYLOIDOSIS What is meant by amyloid? SpoilerAmyloid is an abnormal fibrillar protein that is deposited in the extracellular tissue. The proteins are deposited in a rigid, mesh-like, sheet structure. What is amyloidosis or amyloid degeneration? SpoilerAmyloidosis is a life-threatening condition in which there is deposition of abnormal fibrillar proteins known as amyloid in the extracellular tissue. Why do amyloid deposits in chronic infection not resolve? SpoilerHumans are susceptible to the complications of the amyloid protein because they have no enzyme that can break this structure down. What are the common sites of amyloid deposition? SpoilerBased on the clinical features of AL and AA amyloidosis common sites of amyloid deposition include: Kidneys (leading to proteinuria and nephrotic syndrome) Heart (leading to restrictive cardiac disease and arrhythmias) Liver (Hepatomegaly) Spleen (Splenomegaly) Nervous System (Peripheral neuropathy, carpal tunnel syndrome, autonomic neuropathy) Gastro-intestinal tract (Macroglossia, bleeding, poor absorption) What are the different types of amyloid protein? SpoilerAL protein (associated with Multiple Myeloma/Immunocyte dyscrasias, i.e., Primary amyloidosis) AA protein (associated with Chronic inflammatory conditions e.g., T.B., Rheumatoid arthritis, Secondary amyloidosis) β₂ or microglobulin (Aβ₂m) protein (associated with Chronic renal failure or dialysis, i.e., Hemodialysis-associated amyloidosis). Note: Familial amyloidosis is also mentioned, caused by a mutation in transthyretin. Which type of amyloidosis occurs in chronic inflammation? SpoilerAA amyloidosis (or Secondary amyloidosis) occurs in chronic inflammation. Examples of chronic inflammatory conditions include: -Rheumatoid arthritis (commonest cause of AA amyloid in the UK) -Inflammatory bowel disease -Tuberculosis (T.B.) -Bronchiectasis -Osteomyelitis -Renal cell carcinoma What are the main clinical findings in amyloidosis? SpoilerThe clinical features depend on the type (AL vs. AA) and organs involved. The patient description in your prompt suggests AL amyloidosis due to the presence of: -Progressive ankle swelling / Pitting pedal oedema (suggests kidney/cardiac involvement) -Frothy urine / 3+ Proteinuria (Kidney involvement: Proteinuria and nephrotic syndrome) -Fatigue -Numbness in his feet (Nervous system involvement: Peripheral neuropathy) -Large, firm tongue / Macroglossia (Gastro-intestinal tract involvement) -Hepatomegaly (Liver involvement) How is amyloidosis classified? SpoilerAmyloidosis is classified by the protein and the system involved. Classification by Protein Involved (Systemic/Generalized Amyloidosis) • AL amyloid (Immunocyte dyscrasias with monoclonal B-cell proliferations like Multiple myeloma) • AA amyloid (Chronic inflammatory conditions) • Familial amyloidosis (Autosomal dominant disorder, commonly caused by a mutation in transthyretin) Classification by Clinical Type • Primary Amyloidosis: Associated with Immunocyte dyscrasias (e.g., Multiple myeloma), involving the AL protein. • Secondary Amyloidosis: Associated with Chronic inflammatory conditions (e.g., T.B., bronchiectasis), involving the AA protein. • Haemodialysis-associated amyloidosis: Associated with Chronic renal failure or dialysis, involving the β₂-microglobulin (Aβ₂m) protein. How to test for amyloidosis? SpoilerBlood and urine tests may provide hints about the diagnosis, but the gold standard for detecting amyloid deposits is to perform Congo red staining on a tissue sample, which appears apple-green when viewed with a polarizing microscope. Laser microdissection followed by mass spectrometry can determine the type of amyloid in virtually 100% of cases.

Stem: A 45-year-old, diagnosed & managed for acute pancreatitis 2 weeks ago. Now presents with vomiting, SOB & epigastric pain which is not improved with PPIs. Examination revealed tachycardia & tachypnoea. Which enzymes to be checked apart from amylase & lipase? SpoilerLactate dehydrogenase Is amylase and lipase valuable? and why? SpoilerLipase levels are more specific to the pancreas. While amylase is not specific and can be normal if measured too early or too late because of its short half-life. What are Causes of post-cholecystectomy pancreatitis ? SpoilerIatrogenic injury infectious retained stones stricture. Patient comes with jaundice and ascending cholangitis 6 months after surgery, reason? SpoilerRetained stone causing obstruction Stricture 5 weeks after the initial attack patient presented with epigastric fullness, vomiting and dyspepsia, diagnosis? SpoilerPancreatic pseudocyst Define pseudocyst and what are its contents? Collection of amylase-rich fluid enclosed in a wall of fibrous or granulation tissue. Difference between cancer & pseudocyst? Tumour- Pseudocyst Fluid viscosity: Elevated -Low Tumour marker CA19-9: High -Low Amylase: Low- High What is the difference between true cyst and pseudocyst? SpoilerPseudocyst is not closed and doesn't have a lining of epithelial cells separating it from the nearby tissue, instead its wall made up of fibrous and granulation tissue. In case of pancreatic necrosis, what investigation of choice? SpoilerCT abdomen with IV contrast pancreatic protocol (thin CT slices). What are the findings to look for in CT? SpoilerFat stranding Oedema Collection Pseudocyst Abscess Necrosis What are the biochemical findings? SpoilerHyperglycaemia Hypocalcaemia Hypomagnesemia Hypoalbuminemia. Why is the calcium level low? SpoilerIn early stages Auto-digestion of mesenteric fat by pancreatic enzymes and release of free fatty acids (chelate calcium), which form calcium salts (saponification of fat). Later stages, due to complication like: -Sepsis -Hypoalbuminemia -Transient hypoparathyroidism Why is there hyperglycaemia? SpoilerDestruction of B cells of islets of Langerhans that normally secret insulin. Could be due to stress response (cortisol and catecholamines). How could you classify obstructive jaundice according to cause? SpoilerIntra-luminal: stone Trans-luminal: cholangiocarcinoma Extra-luminal: cancer of head of pancreas What could the cause for silent obstructive jaundice? SpoilerCarcinoma of head of pancreas How would you manage a patient with acute pancreatitis? SpoilerCCrISP protocol using the ABCDE approach Admission to HDU/ICU. Analgesia Aggressive fluid rehydration Supplemental oxygen Monitoring -Central venous pressure -Urine output -Blood gases -Liver function, U&E -Clotting profile -Serum calcium -Blood glucose -Nasogastric drainage (only initially) Antibiotics if -If suspected cholangitis -Sepsis -Necrosis -Pre-invasive intervention (ERCP). Octreotide → decrease pancreatic secretions PPI → prevent stress ulcers CT scan if -Organ failure -Clinical deterioration -Signs of sepsis ERCP within 72 hours for -Severe gallstone pancreatitis -Or signs of cholangitis Supportive therapy for organ failure if it develops → (inotropes, ventilatory support, hemofiltration, etc.) If nutritional support is required → nasojejunal tube. What scoring for pancreatitis do you know? Talk about each of them Glasgow criteria: PANCREAS SpoilerPaO₂ < 8 kPa (normal: 10–13 kPa) Age > 55 Neutrophils > 15,000 Calcium < 2 mmol/L (after 48h) Renal (urea) > 16 mmol/L (normal: 2.5–6.7) Enzymes (LDH) > 600 (after 48h) Albumin < 32 g/L (after 48h) Sugar (glucose) > 10 mmol/L (at least 3 of the above = severe episode = ITU admission) Ranson's criteria SpoilerEstimates mortality of patients with pancreatitis, based on initial and 48-hour lab values. Criteria at time of patient admission to hospital Age > 55 WBC > 16,000 Glucose > 11 mmol/L (> 200 mg/dL) AST > 250 IU/L LDH > 350 IU/L Within 48 hours Hct drops 10% or greater Fluid sequestration > 6 L Calcium < 2.0 mmol/L (< 8 mg/dL) PO₂ < 60 mmHg (< 8 kPa) BUN rises more than 1.98 mmol/L (> 5 mg/dL) after IV fluid hydration Base deficit > 4 mmol/L Mortality prediction 0–2 points: Mortality is 1% 3–4 points: Mortality is 16% 5–6 points: Mortality is 40% 7–11 points: Mortality almost 100% What are the early and delayed complications of acute pancreatitis? Early SpoilerNecrosis ARDS Pleural effusion Electrolyte disturbance: Hyperglycaemia Hypocalcaemia Hypomagnesemia Hypoalbuminemia Late !Pseudocyst Splenic vein thrombosis How to treat splenic vein thrombosis in a patient with haemorrhagic pseudocyst? SpoilerMultidisciplinary approach including: -Gastroenterologist/hepatologist -Haematologist -Interventional radiologist → For radiological intervention (coiling) Complications of coiling? Injury to surrounding structures Haemorrhage Failure Infection Abx in pt with acute pancreatitis? SpoilerQuinolones or according to Trust guidelines Management of pain? SpoilerAccording to WHO analgesic ladder but I will try to avoid morphine and NSAID. Starting with non-opioid like paracetamol, then weak opioid like (codeine), then strong opioid (pethidine), then PCA (patient-controlled analgesia), and epidural analgesia. Why not morphine? SpoilerCauses constriction of sphincter of Oddi. Is it true or theoretical? SpoilerTheoretical What is CRP? SpoilerNonspecific acute phase reactant protein made by the liver released into the blood in response to inflammation. Causes of tachypnoea in this patient? SpoilerARDS as complication Sympathetic overactivation Compression of diaphragm by pseudocyst Exocrine enzymes of the pancreas? SpoilerAmylase: breaks down carbohydrates into simple sugars like glucose. Proteases: break down proteins into amino acids. The main proteases are trypsin, chymotrypsin, and carboxypeptidase. Lipase: breaks down fats into fatty acids and glycerol. Other than the enzymes what is present in pancreatic juice? SpoilerBicarbonate: neutralizes the acidic chyme from stomach, creating an alkaline environment that is optimal for the activity of pancreatic enzymes. Water: helps to dilute the chyme and facilitate transport of nutrients. Electrolytes: such as sodium, potassium. The secretion of pancreatic juice is stimulated by factors including: -Acetylcholine: released by the vagus nerve, stimulates the secretion of pancreatic enzymes. -Cholecystokinin (CCK): a hormone released by the duodenum in response to the presence of fatty acids and amino acids, stimulates the secretion of pancreatic enzymes and contraction of the gallbladder. -Secretin: a hormone released by the duodenum in response to the presence of acid, stimulates the secretion of bicarbonate-rich fluid by the pancreas. How is the pancreatic secretion stimulated? SpoilerAcid load in the duodenum plays a crucial role in stimulating pancreatic secretion. When acidic chyme enters the duodenum from the stomach, it triggers the release of secretin, which stimulates the pancreas to secrete bicarbonate-rich fluid. This fluid neutralizes the acid, creating an alkaline environment that is necessary for the activity of pancreatic enzymes.