CDM revision SEM 1 Flashcards

Question

How to separate pre-renal uraemia from acute tubular necrosis

Answer 1

Prerenal uraemia - kidneys hold on to sodium to preserve volume

Answer 2

Symptoms include weakness, leg cramps, palpitations secondary to cardiac arrhythmias and ascending paralysis. Causes can be secondary to: 1.) Increased potassium loss: Drugs: thiazides, loop diuretics, laxatives, glucocorticoids, antibiotics GI losses: diarrhoea, vomiting, ileostomy Renal causes: dialysis Endocrine disorders: hyperaldosteronism, Cushing's syndrome ``` 2.) Trans-cellular shift Insulin/glucose therapy Salbutamol Theophylline Metabolic alkalosis ``` 3. ) Decreased potassium intake 4. ) Magnesium depletion (associated with increased potassium loss) ECG changes seen in hypokalaemia include: U waves T wave flattening ST segment changes Treatment of hypokalaemia depends on severity. Any causative agents should be removed. Gradual replacement of potassium via the oral route is preferred if possible. Mild to moderate hypokalaemia 2.5 - 3.4 mmol/l can be treated with oral potassium provided the patient is not symptomatic and there are no ECG changes. Severe hypokalaemia (<2.5mmol/l) or symptomatic hypokalaemia should be managed with IV replacement. The patient should be managed in an area where cardiac monitoring can take place. If there are no contraindications to fluid therapy (e.g. volume overload, heart failure) potassium should be diluted to low concentrations as higher concentrations can be phlebitic. The infusion rate should not exceed 20mmol/hr. In this case, 3 bags of 0.9% Saline with 40mmol KCL is the correct answer.

Answer 3

Genetics located on chromosome 14 inherited in an autosomal recessive / co-dominant fashion* alleles classified by their electrophoretic mobility - M for normal, S for slow, and Z for very slow normal = PiMM homozygous PiSS (50% normal A1AT levels) homozygous PiZZ (10% normal A1AT levels) Features patients who manifest disease usually have PiZZ genotype lungs: panacinar emphysema, most marked in lower lobes liver: cirrhosis and hepatocellular carcinoma in adults, cholestasis in children Investigations A1AT concentrations spirometry: obstructive picture Management no smoking supportive: bronchodilators, physiotherapy intravenous alpha1-antitrypsin protein concentrates surgery: lung volume reduction surgery, lung transplantation

Answer 4

scites is the abnormal accumulation of fluid in the abdomen. The causes of ascites can be grouped into those with a serum-ascites albumin gradient (SAAG) <11 g/L or a gradient >11g/L as per the table below: SAAG > 11g/L (indicates portal hypertension) SAAG <11g/L Liver disorders are the most common cause cirrhosis/alcoholic liver disease acute liver failure liver metastases Cardiac right heart failure constrictive pericarditis ``` Other causes Budd-Chiari syndrome portal vein thrombosis veno-occlusive disease myxoedema ``` SAAG <11g/L Hypoalbuminaemia nephrotic syndrome severe malnutrition (e.g. Kwashiorkor) Malignancy peritoneal carcinomatosis Infections tuberculous peritonitis ``` Other causes pancreatitisis bowel obstruction biliary ascites postoperative lymphatic leak serositis in connective tissue diseases ```

Answer 5

Drug-induced liver disease is generally divided into hepatocellular, cholestatic or mixed. There is however considerable overlap, with some drugs causing a range of changes to the liver ``` The following drugs tend to cause a hepatocellular picture: paracetamol sodium valproate, phenytoin MAOIs halothane anti-tuberculosis: isoniazid, rifampicin, pyrazinamide statins alcohol amiodarone methyldopa nitrofurantoin ``` The following drugs tend to cause cholestasis (+/- hepatitis): combined oral contraceptive pill antibiotics: flucloxacillin, co-amoxiclav, erythromycin* anabolic steroids, testosterones phenothiazines: chlorpromazine, prochlorperazine sulphonylureas fibrates rare reported causes: nifedipine Liver cirrhosis methotrexate methyldopa amiodarone

Answer 6

Budd-Chiari syndrome, or hepatic vein thrombosis, is usually seen in the context of underlying haematological disease or another procoagulant condition. Causes polycythaemia rubra vera thrombophilia: activated protein C resistance, antithrombin III deficiency, protein C & S deficiencies pregnancy combined oral contraceptive pill: accounts for around 20% of cases The features are classically a triad of: abdominal pain: sudden onset, severe ascites → abdominal distension tender hepatomegaly Investigations ultrasound with Doppler flow studies is very sensitive and should be the initial radiological investigation

Answer 7

Management reducing dietary sodium fluid restriction is sometimes recommended if the sodium is < 125 mmol/L aldosterone antagonists: e.g. spironolactone loop diuretics are often added. Some authorities only add loop diuretics in patients who don't respond to aldosterone agonists whereas other authorities suggest starting both types of diuretic on the first presentation of ascites drainage if tense ascites (therapeutic abdominal paracentesis)-give albumin give prophylactic antibiotics(cipro) large-volume paracentesis for the treatment of ascites requires albumin 'cover'. Evidence suggests this reduces paracentesis-induced circulatory dysfunction and mortality paracentesis induced circulatory dysfunction can occur due to large volume paracentesis (> 5 litres). It is associated with a high rate of ascites recurrence, development of hepatorenal syndrome, dilutional hyponatraemia, and high mortality rate prophylactic antibiotics to reduce the risk of spontaneous bacterial peritonitis. NICE recommend: 'Offer prophylactic oral ciprofloxacin or norfloxacin for people with cirrhosis and ascites with an ascitic protein of 15 g/litre or less, until the ascites has resolved' a transjugular intrahepatic portosystemic shunt (TIPS) may be considered in some patients

Answer 8

Patients may present similarly with **acute alcoholic hepatitis** **Other causes of confusion** (which may be present in a patient with liver disease) and should always be considered when a patient with chronic liver disease presents confused - Delirium – which can be secondary to many causes but often infection - Head injury – subdural haematoma - Alcohol withdrawal - Drugs

Answer 9

The commonest causes of raised unconjugated bilirubin in adults are: - Gilbert’s syndrome: - A genetic disorder where less of the enzyme that breaks down Bilirubin (UDP-glucuronyltransferase) is produced. It affects 5% of the population. There is an increase in the bilirubin often with fasting or concurrent illness. - Confirmation of just a predominant unconjugated hyperbilirubinaemia makes the diagnosis of Gilbert’s syndrome virtually certain. This does not require any treatment and the patient can be completely reassured. - Rarely does it cause a bilirubin above 68umol/L - Haemolysis: - The breakdown of red blood cells. There can by many causes for this and standard investigations for this would include: reticulocyte count, LDH, blood film, Haptoglobin, Direct coombs test - Drug related, for example, the antibiotic Rifampicin impairs the uptake of Bilirubin In healthy adults conjugated bilirubin is virtually absent. Levels usually start to become increased when the liver has lost approximately ½ of its excretory capacity. It is therefore usually a sign of liver disease, which may be acute or chronic in nature. Common causes for elevated conjugated bilirubin include**:** - Biliary obstruction at any level of the bile ducts - Often secondary to gallstones in the common bile duct, but also from malignancy – commonly Cholangiocarcinoma or Pancreatic cancer - Cholestatic drug reactions - Potentially any drug, but commonly antibiotics such as Nitrofuratoin and Penicillin - Autoimmune Cholestatic disease e.g. Primary Sclerosing Cholangitis (may occur at any level) and Primary Biliary Cirrhosis (intrahepatic ducts) - Hepatitis of any origin where there is significant impairment in liver function - Cirrhosis

Answer 10

**Causes of this acute**: The most likely cause of this presentation is that this man has decompensated liver disease with encephalopathy. Things which may may cause a patient to decompensate include - Upper GI bleed - Spontaneous bacterial peritonitis - Infection (any source) - Constipation - Drugs – prescription or recreational - Dehydration - Alcohol – either a binge or withdrawal - Portal vein thrombosis

Answer 11

common in female-damage to intrahepatic ducts Presentation-no symptoms,itch,Sjorens,jaundice ,fatigue,poor memory Labs-raised ALP ,raised IgM,AMA,biopsy-granulomatous lymphatic cholangitis(not needed-florid ducts, duct loss) Exclude other causes treatment-UDCA Itch-Cholestyramine, rifampicin, gabapentin Treat symptoms-fatigue Monitering-itch,osteoporosis,cirrhosis liver transplant

Answer 12

Any age Can be precipitated by drugs such as statins, statins,nitrofurantoin types type 1-80%(ANA/ASMA) type 2-<10%(liver kidney microsomal LKM,liver cystosol antibody-high risk outcome presentation-fatigue,aneroxia,nausea,joint pain, acute hepatitis jaundice ``` labs raised ALT ANA/ASMA RAISED IgG usually need biopsy confirm fibrosis ``` Treatment-aim for normal ALT and IgG lifelong immunosupression -predinsolone,Azathioprine,MMF,tacrolimus,liver transplant

Answer 13

Inflammation and fibrosis of both intra and extra hepatic bile ducts 70-80% have IBD(UC) symptoms-asymptomatic,fatique,itch,RUQ pain,cholangitis,jaundice and complication labs-raised ALP,MRCP shows beads on string appearance CT not helpful US normal biopsy-onion skin treatment IBD-colonoscopy Itch-same as PBC manage cholangitis if causing symptoms Complications bone disease cholangiocarcinoma (in 10%) increased risk of colorectal cancer liver transplantation

Answer 14

Wilson’s disease is a rare progressive genetic disorder, which results in accumulation of copper in the body’s tissues. In particular it affects the brain, liver and cornea of the eyes. Untreated it may lead to liver fibrosis and cirrhosis, along with central nervous system dysfunction. There are 500 gene mutations known about. These result in dysfunction in Wilson’s ATPase(ATP7B-helps Cu bind to ceruloplasmin and form vesicles to be excreted in the bile), which usually moves copper from along intracellular membranes in the liver. The defective ATPase results in accumulation of copper in the liver, resulting in damage. Over time as the liver becomes damaged the copper is released into the blood and causes other end organ damage. Patients may present with: **Liver dysfunction (most common presentation):** · Decompensated liver cirrhosis · Acute liver failure (often associated with renal failure and haemolytic anaemia) **Central nervous system (usually have established liver disease):** · Asymmetrical tremor in ½ patients with CNS dysfunction · Poor co-ordination and clumsiness · Speech and language problems · Neuropsychiatric illness – commonly severe depression or neurotic behaviours Enlarged liver and spleen Renal disease due to damage to distal renal tubules hemolytic anemia **Ophthalmological** · Kayser-Fleischer ring present in 95% of those with neurological disease (seen on slit-lamp), 50% of those without. May occur in other diseases. · Sun-flower cataracts – seen on slit lamp. Do not impair vision **Diagnosis**. Consider in any patient of any age with unusual liver or neurological abnormalities. There is no one best test for diagnosis. Presence of Kayser-Felischer ring and low serum caeruloplasmin (<0.1g/L) is enough to establish diagnosis. Caeruloplasmin is a protein made in the liver that stores and carries copper around the blood. This may be low in Wilson’s as copper is not able to bind to the protein causing instability. Serum Caeruloplasmin is can be affected by many factors and is not diagnostic on it’s own. Other markers of disease include 24hour urinary copper, serum free copper and hepatic copper (liver biopsy). A scoring system also exists to help with diagnosis. Genetic screening is complex, many patients are compound heterozygotes (carry two different defective genes) and it can take many months to complete. **Treatment** Treatment is life-long. It involves using medication to either promote urinary excretion or to decrease intestinal absorption. The commonest medication used is D-Penicillamine. Zinc salts,trientine,tetrathiomolybdate Genetics are complex due to the number of gene variations, but essentially siblings (25% risk) and any offspring (0.5% risk) should be offered genetic screening.

Answer 15

I-irritabilty ii-confusion iii-incoherent inappropriate behaviour, restless iv-coma ``` Precipitating factors infection e.g. spontaneous bacterial peritonitis GI bleed post transjugular intrahepatic portosystemic shunt constipation drugs: sedatives, diuretics hypokalaemia renal failure increased dietary protein (uncommon) ``` Management treat any underlying precipitating cause NICE recommend lactulose first-line, with the addition of rifaximin for the secondary prophylaxis of hepatic encephalopathy lactulose is thought to work by promoting the excretion of ammonia and increasing the metabolism of ammonia by gut bacteria antibiotics such as rifaximin are thought to modulate the gut flora resulting in decreased ammonia production other options include embolisation of portosystemic shunts and liver transplantation in selected patients

Answer 16

ALF-HE defining feature – drugs (inc paracetamol, abx and anti-epileptics), viruses (typically hepatitis A, B and E), toxins (classically mushroom poisoning, many herbal remedies are implicated), vascular causes (e.g. budd chiari or ischaemic/hrpoxic hepatitis), pregnancy-related and some miscellaneous causes e.g. acute and fulminant presentation of Wilson disease/AIH) and malignant infiltration of the liver, typically by breast cancer or lymphoma

Answer 17

ALF due to paracetamol ``` Arterial pH <7.3 after resuscitation and>24 hours since ingestion Lactate >3 mmol/L or The 3 following criteria: HE >Grade 3 Serum creatinine >300 µmol/L INR >6.5 ``` ALF not due to paracetamol ``` INR >6.5 or 3 out of 5 following criteria: Aetiology: indeterminate aetiology, hepatitis, drug-induced hepatitis Age <10 years or >40 years Interval jaundice encephalopathy >7 days Bilirubin >300 µmol/L INR >3.5 ```

Answer 18

Medical Untreated or progressive infection Clinically apparent extrahepatic or metastatic malignancy Progressive hypotension, resistant to vasopressor support Clinically significant ARDS, FiO2 > 0.8 Fixed dilated pupils > 1 hour in the absence of thiopentone Severe coexistent cardiopulmonary disease HIV? psychiatric Multiple episodes of self harm (>5) within an established pattern of behaviour (esp. if non-drug methods used) Consistently stated wish to die, in the absence of established mental illness Chronic refractory schizophrenia or other mental illness, resistant to therapy Incapacitating dementia or mental retardation Active intravenous drug abuse or oral polydrug use Alcohol dependence or abuse

Answer 19

Ethanol is metabolized in the liver by two pathways, resulting in an increase in the NADH/NAD ratio. The altered redox potential causes increased hepatic fatty acid synthesis with decreased fatty acid oxidation; both events lead to hepatic accumulation of fatty acid,which is then esterified to glycerides. The changes in oxidation–reduction also impair carbohydrate and protein metabolism and are the cause of the centrilobular necrosis of the hepatic acinus that is typical of alcohol damage. TNFα release from Kupffer cells causes the release of reactive oxygen species,leading, in turn, to tissue injury and fibrosis.Acetaldehyde is formed by the oxidation of ethanol, and its effect on hepatic proteins may well be a factor in producing liver cell damage. n addition to fatty change, there is infiltration by polymorphonuclear leucocytes and hepatocyte necrosis, mainly in zone 3. Dense cytoplasmic inclusions called Mallory bodies are sometimes seen in hepatocytes and giant mitochondria are also a feature. Mallory bodies are suggestive of, but not specific for, alcoholic damage, as they can be found in other liver disease, such as Wilson's disease and primary biliary cholangitis. If alcohol consumption continues, alcoholic hepatitis may progress to cirrhosis.

Answer 20

Alcoholic liver disease covers a spectrum of conditions: alcoholic fatty liver disease alcoholic hepatitis cirrhosis tender hepatomegaly Selected investigation findings: gamma-GT is characteristically elevated the ratio of AST:ALT is normally > 2, a ratio of > 3 is strongly suggestive of acute alcoholic hepatitis Hypoglycemias,Increased MCV,thrombocytopenia Selected management notes for alcoholic hepatitis: glucocorticoids (e.g. prednisolone) are often used during acute episodes of alcoholic hepatitis Maddrey's discriminant function (DF) is often used during acute episodes to determine who would benefit from glucocorticoid therapy it is calculated by a formula using prothrombin time and bilirubin concentration pentoxyphylline is also sometimes used the STOPAH study (see reference) compared the two common treatments for alcoholic hepatitis, pentoxyphylline and prednisolone. It showed that prednisolone improved survival at 28 days and that pentoxyphylline did not improve outcomes

Answer 21

The two known mutations of HFE are C282Y and H63D. Testing for these is simple and cheap. But there are other rare genes that may cause disease Whilst this is an autosomal recessive condition, clinically things can be a bit more complex – this is because gene expression (penetrance) varies. E.g. just because you have two copies of the defective gene does not mean you will definitely develop the clinical condition. - C282Y/C282Y Homozygous gives a 95% risk of iron overload - C282Y/H63D compound heterozygotes gives around 4% risk (increased risk with increased alcohol intake, viral hepatitis) - H63D/H63D Homozygous is least likely to cause iron overload All these genes lead to increased intestinal absorption of iron.

Answer 22

resenting features early symptoms include fatigue, erectile dysfunction and arthralgia (often of the hands) 'bronze' skin pigmentation diabetes mellitus liver: stigmata of chronic liver disease, hepatomegaly, cirrhosis, hepatocellular deposition) cardiac failure (2nd to dilated cardiomyopathy) hypogonadism (2nd to cirrhosis and pituitary dysfunction - hypogonadotrophic hypogonadism) arthritis (especially of the hands) Increase risk if pseudo put Questions have previously been asked regarding which features are reversible with treatment: ``` Reversible complications Irreversible complications Cardiomyopathy Skin pigmentation Liver cirrhosis** Diabetes mellitus Hypogonadotrophic hypogonadism Arthropathy ``` Typical iron study profile in patient with haemochromatosis transferrin saturation > 55% in men or > 50% in women raised ferritin (e.g. > 500 ug/l) and iron low TIBC

Answer 23

Who is an risk? All overweight/obese individuals (50% of population) Older sedentary individuals Type 2 diabetics/metabolic syndrome Often goes undiagnosed as is it frequently asymptomatic and raised liver enzymes frequently ignored How are patients with NAFLD typically identified? Raised liver enzymes Imaging evidence of steatosis Present with imaging evidence of cirrhosis/liver cancer (too late!) dIAGNOSIS Raised ALT and/or GGT and evidence of steatosis on imaging Imaging evidence of steatosis Raised ALT and/or GGT and evidence of insulin resistance / central obesity / metabolic risk factors No history of excess alcohol (<14/21 units/week) No known pre-existing liver disease No hepatotoxic drugs Negative blood screen for other liver diseases (viral, autoimmune etc) Liver biopsy may be required if there is diagnostic uncertainty xRaised IgA in 46% Raised ferritin with normal transferrin saturation in 33% ``` Staging for fibrosis FIB-4 score NAFLD fibrosis score ELF test Fibrotest ProC3 ``` Transient elastography Acoustic force radiation imaging (ARFI) MR elastography Generally tests are reasonably good at differentiating patients in to no/mild fibrosis or advanced fibrosis/cirrhosis, but inaccurate in providing an exact fibrosis stage

Answer 24

``` General Lifestyle intervention (aim to lose >10% bodyweight) Specialist diet/exercise advice Weight loss adjuncts (orlistat) Modify cardiovascular risk Bariatric surgery (if meet criteria) ``` F0-F1 As above Fibrosis reassessment every 3 years ``` F2-F3 Non-diabetic Vitamin E Clinical trial Diabetic Regimen including GLP-1 or Pioglitazone or empagliflozin Clinical trial ``` ``` Cirrhosis Surveillance for HCC Variceal screening Bone density assessment Clinical trial ```

Answer 25

Suggested medical follow up: - Hepatocellular carcinoma: screening ultrasound and AFP every 6 months - Variceal Haemorrhage: OGD at diagnosis of cirrhosis and every 2 years - Beta-blocker (non-cardio-selective; carvedilol or propranol) as primary prevention of bleeding rebleed - Viral Superinfection: Immunise for HAV and HBV (although this patient has already been exposed to HBV therefore would not require additional vaccination) - Osteoporosis: Screen & treat - Ascites & SBP: Monitor regularly for evidence of ascites & treat - Vitamin deficiencies: Treat (Vit B Co-strong & Thiamine) - Ongoing review with addiction services to help maintain abstinence from alcohol and illicit drugs.

Answer 26

For many years the Child-Pugh classification was used to classify the severity of liver cirrhosis. However, in recent years the Model for End-Stage Liver Disease (MELD) has been increasingly used, particularly patient's who are on a liver transplant waiting list Child-Pugh classification ``` Score 1 2 3 Bilirubin (µmol/l) <34 34-50 >50 Albumin (g/l) >35 28-35 <28 Prothrombin time, prolonged by (s) <4 4-6 >6 Encephalopathy none mild marked Ascites none mild marked ``` Summation of the scores allows the severity to be graded either A, B or C: < 7 = A 7-9 = B > 9 = C MELD Uses a combination of a patient's bilirubin, creatinine, and the international normalized ratio (INR) to predict survival. A formula is used to calculate the score: MELD = 3.78×ln[serum bilirubin (mg/dL)] + 11.2×ln[INR] + 9.57×ln[serum creatinine (mg/dL)] + 6.43 ``` The 3-month mortality based on MELD scores: 40 or more: 71.3% mortality 30 - 39: 52.6% mortality 20 - 29: 19.6% mortality 10 - 19: 6.0% mortality < 9: 1.9% mortality ```

Answer 27

``` Chronic liver failure UKELD ≥ 49 (Specific variant syndromes) Hepatocellular carcinoma multiple: up to 5 tumours ≤ 3cm single: up to 5cm (or 7cm if stable) (Acute liver failure) ```

Answer 28

Several models are available to determine the severity of alcoholic hepatitis. The Maddrey discriminant function (DF), Model for End-stage Liver Disease (MELD) and Glasgow alcoholic hepatitis score (GAH) can all be used to assess the severity of alcoholic hepatitis. These scores are predominantly based on laboratory parameters. Determining severity of alcoholic hepatitis is important to highlight patients with poor short-term survival and those who would benefit from pharmacological intervention. Maddrey discriminant function The DF score has been traditionally use to assess the severity of alcoholic hepatitis. It is based on serum bilirubin and prothrombin time. DF = (4.6 x [prothrombin time (sec) - control prothrombin time (sec)]) + (serum bilirubin/17.1) Serum bilirubin (umol/L) Severe alcoholic hepatitis is defined as a DF score ≥ 32. The 28 day (one month) mortality among patients with a DF ≥32 ranges from 25-45%. Patients with a score < 32 have mild-to-moderate alcoholic hepatitis, which has a <10% mortality at 1-3 months. Glasgow alcoholic hepatitis score The GAH is a newer scoring system, which also predicts mortality among patients with alcoholic hepatitis. It is a slightly more complex score based on age, white blood cell count, urea, bilirubin and prothrombin time. A score ≥ 9 is consistent with severe alcoholic hepatitis and associated with a poor 28-day and 84-day survival (46% and 40%, respectively).

Answer 29

Oesophagus ``` Oesophagitis Varices Malignancy Gastro-oesophageal reflux disease (GORD) Mallory-Weiss tear Stomach ``` ``` Peptic ulcer disease Mallory-Weiss tear Gastric varices Gastritis Malignancy Duodenum ``` ``` Peptic ulcer disease Diverticulum Aortoduodenal fistula Duodenitis Other ``` There are many other causes of upper GI bleeding though they are relatively less common. Swallowed blood Bleeding disorders Dieulafoy's lesion Aortoenteric fistula Hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) Gastric antral vascular ectasia (GAVE, watermelon stomach)

Answer 30

``` Risk factors Several risk factors increase the likelihood of a patient developing an UGIB. NSAIDs Anticoagulants Alcohol abuse Chronic liver disease Chronic kidney disease Advancing age Previous PUD or H. pylori infection NSAID-use ``` NSAIDs inhibit the synthesis of prostaglandins, which are gastroprotective. Prostaglandins work by inhibiting enterochromaffin-like cells, which are involved in the secretion of histamine. Histamine stimulates parietal cells to secrete hydrochloric acid. Therefore, inhibition of prostaglandins leads to excessive HCl secretion and damage to the underlying mucosa. Clinical features The two characteristic clinical findings of UGIB are haematemesis and melaena. Haematemesis refers to vomiting blood. Haematemesis may present with bright red bleeding or as ‘coffee-ground’ vomitus. Melaena is the passage of ‘black, tarry stool’, which has an offensive odour. The colour is due to partly digested blood. Symptoms ``` Haematemesis Dizziness Syncope Weakness Abdominal pain Dyspepsia Heartburn Melaena Haematochezia (passage of fresh blood per rectum) Weight loss Signs ``` ``` Dehydration Pallor Confusion Tachycardia and hypotension Abdominal tenderness Melaena Haematochezia (10-15% of patients with acute, severe haematochezia have an UGIB) Stigmata of liver disease (e.g. spider naevi, ascites, hepatomegaly) Telangiectasia ```

Answer 31

Upper GI endoscopy is the main diagnostic test. It should be completed immediately in any unstable patient following initial resuscitation, or within 24 hours in all other patients. arly risk stratification helps identify high-risk patients & need for prompt intervention. Two scoring systems are used in patients presenting with UGIB. UGIB scoring systems Blatchford score The Blatchford score takes into account a number of different clinical findings, biochemical parameters and past medical history. NICE recommends it is used during the primary assessment, followed by the Rockall score post-endoscopy. Similar to the Rockall score, a score of 0 on the Blatchford score is associated with a low risk of mortality and patients can be considered for early discharge and non-admission. Rockall scoring The Rockall score is comprised of both a pre- and post-endoscopy score that can be added together to give an overall value. The pre-endoscopy score is composed of three parts: Age (0-2) Shock (0-2) Co-morbidity (0-3) Patients with a score of 0 are at low risk of re-bleeding and death. This group of patients (approx. 15%) may be discharged early or not admitted. The post-endoscopy score is composed of two sections: Diagnosis (0-2) Bleeding (0, 2) This score can be remembered using the mnemonic ABCDE: ``` Age Blood pressure (and heart rate) Comorbidity Diagnosis Endoscopic findings ```

Answer 32

All patients presenting with an UGIB should initially be resuscitated with respects to airway (A), breathing (B) and circulation (C). Resuscitation ``` Airway Patent and protected Breathing Saturations Respiratory rate Breath sounds Circulation Blood pressure & heart rate ECG Establish IV access (two wide-bore cannula) Take blood (e.g. FBC, U&Es, clotting, LFTs, cross match) IV fluid if appropriate (0.9% normal saline) Consider blood products Endoscopy ``` Following resuscitation, unstable patients should be transferred for an immediate endoscopy. It is recommended that all other patients have endoscopy within 24 hours of admission. Management can then be divided according to ‘non-variceal’ or ‘variceal' bleeding. Non-variceal bleeding The most common cause of non-variceal upper GI bleeding is peptic ulcer disease. The need for intervention depends on the characterisation of the ulcer, which can be classified using the Forrest classification (beyond the scope of these notes). Management below focuses mainly on that of peptic ulcer disease. Alternative pathologies may be treated slightly differently (e.g. argon photocoagulation for angiodysplasia). A number of techniques can be employed at the time of endoscopy to treat non-variceal causes of UGIB. In general, dual therapy should be given (i.e. adrenaline plus another modality) Mechanical (e.g. clips) with adrenaline Thermal coagulation with adrenaline Proton pump inhibitor therapy should be reserved for patients with a non-variceal UGIB with evidence of recent haemorrhage during endoscopy. A repeat endoscopy should be completed in patients who re-bleed, or are suspected to be high-risk of re-bleeding. Unstable patients who re-bleed post-endoscopy should be offered radiological (e.g. embolisation) or surgical intervention. Variceal bleeding Pharmacological intervention ``` Terlipressin (IV injection) Analogue of vasopressin (ADH) Causes splanchnic vasoconstriction This reduces portal pressures Prophylactic antibiotic therapy Reduces the risk of spontaneous bacterial peritonitis Endoscopic intervention ``` Variceal band ligation (VBL) Completed acutely. Patients then need to undergo variceal banding programme every 2-4 weeks until varices have gone. Endoscopic sclerotherapy Alternative option to VBL that involves injection of a sclerosing agent. Failed intervention Patients may re-bleed despite endoscopic therapy. An initial re-attempt of variceal band ligation may be appropriate. If these attempts fail, further options include: Sengstaken-blakemore tube: Bridging therapy, at risk of oesophageal necrosis if left > 24 hours. Oesophageal stent: Alterantive to Sengstaken-blakemore tube. Transjugular intrahepatic portosystemic shunt (TIPS) procedure: Interventional radiological procedure to create a shunt between portal and systemic venous circulation to reduce portal pressure. A definitive treatment in appropriately selected patients.

Answer 33

- **Renal disorders are the most common cause of secondary hypertension. They include:** - Chronic pyelonephritis - Diabetic nephropathy - Glomerulonephritis - Polycystic kidney disease - Obstructive uropathy - Renal cell carcinoma - **Other causes of secondary hypertension are:** - **Vascular disorders, including:** - Coarctation of the aorta — usually results in upper-limb hypertension. There can be a significant difference in blood pressure between the left and right arms. Other signs include absent or weak femoral pulses, radio-femoral delay, palpable collateral blood vessels in the back muscles, and a suprasternal murmur radiating through to the back. - Renal artery stenosis — suspect this if the person has peripheral vascular disease and an abdominal bruit, or if blood pressure is resistant to treatment. - **Endocrine disorders, including:** - Primary hyperaldosteronism — probably the most common curable cause of hypertension. People usually present with hypokalaemia, alkalosis (elevated bicarbonate level), and plasma sodium level greater than 140 mmol/L, or a larger than expected decrease in serum potassium when using a low-dose thiazide-type diuretic. The symptoms may be non-specific, but rarely it may present with tetany, muscle weakness, nocturia, or polyuria. Treatment with a calcium-channel blocker can mask the features of primary hyperaldosteronism. After identification of a possible adrenal adenoma on CT scan or MRI (magnetic resonance imaging), tertiary referral is required for confirmation of unilateral aldosterone excess and possible laparoscopic adrenalectomy. - Phaeochromocytoma — people can present with intermittently high or labile blood pressure, or postural hypotension, headaches, sweating attacks, palpitations, or unexplained fever and abdominal pains. Alternatively, it can be asymptomatic. It is the rarest but most important cause of hypertension to diagnose because malignant transformation or catastrophic haemorrhage from the tumour can be fatal. - Cushing's syndrome — suspect this when clinical features are present (for example truncal obesity and striae). It rarely presents as hypertension alone. - Acromegaly — suspect this if clinical features are present (for example enlargement of hands and feet, facial changes, sweating). - Hypothyroidism — hypertension may result from altered levels of renin, angiotensin, and aldosterone, and is associated with an increased diastolic blood pressure. Clinical features may include fatigue, weight gain, dry skin and hair loss, constipation, and muscle weakness. See the CKS topic on [Hypothyroidism](https://cks.nice.org.uk/topics/hypothyroidism/) for more information. - Hyperthyroidism — increased systolic blood pressure may result. Clinical features may include tremor, anxiety, sweating, weight loss, diarrhoea, and heat intolerance. See the CKS topic on [Hyperthyroidism](https://cks.nice.org.uk/topics/hyperthyroidism/) for more information. - ** - Connective tissue disorders (scleroderma, systemic lupus erythematosus, polyarteritis nodosa). - Retroperitoneal fibrosis. - Obstructive sleep apnoea. See the CKS topic on [Obstructive sleep apnoea syndrome](https://cks.nice.org.uk/topics/obstructive-sleep-apnoea-syndrome/) for more information.

Answer 34

Drugs and other substances, including:** - Alcohol — misuse of alcohol may be the most common individual secondary cause of hypertension. Features include variable hypertension that is resistant to commonly used drugs and that disappears within a week or two of complete abstinence. - Ciclosporin. - Cocaine and other substances of abuse. - Combined oral contraceptive. - Corticosteroids. - Erythropoietin. - Leflunomide. - Liquorice — present in some herbal medicines. - Nonsteroidal anti-inflammatory drugs. - Sympathomimetics — may be found in over-the-counter cough and cold remedies (for example ephedrine and phenylpropanolamine). - Venlafaxine. - **Other conditions, including:**

Answer 35

Hypertension may cause progressive retinal microvascular changes. These changes have been classified by the Keith-Wagener Barker (KWB) grades: Grade 1: Generalised arteriolar narrowing (silver wiring). Grade 2: Focal narrowing and arteriovenous nipping. Grade 3: Retinal haemorrhages, cotton wool spots (retinal nerve fibre layer micro-infarcts leading to exudation of axoplasmic materials). Grade 4: Papilloedema Grade may indicate malignant hypertension requiring admission and immediate management. Recently there has been a move away from the KWB grades with a new three stage system proposed.

Answer 36

Hypertensive emergencies occur when high BP results in acute end-organ damage. The term malignant (or accelerated) hypertension is typically reserved for when papilloedema is present and is defined by NICE as: A BP >180/120 with signs of papilloedema and/or retinal haemorrhage. It is a severe condition resulting in neurological, renal and cardiac damage, requiring admission and immediate management. Treatment attempts to reduce BP over 24-48hrs. This is to prevent hypoperfusion. Changes may have occurred to autoregulatory mechanisms of blood pressure control. Therefore, a rapid reduction in blood pressure, even to normal levels, may result in profound organ hypoperfusion. Therapies include: ``` IV Nitroprusside (a nitric oxide releasing drug), labetalol and glyceryl trinitrate infusions are options. Phentolamine (alpha-adrenergic antagonist) also used in phaeochromocytoma crisis. ```

Answer 37

Patients < 80 years: clinic BP < 140/90 mmHg / ABPM < 135/85 mmHg Patients ≥ 80 years: clinic BP < 150/90 mmHg / ABPM < 145/85 mmHg Those with renal disease and proteinuria or diabetes should target a BP of < 130/80 mmHg.

Answer 38

Management of hypertension is based upon NICE guidelines. Modifiable risk factors Lifestyle modification & patient education are important in treating hypertension. Offer advice that targets the patient's modifiable risk factors. Discourage excessive caffeine and alcohol, if appropriate offer smoking cessation advice. Consider the need for anti-platelets or a statin. Whom to treat If clinic BP < 140/90 mmHg or ABPM < 135/85 mmHg, check BP at least every 5 years or more often if clinic BP close to 140/90 mmHg. If evidence of end-organ damage, consider other causes. Antihypertensive drug therapy is initiated in patients: Aged < 80 years with stage 1 hypertension and with one of the following; end organ damage, cardiovascular disease, renal disease, diabetes or 10-year cardiovascular risk ≥10%. of any age with stage 2 hypertension of any age with stage 3 hypertension (consider immediate treatment) Consider treatment in patients > 80 years old with stage 1 hypertension if clinic BP is > 150/90 mmHg. However, take into account frailty and co-morbidities. Patients < 60 years with stage 1 hypertension can be considered for antihypertensive therapy even if the 10-year cardiovascular risk < 10%. Specialist assessment Patients with stage 3 hypertension (≥ 180/120 mmHg) should be referred for same-day specialist assessment if any features of accelerated hypertension are identified: New onset confusion Chest pain Signs of heart failure (e.g. shortness of breath, fluid overload) Acute kidney injury Papilloedema Retinal haemorrhage In addition, any patient with suspected phaeochromocytoma needs same day assessment. If none of these features are present, patients should be urgently assessed for end-organ damage. If present, treatment should be considered immediately before ABPM/HBPM. If absent, blood pressure should be reviewed within 7 days in clinic. Any patient aged < 40 years should be considered for specialist assessment to exclude a secondary cause of hypertension.

Answer 39

ACE inhibitors- Cough Hyperkalaemia,Angioedema Bendroflumethiazide- Gout Hypokalaemia Hyponatraemia Impaired glucose tolerance Calcium channel blockers Headache Flushing Ankle oedema Beta-blockers Bronchospasm (especially in asthmatics) Fatigue Cold peripheries Doxazosin Postural hypotension

Answer 40

Orthostatic (postural) hypotension is an excessive fall in blood pressure (BP) when an upright position is assumed. The consensus definition is a drop of > 20 mm Hg systolic, 10 mm Hg diastolic, or both. Symptoms of faintness, light-headedness, dizziness, confusion, or blurred vision occur within seconds to a few minutes of standing and resolve rapidly on lying down. Some patients experience falls, syncope, or even generalized seizures. Exercise or a heavy meal may exacerbate symptoms. Most other associated symptoms and signs relate to the cause.

Answer 41

Antipyschotic Antidepressants Anti hypertension-ACEI,beta blocker leva dopa

Answer 42

Phaeochromocytoma is a rare catecholamine secreting tumour. About 10% are familial and may be associated with MEN type II, neurofibromatosis and von Hippel-Lindau syndrome Basics bilateral in 10% malignant in 10% extra-adrenal in 10% (most common site = organ of Zuckerkandl, adjacent to the bifurcation of the aorta) ``` Features are typically episodic hypertension (around 90% of cases, may be sustained) headaches palpitations sweating anxiety ``` Tests 24 hr urinary collection of metanephrines (sensitivity 97%*) this has replaced a 24 hr urinary collection of catecholamines (sensitivity 86%) Surgery is the definitive management. The patient must first however be stabilized with medical management: alpha-blocker (e.g. phenoxybenzamine), given before a beta-blocker (e.g. propranolol)

Answer 43

AKI may be classified by a number of systems including RIFLE and KDIGO. A number of different staging systems have been proposed to help grade the severity of AKI including the ‘RIFLE’ criteria, ‘AKIN’ criteria and more recently the ‘Kidney Disease: Improving Global Outcomes’ (KDIGO) criteria. Based on the KDIGO criteria, an AKI is defined by one of the following parameters: An increase in serum creatinine by ≥ 26.5 micromol/L within 48 hours An increase in serum creatinine to ≥ 1.5 times baseline within 7 days Urine output < 0.5 mL/kg/hr for six hours

Answer 44

``` Risk factors There are a number of risk factors that increase the likelihood of developing an AKI during hospital admission. Age (> 65 years old) History of AKI CKD Urological history (e.g. stones) Cardiac failure Diabetes mellitus Sepsis Hypovolaemia Nephrotoxic drug use Contrast agents ``` ``` Patients usually present with clinical features of hypovolaemia & dehydration. Reduced capillary refill time Dry mucous membranes Reduced skin turgor Thirst Dizziness Reduced urine output Orthostatic hypotension It is important to consider features associated with fluid loss including excessive sweating, vomiting, diarrhoea and polyuria. In elderly patients, there may also be evidence of confusion. ``` In patients with renal hypoperfusion in the context of hypervolaemia (e.g. cardiac failure), it is important to assess for fluid overload. ``` Ankle swelling Orthopnoea Paroxysmal nocturnal dyspnoea Dyspnoea Raised JVP Ascites Intrinsic renal ``` The clinical presentation of intrinsic renal AKI is dependent on the specific aetiology. Patients with ATN will demonstrate features consistent with the underlying aetiology. Those with intrinsic glomerular pathology may present with features of nephritic syndrome (e.g. haematuria, proteinuria, oliguria and hypertension) or nephrotic syndrome (e.g. heavy proteinuria, hypoalbuminaemia and oedema). Patients with a tubulointerstitial disease (e.g. acute interstitial nephritis) may complain of arthralgia, rashes and fever. Eosinophilia is frequently seen. Post-renal The clinical features of post-renal AKI depend on the site, chronicity and laterality (unilateral or bilateral) of the obstruction. Patients with urinary stones may present with classical loin-to-groin pain, haematuria, nausea and vomiting. Those with prostatic problems may have lower urinary tract symptoms (e.g. dysuria, frequency, terminal dribbling, hesitancy). Obstruction at the bladder neck might be associated with a palpable bladder and a tender suprapubic area.

Answer 45

anagement The management of an AKI should involve regular assessment and monitoring, controlling volume dysregulation and correcting electrolyte abnormalities and metabolic acidosis. Principles of management Management is guided by the underlying cause. Here we will discuss the general principles of management that can be applied to most cases of AKI. Patients can be staged according to the KDIGO criteria. It is suggested that patients who have stage 3 AKI or a suspected diagnosis that may require specialist intervention (e.g. glomerulonephritis, systemic vasculitis), be discussed with a nephrologist within 48 hours of detection. Patients with post-renal AKI may require discussion with a urologist. Regular assessment and monitoring Regular assessment of the patients' fluid status should be completed including monitoring their urine output, which may require a urinary catheter and daily weights. A baseline creatinine should be recorded and serial U&Es taken daily, increased to twice daily in more severe cases. Nephrotoxic drugs should be stopped (e.g. ACEi, NSAIDs, spironolactone) and regular prescriptions should be altered to reflect the change in creatinine clearance. Volume dysregulation If patients are hypovolaemic then intravenous fluids should be prescribed. The amount and type of fluids will depend on the clinical status of the patient. If the patient is hypervolaemic they may require fluid restriction +/- the use of diuretics. Diuretics (e.g. furosemide) should be used carefully in renal impairment as they can be nephrotoxic. Electrolyte abnormalities Severe hyperkalaemia, variably defined as >6.5 or 7 mmol/L, is a medical emergency. The management of hyperkalaemia is critical to avoid potential life-threatening arrhythmias. It involves: Protection of the myocardium: 10ml of 10% calcium gluconate. Reduce extracellular potassium: aim is to drive potassium into the intracellular compartment. Insulin (e.g 10 units ACTRAPID in 100ml 20% dextrose) and beta agonists (e.g. 2.5mg nebulised salbutamol) are given. Additional: stop or adjust potassium-sparing or potassium-containing medications. Resins can reduce potassium absorption but these take hours/days to have effect. Other electrolyte problems include hypocalcaemia and hyperphosphataemia. Metabolic acidosis The handling of acid-base is impaired in the setting of AKI due to a reduction in the GFR. This can results in a metabolic acidosis. Depending on the severity of acidosis and associated clinical state, choices for management involve the use of sodium bicarbonate or dialysis. Complications The major complications that can occur in association with AKI include hyperkalaemia, fluid overload, metabolic acidosis and uraemia. The development of uraemic complications (e.g. encephalopathy, pericarditis), hyperkalaemia, fluid overload or metabolic acidosis that are refractory to medical therapy warrant urgent dialysis. A useful mnemonic for assessment and management of any patient presenting with an acute kidney injury. RENAL DRS 26 mnemonic ``` R-record baseline creatinine E-Exclude obstruction N-Stop nephrotoxic drugs A-Assess fluid status L-losses and catheterisation D-Dipstick R-Review meds S-Renal screen 26-Greather than 26 rise in creatinine ```

Answer 46

Major causes include: ``` Hypertensive nephropathy Diabetic nephropathy Glomerulopathties Inherited kidney disorders (e.g. PCKD) Ischaemic nephropathy (e.g. vascular disease) Obstructive uropathy Tubulointerstitial diseases Medications ```

Answer 47

Clinical features Patients are generally asymptomatic with CKD, but start to develop non-specific symptoms at more advanced stages (e.g. eGFR < 45ml/min). It is always important to look for evidence of an underlying cause of CKD (e.g. large bilateral abdominal masses could be suggestive of PCKD). Symptoms ``` Frequently asymptomatic in early stages Anorexia & nausea Fatigue & weakness Muscle cramps Pruritus Dyspnoea Oedema Signs ``` ``` Pallor (secondary to anaemia) Hypertension Fluid overload (e.g. raised JVP, peripheral & pulmonary oedema) Skin pigmentation Excoriation marks Peripheral neuropathy ```

Answer 48

Indications Unexplained hematuria, proteinuria, AKI ,glomerular disease Contraindications Absolute-Clotting abnormality ,uncontrolled HTN, skin site infection Relative-Uncoperative patient, small kidney solitary kidney,Anatomic abnormality

Answer 49

The principles of CKD management are to treat the underlying cause, prevent or slow progression (e.g. renoprotective therapy), treat associated complications and plan for RRT. Management of chronic kidney disease (CKD) Renoprotective therapy Renoprotective therapy is aimed at slowing the progression of CKD, independent of the aetiology. Renoprotective therapy is centered around blood pressure control and reducing proteinuria. Specific blood pressure targets depend on whether CKD is secondary to diabetes and the presence of proteinuria. A standard BP target is < 130/80 mmHg if the patient is diabetic or has albuminuria. Therapy to control BP utilises ACE inhibitors and angiotensin receptor antagonists (both renin-angiotensin system antagonists). These drugs are both antihypertensive and antiproteinuric. Renin-angiotensin system antagonists should be offered to patients who are: Diabetic and have an ACR of 3 mg/mmol or more Hypertensive and ACR of 30 mg/mmol or more ACR > 70mg/mmol independent of CVS disease Outside of these parameters, hypertension should be treated in accordance with the usual NICE hypertension guidance (typical target BP < 140/90 mmHg). Other therapies to consider include: Statin therapy Smoking cessation Protein restriction: now not routinely recommendated as lack of quality evidence (discussed in the renal association practice guidelines) Antiplatelets for secondary prevention of CVS disease Treating complications A number of important complications develop as a consequence of CKD, which include anaemia, hyperkalaemia, mineral and bone disorders, fluid overload and acidosis. The management of mineral and bone disorders requires management of the underlying biochemical abnormalities. Hypocalcaemia: dietary supplements and calcitriol. Hyperphosphataemia: dietary restriction and phosphate binders. Hyperparathyroidism: calcimimetics or surgery. Fluid overload In the presence of significantly reduced GFR, the kidneys are unable to adequately controlled fluid volume. This leads to hypervolaemia and patients may have evidence of peripheral oedema, ascites, raised JVP, gallop rhythm and bilateral pleural effusions. Fluid overload can be managed with a combination of fluid restriction, reduced sodium intake and the use of oral diuretics (e.g. furosemide). It is still important to assess patients for other potential causes of anaemia (e.g. iron-deficiency, folate deficiency), which can subsequently be corrected. The main management for anaemia in CKD is the use of erythropoietin-stimulating agents (ESA) such as epoetin alfa. Hyperkalaemia The ability of the kidneys to maintain adequate acid-base homeostasis and electrolyte balance diminishes with worsening renal function. Many medications, including NSAIDs and potassium-sparing diuretics, may worsen hyperkalaemia. Furthermore, uncontrolled metabolic acidosis may also worsen potassium handling. Acute rises in potassium should be managed as a medical emergency. This involves stabilisation of the myocardium (with calcium gluconate) and driving potassium into the intracellular compartment (with insulin/dextrose). Chronic elevations in serum potassium can be managed with low potassium diets, potassium-binding resins and correction of acidosis. Acidosis Patients with CKD have an increased tendency to retain hydrogen ions because of abnormalities in their acid-base homeostasis. This leads to low bicarbonate levels and management generally involves the use of oral sodium bicarbonate therapy. Renal replacement therapy Haemodialysis, peritoneal dialysis and renal transplant are all forms of RRT that are indicated for ESRD. Haemodialysis-hypotension,disequilibrium syndrome, allergy Peritoneal- Continuous and Automated Complications-SBP

Answer 50

Bone pathology associated with cad Osteotitis fibrosa cystica Osteomalacia Adynamic bone disease-no bone turnover(PTH suppression)

Answer 51

1) Aetiology-HTN,DM,Glomerular disease 2) Plan and care-transplant,dialysis 3) Access -fistula,peritoneal,tunneled catheter 4) Frequency and last session 5) Units-last seen, current treatment, complications

Answer 52

Recall pathology various factors cause vascular injury leading to reduce NO and increase endothelin reducing vasodilation and increasing pressure Defined as mean pulmonary artery pressure (mPAP) ≥ 20mmHg at rest (measured by right heart catheterisation) Considered severe when: mPAP ≥35 mmHg mPAP ≥20 mmHg + elevated right atrial pressure +/- cardiac index <2L/min/m2 Classification ``` Group 1: Pulmonary Arterial Hypertension (PAH) with Pulmonary Artery Occlusion Pressure <15mmHg Idiopathic PAH Hereditary PAH Drug and toxin-induced PAH PAH associated with Connective tissue disease HIV infection Portal hypertension Congenital Heart Disease Schistosomiasis ``` Group 2: Pulmonary Hypertension due to left heart disease Heart failure with preserved ejection fraction Heart failure with reduced ejection fraction Valvular heart diseases Group 3: Pulmonary Hypertension due to lung diseases/ hypoxia Obstructive lung disease Restrictive lung disease Other lung disease with mixed restrictive/ obstructive pattern Developmental lung disorders Group 4: Pulmonary Hypertension due to pulmonary artery obstructions Chronic thromboembolic pulmonary hypertension (CTEPH) Other pulmonary artery obstructions Group 5: Pulmonary Hypertension with unclear/ multifactorial mechanism Systemic and metabolic disorders Others Complex congenital heart diseases

Answer 53

Risk factors Family history of pulmonary arterial hypertension Congenital heart disease Connective tissue disease (systemic sclerosis, SLE) Drugs and toxins Aminorex, Methamphetamine, Fenfluramine Aminorex =a type of SSRI, stimulates weight loss Fenfluramine= appetite suppressant Human Immunodeficiency Virus (HIV) Mechanism not known Portal hypertension Genetics-Abnormal BMPR2 gene symptoms and signs ``` Shortness of breath Chest pain Dizziness Syncope Fatigue Oedema Dry cough Raynaud’s phenomenon ``` ``` Skin- Telangiectasias, Raynaud’s phenomena, Sclerodactyly Increased jugular venous pressure (JVP) Hepatojugular reflux Peripheral oedema +/- ascites Heart sounds: Accentuated split S2 Third heart sound present Tricuspid regurgitation- heard best at left lower sternal border ```

Answer 54

Diagnosis-Echo-right heart catheterisation check notion for pathway Management depend on classification type 1-pulmonary vasodilators,prostonoids(illoprost),ccb,long term anticoagulation like wafarin check notion lung transplant New York Heart Association (NYHA) functional class III or IV Mean right atrial pressure >10mmHg Mean pulmonary arterial pressure >50 mmHg Failure to improvefunctionally despite medical therapy Rapidly progressive disease

Answer 55

Large central pulmonary arteries peripheral pruning Enlarged right heart

Answer 56

Indications Failure of medical and surgical improvement of disease Less than a 2 year expected survival from disease Progressive exercise intolerance CO2 retention Increased O2 requirements Right Heart Failure ``` Contraindictions Incurable Malignancy Old Age – >69 Active or incurable infection – HIV, Hep C… Other major organ system damage (kidney, liver) Morbid obesity Alcohol, smoking or drug abuse Corticosteroid Therapy Previous CT surgery (case by case) ```

Answer 57

Follow up Lung Biopsies done at 2 weeks, 4-6 weeks and 12 weeks, 6 months, and then yearly Acute Rejection usually happens within the first year Occurs in 36% of transplants Diagnosis includes: ⚫ Fever, dyspnea, impaired gas exchange (↓ PaO2), ↓ forced expiratory volume (airway flow) complications Infections are the leading cause of morbidity and mortality in lung transplants Bacterial, Viral, and Fungal Infections Infection rate in lung tx is higher than any other tx Due to airway colonization having direct exposure to the lung allograft ⚫ And the lack of the cough relfex Bacterial infections often originate from the donor lungs Recipient can provide their own infections pre-op, common in Cystic Fibrosis patients ``` Acute Bleeding acute rejection REPERFUSION INJURY electrolyte abnormalities arrhythmia kidney problems ``` ``` Chronic chronic rejection skin cancers DM HTN Arrthymias CKDA ```

Answer 58

Restricted to patients with: (mostly) Congenital heart disease’s with Eisenmenger’s Syndrome (#1 indication for HLT)- 35% ⚫ Trunchus arteriosus, pulmonary atresia, HLHS Idiopathic pulmonary arterial HTN- 25% Cystic Fibrosis- 14% ``` Complications HTN- 88%% Renal Dysfunction- 28% Hyperlipidemia- 66% Diabetes- 21% Bronchiolitis Obliterans- 27% Coronary Artery vasculopathy- 8% Survival Rates: 72% at 3 months 64% at 1 year ```

Answer 59

Manufacturing of fluorescent light tubes, ceramics, electronics, aerospace industries etc Workers at risk: Processes generating airborne beryllium particles Acute Chronic- Granulomatous inflammatory disorder Very similar to sarcoidosis ``` Clinical features Insidious onset Symptoms Dyspnoea on exertion Cough Fatigue Crackles upon auscultation Anorexia and weight loss Fever Chest pain ``` Lab History of beryllium exposure Positive lymphocyte proliferation test (LPT) Peripheral blood/ bronchoalveolar lavage LPT to confirm sensitisation to beryllium Transbronchial biopsy of lung tissue to confirm presence of disease Presence of epithelioid granulomas & mononuclear infiltrates in absence of infections in lung tissues

Answer 60

Inhalation of silicon dioxide (silica) Silica major component of rock and sand Key elements: History of silica exposure sufficient to cause degree of illness, with appropriate latency period from time of first exposure Absence of another diagnosis more likely to be responsible for observed abnormalities Acute silicosis Intense exposure to fine dust of high silica content over several months Subacute/ Accelerated silicosis Shorter duration, heavier exposures (2-5 years) compared to chronic simple silicosis Chronic simple silicosis Most common form >10 years exposure to dust <30% quartz (Silicone dioxide SiO2) CXR findings Hallmark: Silicotic nodules/ islet in pulmonary parenchyma and hilar lymph nodes Nodules appear as small, round opacities (<10mm) in bilateral upper lung zones on chest x-ray Calcification of lesions forming “egg-shell” appearance Upper lobes fibrosis Signs and symptoms Few symptoms and signs Pulmonary function test Usually normal Occasionally mild restrictive and decreased lung compliance Disease progresses to complicated silicosis as fibrosis progressively develops in upper lobes

Answer 61

Small, silicotic nodules coalesce into larger, fibrotic masses Tend to occur in upper lung fields May obliterate blood vessels and bronchioles Distort lung architecture Leads to respiratory insufficiency

Answer 62

Lung tissue reaction to presence of dust accumulation in lungs Essential factors for clinical pneumoconiosis: Exposure to specific substance: Silica and asbestos: Potent biological effect Coal: May accumulate to considerable amounts, but minimal tissue response Size of particles between 1-5 μm Commonly retained in lungs Exposure for sufficient length of time ~10 years

Answer 63

Complications Susceptible to mycobacterial and fungal diseases (e.g. cryptococcosis) Silicotuberculosis Silica is cytotoxic to alveolar macrophages Patients at increased risk of developing TB Autoimmune disorder: Rheumatoid arthritis Scleroderma Malignancy Management No definitive treatment Most important aspect: Prevention from silica exposure in work environment Advice change of occupation to avoid further silica dust exposure Advice smoking cessation Control and prevent development of TB in patients Tuberculin skin test/ interferon-γ assay test to identify TB status Lung lavage to remove silica from alveoli Consider lung transplant in acute and accelerated silicosis

Answer 64

Rheumatoid arthritis + pneumoconiosis Manifest as intrapulmonary nodules Appear homogenous and well-defined on chest X-ray Lesions grow rapidly, cavitate, and might produce pneumothorax Compared to silicosis/ CWP where nodules appear over a period of time

Answer 65

Asbestos widely used to construct ceiling, walls and flooring of houses/ buildings Provide insulation and fire protection Latency period Several years before pleural \Very high incidence before 1980s Asbestos widely used to construct ceiling, walls and flooring of houses/ buildings Provide insulation and fire protection Latency period Several years before pleural thickening develops >20 years for fibrosis & plaque Parenchymal asbestosis Diffuse interstitial fibrosis with restrictive pattern on pulmonary function test Impaired gas exchange in alveoli Presents with progressive exertional dyspnoea and fatigue Takes >10 years for radiographic changes to develop Asbestos related pleural abnormalities Types of abnormalities: ``` Pleural plaques Benign asbestos pleural effusion Diffuse pleural thickening Rounded atelectasis Mostly asymptomatic Some patients may develop progressive dyspnoea, intermittent chest pain, cough ``` ``` CXR Small, irregular, oval opacities Diffuse interstitial fibrosis “Shaggy heart border” sign Cardiac silhouette ill-defined on chest radiograph Implies pleural ```

Answer 66

Malignancy/ thickening at pleural lining of lungs Usually linked to chronic asbestos exposure Symptoms: Normally asymptomatic until advance stages Dyspnoea, chest pain, fatigue CXR Mass at mid zone of left lung (pushes trachea towards right) Pleural thickening (Increased radiopacity at pleura linings ) Pleural effusion (Meniscus sign: blunted costophrenic angle

Answer 67

``` Obesity (Strongest Risk Factor) Male Middle age (30-50 years old) Hypothyroidism Acromegaly Use of sedatives/ narcotics/ alcohol Smoking ```

Answer 68

``` Increased risk of vascular diseases: Systemic hypertension Pulmonary hypertension (due to hypercapnia) Arrhythmia Nocturnal bradycardia during apnoea, tachycardia upon resolution Myocardial infarction Heart failure Stroke Sudden death ``` Excessive daytime sleepiness Reduced concentration in daily activities Road-traffic accidents due to driver sleepiness (risk 7x greater) Repetitive hypoxemia and hypercapnia Reduced airflow into lungs Subsequent bodily oxygen desaturation Chemoreflex mediated sympathetic activation Increased sympathetic nerve activity + increased catecholamine Increased cardiac output & vasoconstriction BP could rise to 220/130mmHg during apnoea Diastolic nocturnal hypertension Loss of nocturnal dipping of blood pressure OSA Cardinal Symptoms (3S): Snoring Sleepiness Sleep Apnoea Episodes

Answer 69

Epworth sleep scale Self-administered 8-question questionnaire Respondents asked to rate from 0-3 on their usual chance of dozing off while doing activities listed on questionnaire Scores: 0-10: normal daytime sleepiness 11-12: mild excessive daytime sleepiness 13-15: moderate excessive daytime sleepiness 16-24: severe excessive daytime sleepiness ``` Examination Inspection Obesity Micrognathia/ retrognathia (small, receding lower jaws) Macroglossia (enlarged tongue) Neck size >17 inches Nasal congestion/ nasal polyps Tonsillar hypertrophy Adenoid enlargement ``` Bedside Blood pressure Assess systemic hypertension (complications of OSA) ECG Rule out arrhythmias, myocardial infarction etc (complications of OSA) Arterial blood gas Look for pO2 and pCO2 (patient with OSA experience hypoxemia and hypercapnia) ``` Bloods Full blood count Patient might have polycythaemia secondary to chronic hypoxemia Thyroid function test Hypothyroidism- risk factor of OSA ``` Imaging Echocardiography Assess presence of left ventricular hypertrophy (complication of OSA) CT/MRI Cephalometric analysis Look at structure of airways, adenoids, tongue etc Diagnosis made through overnight sleep study(Polysonography) Overnight sleep study of varying complexity could be performed Depending on patient preference and local arrangements Inpatients At home

Answer 70

Acute limb ischaemia is defined as severe, symptomatic hypoperfusion of a limb occurring for <2 weeks. Even though the definition talks of 2 weeks, it is a surgical emergency and needs to be corrected as soon as possible, ideally within 4-6 hours. The 6Ps of acute limb ischaemia ``` Pulseless Painful Pale Paralysis Paraesthesia Perishingly cold In real life if the limb has lost motor and sensory function then it is almost certaintly unsalvageable so these signs are not particularly useful if you want to try and save the limb! ``` Management As in all emergencies, approach using the DR ABCDE algorithm: As part of B, administer oxygen. As part of C, administer intravenous fluids and analgesia. Take bloods for FBC, U&E, group and save, and clotting. ECG is important to see whether the patient is in atrial fibrillation (this suggests an embolic cause). The next steps are to urgently inform vascular surgery. The patient should be kept nil by mouth in preparation for surgery. Intravenous heparin (to prevent thrombus propagation) may be administered (typically after senior review). Definitive management depends on whether there is complete or incomplete limb ischaemia, and whether the cause is thrombotic or embolic. Management of thrombotic causes In thrombotic causes: If ischaemia is incomplete (and the limb is likely to remain viable for 12-24 hours), patients should have angiography to map the occlusion site and plan intervention. Endovascular procedures may be an option (such as angioplasty, thrombectomy, or intra-arterial thrombolysis). If ischaemia is complete patients must be urgently taken to theatre for bypass surgery. Angiography and thrombolysis will delay management. Management of embolic causes In embolic causes: the leg is typically threatened and immediate embolectomy is required. Angiography can be used to confirm the adequacy of the procedure. If embolectomy fails, on-table thrombolysis may be considered. Note that if the limb is non-viable amputation may be required.

Answer 71

ny patient suspected or diagnosed as having PAD should have a full cardiovascular risk assessment including blood pressure, FBC, blood glucose, lipids and electrocardiogram. Other specific investigations include: Ankle-Brachial Pressure Index (ABPI) is a simple, first-line investigation for peripheral artery disease (PVD) that can be performed on almost all patients. It is performed by using a doppler probe for find the systolic brachial blood pressures of the arms and comparing them to the ankle blood pressures in the feet. The ABPI is calculated as follows: Brachial pressure (on side of interest)/Ankle pressure (on side of interest) Interpretation of ABPI Interpretation is as follows: ``` More than 1.2: abnormal thickening of vascular walls (think diabetes) 0.9 - 1.2: Normal 0.8 - 0.9: Mild disease 0.5 - 0.8: Moderate disease Less than 0.5: Severe disease Imaging investigations ``` A normal ABPI in a diabetic patient CANNOT exclude peripheral vascular disease and they will almost certainly need further investigation. First line-Duplex arterial ultrasound - for those who might be suitable for revascularisation. Can determine the site, severity and length of stenosis. MR arteriogram - used for those who are candidates for revascularisation CT arteriogram - used in those unsuitable for MR Digital subtraction angiography - usually performed at the time of intervention or for monitoring disease

Answer 72

Management of the chronically ischaemic leg (non-surgical) Conservative measures include risk factor modification. This involves offering referral for a supervised exercise programme. Advise should be given on smoking cessation and weight management. Medical management involves: A. Managing cardiovascular risk: Antiplatelet therapy: with clopidogrel 75mg once daily. Aspirin is prescribed only if clopidogrel is not tolerated or contraindicated. Lipid lowering therapy: with atorvastatin 80mg once nightly. In diabetics, glycaemic control should be optimised. High blood pressure should be managed appropriately. B. Managing pain with appropriate analgesia: Naftidrofuryl oxalate is a vasodilator which can alleviate pain in peripheral vascular disease. It should only be prescribed if supervised exercise is ineffective and the patient does not want to be referred for angioplasty or bypass surgery. Management of the chronically ischaemic leg (surgical) Patients with intermittent claudication should be referred for endovascular revascularisation or surgical revascularisation when risk factor modification has been introduced and supervised exercise programme has not led to symptom improvement. For critical limb ischaemia (where there is rest pain, tissue loss, and ankle artery pressure of <50 mmHg) patients should be urgently referred to the vascular multidisciplinary team for endovascular revascularisation or surgical revascularisation. Endovascular methods are recommended for small discrete stenosis. Surgical bypass is recommended for larger more extensive stenosis. Amputation may be required if there is: critical limb ischaemia unsuitable for other interventions, intractable pain, an unresolving ulcer, or severe loss of function.

Answer 73

``` Hypertension Atherosclerosis-Atherosclerotic ulcer Genetical-Marfan's,Ley's Dietz,Ehlers-Danlos,Biscuspid aortic valve,Herditary thoracic AAA Coarctation of aORTA Turner's TOF Trauma-stent.ect Pregnancy Inflammatory-Takayasu ```

Answer 74

Most aneurysms are asymptomatic. They can present with abdominal mass (which is usually pulsatile and expansile) Screening and repeat screening principles In the UK, screening is offered at age 65 using abdominal ultrasound scan. If small AAA (3-4.4cm) – offered yearly repeat ultrasound If medium AAA (4.5-5.4cm) – offered repeat ultrasound every 3 months If large AAA (>5.5cm) – surgery generally recommended. Management Surgical options: The two main surgical options are open repair or Endovascular Aneurysm repair (EVAR). The indications for repair are size >5.5cm or rapid expansion. Rapid expansion is defined as increase in diameter >5mm over a 6 month period or >10mm over one year. These limits have been developed due to clinical evidence which balances the risk of surgery vs the risk of aneurysm rupture. It is very uncommon for aneurysms below 5cm to rupture.

Answer 75

``` Associations hypertension: the most important risk factor trauma bicuspid aortic valve collagens: Marfan's syndrome, Ehlers-Danlos syndrome Turner's and Noonan's syndrome pregnancy syphilis Amphetamine use ``` Features: chest pain: typically severe, radiates through to the back and 'tearing' in nature pulse deficit weak or absent carotid, brachial, or femoral pulse variation (>20 mmHg) in systolic blood pressure between the arms(radio-radial and radio femoral delay)CT angiogram is used to diagnose dissection but other investigations can suggest the diagnosis and/or its complications: Complications Complications of backward tear aortic incompetence/regurgitation MI: inferior pattern is often seen due to right coronary involvement Complications of a forward tear unequal arm pulses and BP stroke renal failure Death due to internal haemorrhage Rupture Cardiac tamponade Stroke Limb ischaemia Mesenteric ischaemia

Answer 76

Inx ECG - May show ischaemia in specific territories if dissection extends into coronary arteries. Echocardiogram - May demonstrate pericardial effusion and aortic valve involvement. Chest x-ray - May show a widened mediastinum Bloods: Troponin may be raised D-dimer may be positive Prognosis Prompt diagnosis and treatment is required as rupture carries an 80% mortality rate. Initial management Resuscitation if necessary Cardiac monitoring Strict blood pressure control (e.g. IV metoprolol infusion) Definitive management Depends on the type of dissection Type A: Usually requires surgical management (e.g. aortic graft) Type B: Normally managed conservatively with blood pressure control. If there is evidence of end organ damage then endovascular/open repair may be performed. Stanford classification type A - ascending aorta, 2/3 of cases type B - descending aorta, distal to left subclavian origin, 1/3 of cases DeBakey classification type I - originates in ascending aorta, propagates to at least the aortic arch and possibly beyond it distally type II - originates in and is confined to the ascending aorta type III - originates in descending aorta, rarely extends proximally but will extend distally Type A surgical management, but blood pressure should be controlled to a target systolic of 100-120 mmHg whilst awaiting intervention Type B* conservative management bed rest reduce blood pressure IV labetalol to prevent progression

Answer 77

Definition Buerger's disease is a non-atherosclerotic vasculitis caused by occlusion in small and medium-sized arteries. Epidemiology It is most common in young male smokers of Mediterranean and Middle Eastern origin. Clinical Features It typically presents as an acutely ischaemic limb, without a background of peripheral claudication. Investigations Investigations are aimed at excluding differentials (such as atherosclerotic disease and autoimmune disease). Arterial Doppler will confirm the absence of peripheral pulses in the affected limb. Further imaging (such as with arterial duplex or CT/MR angiography) will show non-atherosclerotic occlusion. Martorell's sign on arterial duplex describes the 'corkscrew'-shaped collateral vessels characteristic of Buerger's disease. Management Management is with smoking cessation ± vasoactive medication (such as nifedipine). If there is critical ischaemia the patient requires hospital admission, vasoactive medication and debridement of gangrenous tissue.

Answer 78

aynaud's phenomenon is characterised by an exaggerated vasoconstrictive response of the digital arteries and cutaneous arteriole to the cold or emotional stress. It may be primary (Raynaud's disease) or secondary (Raynaud's phenomenon). Raynaud's disease typically presents in young women (e.g. 30 years old) with bilateral symptoms. ``` Secondary causes of Raynaud's phenomenon connective tissue disorders scleroderma (most common) rheumatoid arthritis systemic lupus erythematosus leukaemia type I cryoglobulinaemia, cold agglutinins use of vibrating tools drugs: oral contraceptive pill, ergot cervical rib ``` ``` Factors suggesting underlying connective tissue disease onset after 40 years unilateral symptoms rashes presence of autoantibodies features which may suggest rheumatoid arthritis or SLE, for example arthritis or recurrent miscarriages digital ulcers, calcinosis very rarely: chilblains ``` Management all patients with suspected secondary Raynaud's phenomenon should be referred to secondary care first-line: calcium channel blockers e.g. nifedipine IV prostacyclin (epoprostenol) infusions: effects may last several weeks/months

Answer 79

Marfan's syndrome is an autosomal dominant connective tissue disorder. It is caused by a defect in the FBN1 gene on chromosome 15 that codes for the protein fibrillin-1. It affects around 1 in 3,000 people. Features tall stature with arm span to height ratio > 1.05 high-arched palate arachnodactyly pectus excavatum pes planus scoliosis of > 20 degrees heart: dilation of the aortic sinuses (seen in 90%) which may lead to aortic aneurysm, aortic dissection, aortic regurgitation, mitral valve prolapse (75%), lungs: repeated pneumothoraces eyes: upwards lens dislocation (superotemporal ectopia lentis), blue sclera, myopia dural ectasia (ballooning of the dural sac at the lumbosacral level) The life expectancy of patients used to be around 40-50 years. With the advent of regular echocardiography monitoring and beta-blocker/ACE-inhibitor therapy this has improved significantly over recent years. Aortic dissection and other cardiovascular problems remain the leading cause of death however.

Answer 80

Diabetic-sensory drugs-sensory Alcohol-sensory CMT-mixed(Charcot-Marie-Tooth disease) CIDP-motor Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare type of autoimmune disorder. In an autoimmune disease, the body attacks its own tissues. In CIDP, the body attacks the myelin sheaths. If in doubt use Surgical sieve-Infection,Inflammation,Neoplasm,Vascula,trauma/structural,Neurodegenerative,hereditary,metabolic

Answer 81

Repetitive nerve stimulation show decrement in NMJ disorders like myasthenia gravis

Answer 82

Conservative: relaxation techniques, reduce caffeine Medical: propanolol, primidone Surgical: deep brain stimulation (only for very severe/refractory cases) ---

Answer 83

The most common cause of drug-induced movement disorders are dopamine receptor blocking agents. Antipsychotics, metoclopramide and prochlorperazine are prevalent examples that you will undoubtedly prescribe during your career. These medications can cause various movement disorders including tremor, neuroleptic malignant syndrome (covered in the next section), dystonia and parkinsonism. The exact pathophysiology of tardive dyskinesia in unclear. A common theory is that there is a dopamine hypersensitivity in the nigrostriatal pathway after chronic pharmacological blockage Treatment can be difficult and therefore prevention is crucial. Dopamine receptor blocking medications should be used in the lowest dose for the shortest time possible. Treatment involves withdrawing the offending agent and this may require an analysis of benefit vs. harm (e.g. if the antipsychotic is treating schizophrenia). There is usually a delay before improvement and changes can be irreversible. Tetrabenazine can be effective in some people who have not responded to treatment withdrawal.

Answer 84

Dopamine receptor blocking drugs can cause a severe neurological emergency called neuroleptic malignant syndrome (NMS). This can also be induced by sudden cessation of dopaminergic medications e.g. levodopa. NMS is a clinical diagnosis, supported by the diagnostic criteria below. NMS is characterised by **high temperatures, rigidity,** autonomic dysfunction and altered mental status (often agitated confusion). Patients may demonstrate hyporeflexia. A common scenario for this to occur would be with a patient already on an antipsychotic e.g. haloperidol (highest risk) who is then given a dopamine blocking antiemetic such as metoclopramide. The high temperature and altered mental state would make you think about infection but is important to take note of the patient's medications. **Rigidity, a new tremor and a raised CK** should make you think about NMS. The pathophysiology of NMS is thought to be due to the abrupt loss of dopaminergic activity in the nigrostriatal pathway and basal ganglia, with fever thought to be due to dopamine blockade in the hypothalamus (which plays a role in thermoregulation). Diagnosis-all there major criteria and at least 2 minor criteria Major-Exposure to dopaminergic drug, rigidity,hyperthermia minor-tachycardia,incotience,raised bp,CK **Treatment approach:** - Stop the dopamine blocking medication - Supportive care: IV fluids, correct metabolic abnormalities - Medications in severe cases: bromocriptine (a dopamine agonist, to increase dopaminergic activity) and dantrolene (muscle relaxant to reduce rigidity, acts by inhibiting inhibiting calcium release from the sarcoplasmic reticulum in muscle cells.)

Answer 85

Serotonin syndrome is another drug-induced syndrome that causes hyperthermia and neurological changes. In patients with polypharmacy you may need to differentiate this from NMS. Serotonin syndrome can be caused by prescription of multiple serotonergic drugs or medication overdose. This essentially leads to serotonin toxicity and hyperstimulation in the central nervous system. Serotonin syndrome can be caused by multiple classes of drugs that affect signaling in presynaptic and postsynaptic serotonergic neurons (in the raphe nuclei of the brainstem). The picture below demonstrates a serotonin synapse and how medications affect this. Approach to treatment: - Withdraw serotonergic agents - Supportive care: IV fluids, cooling - Medications in severe cases: Benzodiazepines can be used to reduce agitation and myoclonus. Cyproheptadine (a serotonin antagonist) is sometimes used but the evidence base for this is not strongly established.We can see that a lot of symptoms overlap with NMS.

Answer 86

We can see that a lot of symptoms overlap with NMS. Differentiating between the two conditions clearly begins with checking the patient's medications and any recent changes. If a patient is pharmacologically at risk of both, their neurological symptoms are most helpful in distinguishing between the two. ``` Serotonin syndrome More acute (<24hours) Serotonergic Increased: hyperreflexia, clonus, tremor Diarrhoea, increased bowel sounds ``` ``` NMS More gradual (days-weeks) Dopaminergic Decreased: rigidity, hyporeflexia Usually normal ```

Answer 87

Dystonia is caused by sustained or intermittent muscle contractions / spasms that often lead the patient to hold abnormal postures or positions. This frequently causes discomfort and pain for the patient. Dystonia can have a genetic cause or be acquired from mechanisms such as trauma, stroke and drug toxicity. We will look at drug induced hyperkinesia later in this tutorial. - **Focal:** one body part affected - **Segmental:** adjacent body parts affected - **General:** entire body affected Approach to management: - **Conservative:** education, relaxation, massage - **Medical:** A small % of patients respond to dopaminergic medication (e.g. levodopa). Benzodiazepines are also used. - **Surgical:** BoTox injection, especially useful in focal dystonia. Deep brain stimulation may be used in severe cases.

Answer 88

The huntingtin gene (on the short arm of chromosome 4) codes for the huntingtin protein. The specific pathology of the disease is not completely characterised but mutated huntingtin protein aggregates are found in the basal ganglia, specifically the dorsal striatum (caudate and putamen), and these areas show increased neuronal death rates. There is thought to be a toxic gain-of-function in the mutant huntingtin protein. A section of the genetic code for this protein has something called a trinucleotide repeat expansion. This is a repeating sequence of three nucleotides. In the case of huntingtin, this is a CAG repeat (which encodes glutamine and hence is known as a polyglutamine disease). Patients with 40 or more repeats will develop the disease (100% penetrance) but patients with 36-39 repeats show a reduced penetrance. 27-35 repeats are classified as in the 'intermediate CAG range' and less than this is normal. For example, if a patient has a repeat number of 40, they are certain to develop the disease (assuming they survive until disease onset). A patient with 36 repeats may or may not develop HD and a patient with fewer repeats than this will not There is a juvenile form, also known as the Westphal variant HD, due to a very large repeat count.

Answer 89

**How to confirm the diagnosis?** For HD, a trinucleotide cytosineadenosine-guanine (CAG) equal to or greater than 36 repeats is diagnostic **in the presence of characteris tic symptoms**. Caudate and putamen atrophy No disease modifying therapies are currently available for HD on the NHS. However, there is promising research, which you can read about in your "Future Treatment - Antisense Oligonucleotides" tutorial, that has the potential to drastically change our management of the disease. Current treatments include: - **Conservative:** Symptomatic / supportive therapy to alleviate the symptoms - **Medicine:** Anti-choreic medication – atypical antipsychotics, tetrabenazine - **Surgical:** Deep brain stimulation for pharmacological resistant chorea with significant disability Ultimately, there is no cure for HD at present and treatment revolves around supportive care (such as modifications in the patient's house by occupational therapists, physiotherapy, speech and language therapy and additional carers) and symptomatic relief. Tetrabenazine is approved for the treatment of chorea in HD. Antipsychotics can be used to treat psychiatric symptoms, as well as often also helping with chorea

Answer 90

3 stages-Early,middle,lates The initial symptoms occur more frequently between the ages of 30 and 50, although onset can range from childhood/adolescence (juvenile form, also known as the Westphal variant) to individuals older than 70 years of age. HD can present to the clinician with one of three symptom complexes classically described in this condition (motor/physical, cognitive, and neuropsychiatric/emotional) or in combination. The motor symptoms include chorea, dystonia, and tics. Motor Cognitive-Usually middle to late.Diffculty planning ,thinking and performing complicated tasks Behavioural-Irritabilty ,hypersexuality ,inhibition ,depression ,auditory hallucinations,apathetic towards the late stages

Answer 91

acute surgical decompression of his L4/5 disc prolapse causing Incomplete Cauda Equina Syndrome. If surgery is required, this should happen within the next 48 hours. Possible surgeries would be a laminectomy or discetomy. The surgeons may recommend the use of high dose steroids to reduced swelling and oedema around the site of nerve compression. The steps to take on the admissions ward are: - Adequate analgesia for pain control - Blood tests (including Group and Save and Coagulation) to prepare for surgery - Urethral catheter if in urinary retention or difficulty passing urine - Check if patient needs to be Nil By Mouth for surgery Monitoring for deterioration or development of urinary retention.

Answer 92

Patients may suffer long-term complications from Cauda Equina Syndrome, the risks of which are increased if they do not receive early and appropriate intervention. Surgery should happen within 48 hours of presentation if it is required. Patients may experience long-term issues with pain, reduced motor function, bladder/bowel disturbance and sexual dysfunction. Complete Cauda Equina Syndrome (with urinary retention) has worse long-term outcomes than Incomplete Cauda Equina Syndrome. Anyone with Incomplete Cauda Equina Syndrome should be carefully monitored whilst awaiting surgery for any developing/changing signs. Litigation for missed/delayed management of Cauda Equina Syndrome is common. Always ask your red flag symptoms, perform thorough examination, safety net the patient, and document your findings/discussion clearly!

Answer 93

Guillain-Barré syndrome Cauda-Equina syndrome Stroke (if unilateral, worth keeping in mind) Transverse myelitis Epidural abscess 'Off legs' (general reduced mobility)

Answer 94

Recent advances in genetic medicine have allowed for the development of new treatments for single gene disorders. This is in the form of a new class of drugs called anti-sense oligonucleotides (ASOs). These compounds bind to specific mRNAs and ultimately affect protein expression in various desired ways, dependent on the disease we are treating. Expanding on this video, the SMN protein is particularly important in promoting the survival of alpha motor neurons, which exit through the ventral roots of the spinal cord to directly innervate skeletal muscle and initiate contraction. In SMA the SMN1 gene is mutated or deleted homozygously in a way that ultimately results in insufficient levels of SMN protein. The SMN2 gene is a pseudogene copy of SMN1, which means that it is a mutated copy which produces little or no functional protein. In this case very little functional protein is produced. This is because a single nucleotide mutation in exon 7 of SMN2 leads to it being removed in the majority of mRNAs. This resultant protein is non-functional / rapidly degraded. Nusinersen is an ASO which binds to a complimentary sequence after exon 7 and causes mRNA processing to include this exon. Thus, functional SMN protein is produced. For many patients this leads to significant motor function and survival benefits. Expanding on this video, the SMN protein is particularly important in promoting the survival of alpha motor neurons, which exit through the ventral roots of the spinal cord to directly innervate skeletal muscle and initiate contraction. In SMA the SMN1 gene is mutated or deleted homozygously in a way that ultimately results in insufficient levels of SMN protein. The SMN2 gene is a pseudogene copy of SMN1, which means that it is a mutated copy which produces little or no functional protein. In this case very little functional protein is produced. This is because a single nucleotide mutation in exon 7 of SMN2 leads to it being removed in the majority of mRNAs. This resultant protein is non-functional / rapidly degraded. Nusinersen is an ASO which binds to a complimentary sequence after exon 7 and causes mRNA processing to include this exon. Thus, functional SMN protein is produced. For many patients this leads to significant motor function and survival benefits. So far, the most promising research has been undertaken with ASOs in patients with mutant SOD1 genes. Multiple point mutations in this gene have been found to be associated with FALS. However, the mechanism by which these mutations cause ALS is poorly characterised. Despite this results have been promising. At the time of writing there are ongoing clinical trials for SOD1 ASOs. As with Huntington's, the purpose of the ASO is to target mutant mRNA for degradation.

Answer 95

You can diagnose and **cure** this through a couple of manoeuvres: - Dix-Hallpike manœuvre is used to diagnose this (**D**iagnose and **D**ix-Hallpike both begin with **D**) - Eply manoeuvre can be used to knock the stones out of the semilunar canals to move to otolith out the semicircular canals The nystagmus in this case is torsional/rotational, which furthers point you to the patient having an inner ear cause for their dizziness. You can see this in the video above. Once diagnosed, you can do the Epley manoeuvre, which is essentially a series of movements designed to knock the otoliths out. Obviously you don't need to know these movements!

Answer 96

This is an inflammation of the peripheral vestibular system, commonly it follows a viral upper respiratory tract infection (like a cold!) - **Vestibular neuronitis:** Vertigo (much more common) - **Labyrinthitis:** Vertigo AND hearing loss Unlike BPPV the vertigo is constant rather than lasting a few seconds triggered by heading movements (although head turning usually does make it feel worse!). Onset is acute and usually lasts for around a week. The patient often feels awful, very nauseous/vomiting and not keen to put up with your head-spinning neurological examination. Always consider posterior circulation stroke or other acute neurological event as a differential for vertigo. Nystagmus can provide a good clue.

Answer 97

This is a **rare** condition caused by increased production of fluid in the inner ear. It's characterised by recurrent attacks of vertigo (lasting minutes-hours) and a feeling of aural fullness. The condition is associated with a fluctuating, often progressive sensorineural hearing loss and tinnitus. Meniere's disease is probably over diagnosed in the population. Vertigo is symptomatically managed with betahistine, but this is only a treatment for Meniere's disease **not all vertigo**.

Answer 98

Proprioception is the most important sensation for ensuring that we have good balance - you need to know where you are in space to move properly and keep yourself upright. Failing this, you then have to rely on your visual system to orientate you instead. This directly reflects in the presentation of someone who has damage to their proprioception pathways. They will be profoundly unsteady, will have a broad based, ataxic gait, and will be staring at their feet. The result is largely the same depending on where the lesion is: - Sensory neurones - alcohol, diabetes, Guillian-Barre - Dorsal root ganglion - Sjogren's, paraneoplastic syndrome - Dorsal column - Tabes dorsalis (syphilis), B12 deficiency

Answer 99

Romberg's sign is when someone becomes more unbalanced and may even fall over when their eyes are closed. This reflects that you need at least two of the three systems functioning to maintain balance: - Vestibular system - Proprioception - Visual system If you know the patient's vestibular system and visual system are working normally (which can be confirmed by examination), then you can localise the faulty system to proprioception. This can be due to an issue with peripheral sensory proprioception or the dorsal column (where the proprioception nerves travel along). Importantly it is **negative** (no change to dizziness level with eyes open/closed) ****in cerebellar causes of ataxia.

Answer 100

If patients have an ataxic gait, but the examination of their sensory system is unremarkable, then the root of their problem could be cerebellar. The gait is not particularly different than the ataxic gait seen in sensory dysfunction. As the cerebellum's usual function is to contribute to co-ordination, precision and accurate timing of movement, this is reflected by the movements seen in someone who's cerebellum is damaged. Note it **does not** initiate movements (that's done by the motor cortex in the brain). There are some other signs seen typically in cerebellar dysfunction, as well as the ataxic gait. You may be familiar with the acronym DANISH: - D - / dysmetria dysdiadochokinesia - A - ataxia - N - nystagmus - I - intention tremor - S - scanning dysarthria - H - heel shin test dysfunction There are several complicated words/signs in this acronym! The nystagmus is distinct from vestibular induced nystagmus in that the fast phase changes depending on which direction you're looking in. An intention tremor is one that's exacerbated by movement and gets worse as the patient moves. So really, cerebellar dysfunction is relatively easy to spot! . Unlike the cerebral cortex the cerebellum gets sensory information from the same side of the body it is on, and outputs to that side. In one sided damage to the cerebellum, then the symptoms will be on the same side of the body.

Answer 101

Triad-Optic neuritis,dystharia ,intention tremor **Fatigue:** The degree of fatigue in MS is can be overwhelming and disabling - Cooling, Pacing activities, CBT, Mindfullness, Amantadine **Mood:** Depression is common in MS - CBT, SSRIs, Duloxetine **Cognition:** Cognition deteriorates as disease becomes advanced - Social support, rule out sleep issues/pain/depression **Spasticity:** This can lead to pain and discomfort - Physiotherapy, Baclofen, BoTox **Pain:** Typically neuropathic type pain - CBT, Amitriptyline, Gabapentin, Pregabalin **Neurogenic bladder issues:** Urinary frequency, urgency, nocturia. Frequent UTIs. - Fluid intake control, regimented toilet regime, Oxybutinin, BoTox injection, intermittent self-catherterisation **Constipation:** Difficulty opening bowels, or mobilising to toilet - Good diet and fluid, regular laxatives, bowel care, assisted evacuation, good hygiene Other symptoms to be aware of: - **Lhermitte's symptom: '**Electric shock' felt down back of spine on neck flexion - **Urthoff phenomenon:** Symptoms worsening in the heat e.g. hot bath

Answer 102

Transverse myelitis =leg weakness, sensory changes, bladder/bowel disturbance An area across (transverse) a section of spinal cord (myel-) that is inflammed (-itis) - May affect motor/sensory fibers or both. The types of fibres affected will produce the symptoms experienced by the patient. - May present as sensory changes (numbness, tingling) and/or motor changes (loss of power) below the level of the lesion. There is often a sensory level on examination. Signs are CNS not PNS. - Bladder, bowel and sexual function can also be involved. - The patient may feel a tight band-like sensation at the level of the lesion

Answer 103

Brainstem = dizziness, vertigo, double vision Inflammation to the brainstem or cerebellum. Many of the facial nerves have their origin in the brainstem. The head and neck sensation and power can be affected by inflammation in this area. This is rarer as a presentation of MS. - Vertigo and "room-spin" dizziness - Painless double vision as nerves controlling eye muscles are affected - Facial numbness - Dysarthria/Dysphagia The brainstem co-ordinates the cranial nerves that control eye movement, to keep the eyes moving together smoothly. If it becomes inflamed, it can't do it's job properly and the eye movements become disjointed - leading to double vision for the patient as the brain tries to make sense of these disjointed images! On **ABduction** of an eye (lateral rectus), we need to rapidly co-ordinate **ADDuction** of the other eye (medial rectus). To allow this to occur fast enough, a tract called the **medial longitudinal fasciculus** crosses over to the contralateral side of the brain stem between the nucleus of the third and sixth cranial nerve. This tract is highly **myelinated** and often affected by MS. When the **medial longitudinal fasciculus** is affected, there is a delay in **ADDuction** of the ipsilateral (same side as affected) eye when the contralateral eye **ABducts**. The term for this is **internuclear** (between cranial nerve nuclei in the brainstem) **ophthalmoplegia** (eye movement paralysis).

Answer 104

**Multiple** Sclerosis must be **Multiple** Episodes of demyelination and damage. These attacks must be disseminated in time and space. i.e. there must be attacks affecting **different areas**, at **different times**. Proof of this dissemination may be made clinically or via evidence on MRI scans. Remember, an attack gradually worsens over a few days-weeks and must last at least 24hours. The most common types of presentation are: - **Optic neuritis** - **Transverse myelitis** - **Brainstem****MRI** The 1st line investigation should be an MRI brain and spine to look for evidence of current and old inflammatory plaques. The 'classical' plaques seen in MS are peri-ventricular. These appear on the T2 MRI images as white plaques very close to the ventricles. You can also see plaques in the cerebellum, brainstem or spinal cord. Plaques in different areas can show us evidence of **dissemination in space.** Adding gadolinium contrast to the MRI scan help us see active inflammation vs old inflammation. Active inflammation enhances with gadolinium contrast, old scarring doesn't. This can show us evidence of **dissemination in time.** **Oligoclonal bands:** These are evidence of inflammation and immunoglobulin synthesis. If they are found **only**in the cerebrospinal fluid and **not** in the blood then this suggests inflammation **confined** to the central nervous system not the rest of the body. CSF oligoclonal bands are found in MS, but also in other CNS inflammatory conditions such as encephalitis, sarcoidosis, lupus etc. This test is **supportive** of an MS diagnosis ( if in keeping with a matching clinical history) but is **not specific.** The presence of oligoclonal bands in suspected MS suggests longer-term inflammation so is sometimes used as evidence supportive of **dissemination in time.** **Rule out other differential diagnosis:** If the presentation is atypical, or another cause is suspected, then tests may be performed to look for this. These may include a general bloods screen, specific autoantibodies, infection screens. These will likely be guided by an experienced neurologist based on the patient's clinical presentation.

Answer 105

The aim of treatment for a MS relapse is to speed up recovery time. Treating an MS relapse does not impact on future disability or reduced risk of future relapses. We treat relapses that cause symptoms that impact on a patient's ability to function and perform their activities of daily living. An MS relapse is treated with high dose steroids - to suppress the immune system and inflammation. This is why ruling out an infection first is so important, you don't want to suppress the immune system of someone trying to fight off an infection! MS relapses are treated with high dose IV or oral prednisolone for a few days. DMTs aim to influence the progression of the disease. They do not cure the underlying disease itself. The aim is to: - Reduced the frequency of relapses - Reduce the progression of neurodisability DMTs are given **early,** when the disease is in the **relapsing-remitting** phase. The decision about when and what disease modifying treatment to start is not easy. There are different options available. This will usually be a shared decision between a specialist consultant and the patient. You don't need to memorise all of the medications available, the guidelines are changing frequently as the research progresses. It is enough to know that different options are available, and that these are a balancing act between efficacy and safety. DMTs suppress the immune system. The stronger the DMT is, the more effective it is at reducing relapses. However, the risk of infections goes up. The condition that gets neurologists most worried is PML.

Answer 106

Optic neuritis is an inflammation of the optic nerve (cranial nerve III), reducing it's ability to carry messages. This leads to a reduction in vision, particularly colour (especially red!) vision. Movement of the eye is often painful as the inflammed and swollen nerve moves. Jenny demonstrates an example of optic neuritis: painful, blurred vision unilaterally, which has gradually developed over several days. Optic Neuritis is a common presentation of multiple sclerosis, but there are other causes. Optic neuritis = blurred vision, painful eye movements Inflammation and de-myelination of the optic nerve - Reduced visual acuity, particularly colour vision - Pain on eye movement - Relative afferent pupillary defect (RAPD) may be present

Answer 107

The first step of assessment for MS relapse should always be to **rule out infection** Infection or fevers can lead to a temporary worsening of existing MS symptoms, as opposed to a new relapse with a new episode of inflammatory de-myelination. The work-up for a possible MS relapse should always include looking for any signs of infection, particularly a UTI: - Thorough history and examination - Observations - Urine dipstick +/- culture - CXray if any respiratory symptoms/cough - Standard blood tests: FBC, U&Es, CRP As well as infection, stress/heat/over exertion can also lead to a symptom deterioration. It is important to rule these factors out first, before jumping in to starting treatement. An MRI can be useful to show evidence of a relapse if there is clinical uncertainty. A **new** lesion, which **enhances** with gadolinium contrast (showing active inflammation) is suggestive of an MS relapse. MRI is not always needed if clinical certainty is high.

Answer 108

Full Blood Count Urea and Electrolytes Thyroid Function Tests HbA1c B12/folate It is tempting to order a barrage of tests for 'the fatigued' patient, but often (especially in primary care) investigations need to be more targeted and specific. This would be a good starting point, but this list is not 100% definitive. You might also think about a ferritin (more important in weight loss, change of bowel habit, any bleeding symptoms), Liver Function Tests (important in any GI, alcohol or bleeding issues), Bone panel (calcium, magnesium, phosphate) amongst others.

Answer 109

**B12 deficiency** A B12 deficiency can cause several different neurological symptoms. B12 is found in animal products and fortified cereals. People with poor intake of B12 (strict vegans without supplementation, poor nutritional diets) and those who cannot absorb B12 (lack of intrinsic factor due to pernicious anaemia, post-gastrectomy, Crohn's disease at the terminal ileum etc.) are at risk of B12 deficiency. Body stores of B12 last for 2-4 years so it takes a long time to develop neurological symptoms from a B12 deficiency. **SACD** B12 deficiency can cause a peripheral neuropathy, affecting the distal limbs in a length-dependent pattern. B12 deficiency can also cause a condition called 'Sub-Acute Combined Degeneration of the Cord' (SACD). This is a de-myelination of the fibres of the dorsal and lateral areas of the spinal cord. Dorsal column: Vibration and Proprioception sense Lateral corticospinal tract: A descending motor pathway This means that SACD presents with a mix of Sensory and UMN motor signs. A patient may experience reduced sensation, reduced vibration/proprioception and ataxia as well as spastic loss of power and upgoing plantars (positive Babinski sign).

Answer 110

B12 deficiency,. Folate deficiency Hypothyroidism: Alcohol: Alcohol is another common cause of a raised MCV, Acute illness/bone marrow stress: sepsis/trauma/bone marrow dysplasia conditions

Answer 111

Supporting this theory, 2/3 of GBS patients have an upper respiratory tract infection or gastroenteritis (viral or bacterial) in the 6 weeks before disease onset 2. The most commonly identified trigger is a Camplyobacter jejuni infection, hence this patient's preceding diarrhoea. Furthermore, antibodies to specific gangliosides (compounds found mostly in the nervous system) are strongly associated with different variants of GBS.

Answer 112

It is also worth briefly noting at this point that there are multiple other variants of GBS, which you do not need to know in detail. These include variants that cause only sensory symptoms, axonal injury instead of demyelination, and a variant called Miller-Fischer syndrome that causes eye weakness (ophthalmoplegia). Classically, patients with AIDP present with mild paraesthesia of the lower limbs. This is followed by progressive weakness that starts in the lower limbs and progresses to the upper limbs. Patients develop a flaccid paresis with areflexia. This is due to demyelination of lower motor neurons. Despite the paraesthesia, patients often have no sensory deficit on examination. There is usually back or leg pain due to nerve root inflammation. patient has wasting as a long-term consequence of GBS. This occurs in a minority of patients. You would not see wasting in your patient acutely. Autonomic symptoms can occur due to inflammation of autonomic ganglia. However, bladder/bowel symptoms tend to occur later on, if at all. Therefore, early symptoms would make you more suspicious of spinal cord lesions / cauda equina. Other autonomic symptoms include sudden changes in BP and HR, as well as arrhythmias (rarely). The course of the disorder is variable but the majority of patients have reached the worst point of their illness by 2 weeks. This is followed by a plateau phase, which is very variable. The majority of patients make a dramatic recovery after their plateau and at least 28 days after onset. Most patients have a return to daily function but are left with some form of residual deficit e.g. fatigue, weakness and pain. 20% of patients are still unable to walk at 6 months and there is a mortality of 3-10%. 3 Mortality is largely due to the significant risk of respiratory muscle involvement (40%) and neuromuscular respiratory failure (25%) 4. Therefore patients need to have regular forced vital capacity (FVC) assessments. This is the pulmonary function test in which the patient exhales their maximum volume of air, following a maximal inspiration. Poor / worsening FVC has been found to be the most useful prognostic indicator of the need for ventilation (covered in the treatment section). Observations that might usually be helpful for indicating respiratory failure, such as dropping O2 saturation, occur much later in GBS.

Answer 113

Routine blood tests for patients with GBS are often normal but they may have mildy raised CK and abnormal LFTs. It is useful to check for inflammatory markers, which should not be raised (GBS occurs after the infection), and biochemical markers that can affect nerve function (e.g. hypocalcaemia). Anti-ganglioside antibodies can be tested for specific GBS variants if the diagnosis is unclear. Lumbar puncture in these patients is useful and should show 'albuminocytologic dissociation'. This means that there is elevated protein in the cerebrospinal fluid (CSF) but little or no cells (cytologic). In other words, there aren't any cells in the CSF to account for the high protein. It is not fully understood why this is the case. You do not need to memorise these numbers but the cell count is usually less than 50 and the protein is greater than 0.55 g/L. The other useful tests are nerve conduction studies (NCS) / electromyography (EMG). These tests measure the response of nerves and muscles respectively to electrical stimulus. This essentially allows us to localise the pathology to the peripheral nerves and note acquired patchy demyelination. It should be noted that these abnormal signs on lumbar puncture and NCS/EMG are present in more patients 7 days after presentation than when tested earlier. It is therefore possible to do these investigations too early and be falsely reassured by results. You would discuss these decisions with a neurologist.

Answer 114

The main treatment for GBS is either plasma exchange (PLEX) or intravenous immunoglobulin. Both of these treatments have similar efficacy in GBS and are not beneficial in combination. Plasma exchange (AKA plasmapheresis), is a therapy by which blood is extracted from the patient from a large vein (via a line) and the plasma is separated from other blood contents. The patient's autoantibodies are contained within the plasma as so this part of of the blood is discarded. The patient's remaining blood products (RBCs, WBCs and platelets) are mixed with donor plasma or an albumin/saline solution and returned to the patient. Intravenous immunoglobulin (IVIg) is a therapy by which high dose donor immunoglobulin is given intravenously to the affected patient. Exactly why this works is not known but IVIg appears to neutralise the effect the patient's autoantibodies and modulate the immune response. 7 Both of these treatments are effective in improving recovery time, admission time, time to walk again unaided and reducing the likelihood of the patient requiring ventilation. Steroids have not been found to be useful for treating GBS. is also important to consider supportive management of the patient. We have mentioned that there can be autonomic dysfunction in these patients. Changes to heart rate and blood pressure can be treated, if necessary, with short acting medication as we know that these changes are labile. Patients may need catheterisation if they develop urinary retention. They are highly likely to develop constipation due to immobilisaton, even without autonomic dysfunction. Therefore laxatives are often prescribed. Immobilisation also increases the risk of venous thromboembolism and these patients usually require prophylactic dose anticoagulation until their mobility improves. Some patients also need nutritional support by tube feeding. Patients with an FVC of less than 20ml/Kg are associated with progression to respiratory failure and intensive care admission should be considered. This is for invasive / mechanical ventilation to provide the alveoli with new air to undergo gaseous exchange. Giving high concentration oxygen alone is less helpful here because this in not reaching the alveoli.

Answer 115

Parkinsonism as a description of a collection of signs: - Bradykinesia (slowness of movement and decrement on rapid, alternating movements) **+ at least one of:** - Rigidity (muscle stiffness) - Postural instability - Tremor Idiopathic Parkinson's Disease is the most common cause of Parkinsonism, but there are other causes. These are explored further in the lecture on Parkinson's disease. Drug-induced Parkinsonism (think anti-pyschotics), Vascular and the 'Parkinsonian plus' conditions are possibilities. There are a few **key features** in the history that could help us differentiate between the Parkinsonian Plus conditions. **Progressive Supranuclear Palsy:** - Early **backwards** falls - **Gaze palsy**, particularly on looking vertically - Axial (body) rigidity - May have more frontal lobe signs **Multiple Systems Atrophy:** - Early **severe autonomic** dysfunction - Postural hypotension, may lead to faints - Urinary symptoms, may lead to incontinence - Signs may be more Parkinsonian, or more cerebellar **Corticobasal Degeneration:** - Very rare - Asymmetrical signs, **one limb most affected** - Cortical sensory loss - 'alien limb syndrome', dyspraxia, shape recognition **Lewy Body Dementia:** - Dementia **precedes** the Parkinsonian features - Fluctuates **Visual hallucinations** - often children/animals In the past we used to think of PD as a condition of "shaking and slowness". James Parkinson's original descriptions were entitled "the shaking palsy". As we have better understood the condition we have to learned to see it as a much more 'multi-system' illness. We tend to split the symptoms into motor (relates to muscles and movement) and non-motor (everything else). We are starting to recognise that there are 2 main sub-types of Parkinson's Disease: - Tremor dominant - Postural Instability and Gait Disturbance (PIGD) Non-motor symptoms may become more prominent over time as the disease gradually progresses.

Answer 116

The non-motor symptoms are numerous and varied: **Balance and falls:** - Postural instability (poor balance) - Postural hypotension - Eyesight problems (dry eyes, blurred or double vision) **Bladder and bowel** - Constipation - Gastroparesis - Urinary symptoms (urgency, frequency, nocturia) - Erectile dysfunction **Speech and swallow** - Dysphagia - Excess salivation/drooling - Hypophonia (quiet voice) - Anosmia (loss of sense of smell, often pre-dates the physical symptoms) **Sleep** - Insomnia (fragmented sleep, rather than trouble falling asleep) - REM sleep disorder (Loss of usual paralysis during sleep, leading to vivid dreams and acting out their dreams e.g. punching a bed partner!) - Restless legs syndrome **Mood and cognition** - Cognitive impairment - Anxiety - Depression - Apathy (remember, this is different to depression. Initiation/planning is reduced, but the patient can still enjoy things and do not necessarily have low mood) - Visual hallucinations - Psychosis - Pain

Answer 117

. If you are unsure, discussing with your team is always your best option. Always try to give medications in their oral form if possible, 'Nil By Mouth' sometimes means small sips or tablets can be taken. Always check with the nurses and SALT team about the 'NBM' order. Do not give anything orally unless you are sure and have discussed this. If this patient is going to be NBM for a prolonged period they will need some form of nutrition so may need an NG tube for feeding. Medications can also be given via an NG tube. 2. If the oral route is unavailable then medication patches are the next best option. Rotigotine is a dopamine agonist that can be given in 24 hour patch form. Check the dose conversion using online resources (e.g. OPTIMAL calculator) and ask the ward pharmacist to assist and check your conversions. Remember, the conversion is not perfect and some patients may experience side effects with a dopamine patch. Always give their usual medication in oral form if possible. 3. Withholding medication is not a good option. Missing doses of medication leads to deterioration of symptoms and patient compromise. The swallow is likely to be worse after several days without medication. Sudden withdrawal of medication can also lead to Neuroleptic Malignant Syndrome. 4. Levodopa does not come in an IV form, this is an actively dangerous and unsafe option so is ranked as the worst choice. If you are unsure about PD medications the best option is to refer the patient and ask for help! Informing the SALT team and pharmacist is a good place to start. Remember, the best option is always their usual medication, in the usual form at the usual times. If that's unavailable, then consider nasogastric tube placement or a transdermal patch. Never omit Parkinson's medications!

Answer 118

In younger patients with few medical co-morbidities it is often a good idea to start with a dopamine agonist or MAO-B inhibitor. This allows us to delay starting levodopa and avoid early problems with prolonged levodopa use. Older patients with more co-morbidities +/- frailty will often be less able to tolerate the side effects of dopamine agonists. They will tend to be started on Levodopa as a first line agent and low doses of other medications can be added later if tolerated to keep symptoms under control. Levodopa Co-beneldopa (Madopar), Co-carledopa (Sinemet) Dopamine agonists Pramipexole, Ropinirole, Rotigotine, Apomorphine MAO-B inhibitors Rasagiline, Selegiline COMT inhibitors Entacapone Amantidine- Dyskinesia Levodopa often works very effectively for the first 5-7 years of use, sometimes referred to as the 'Honeymoon' period'. After this time some patients will start to experience motor fluctuations where the dose of levodopa doesn't offer consistent control of their symptoms throughout the day. This causes three main issues: - **Wriggling:** Peak-dose dyskinesia (increased movement e.g. twitching, writhing, jerking, twisting) as levodopa reaches it's maximum concentration in the blood 1-2 hours after the dose is taken - **Wearing off:** "Wearing off" effect where Parkinsonian symptoms (rigidity, bradykinesia, tremor etc) start to re-occur before the next dose is due, when levodopa is at it's minimum concentration in the blood - **Waiting:** "Delayed on" effect where it takes an increased time for levodopa to start having an effect after the tablet is taken. Over time the number of doses may have to be gradually increased to keep giving the same benefit to the patient. The risk of developing these medication issues increases with prolonged and high dose therapy. **Dopamine Agonists** Dopamine agonists are useful medication as an early alternative to Levodopa or in combination, to allow lower dosages to be used. As with all medications, consideration must be given to their unwanted side effects. - Postural hypotension - Hallucinations - Poor sleep and daytime solomnence - Impulse control disorders: Patient's can start to experience issues with gambling, excess shopping, hypersexuality or binge eating It is important to warn patients to watch out for these side effects when starting any new medications or changing doses!

Answer 119

Some patients think that Deep Brain Stimulation (DBS) offers a 'miracle cure' for their condition and will ask their doctor about having one inserted. Whilst DBS can offer huge benefits to symptom control for some patients, sadly, it is not appropriate for everyone. The main points to be aware of are: - Works mostly on motor symptoms (eg. tremor) rather than non-motor. - Symptoms need to be dopamine responsive (i.e. a proven benefit on dopaminergic medications) to know that DBS could help. - DBS can make some things worse: Balance, eye lid opening, speech, swallow and cognition can be worsened by DBS. Anyone with pre-existing issues in these areas would not be appropriate for DBS. Going for DBS is a significant undertaking for patients and it must be a shared decision between patient and clinician after consideration of the risks and benefits. Have a look at this video to see what can be possible when things go well

Answer 120

Lateral medullary syndrome, also known as Wallenberg's syndrome, occurs following occlusion of the posterior inferior cerebellar artery. Cerebellar features ataxia nystagmus Brainstem features ipsilateral: dysphagia, facial numbness, cranial nerve palsy e.g. Horner's contralateral: limb sensory loss Weber's syndrome (branches of the posterior cerebral artery that supply the midbrain) Ipsilateral CN III palsy Contralateral weakness of upper and lower extremity Other Posterior Stroke Syndromes Basilar artery occlusion is more likely to present with locked in syndrome (quadriparesis with preserved consciousness and ocular movements), loss of consciousness, or sudden death. Anterior inferior cerebellar artery results in lateral pontine syndrome, a condition similar to the lateral medullary syndrome but with additional involvement of pontine cranial nerve nuclei.

Answer 121

Motor neuron disease can be classified clinically and pathological according to the distribution of motor neuron involvement. As present our characterisation is limited to distinguishing sporadic from familial disease, and division into four clinical groups. The most common variant, known as amyotrophic lateral sclerosis, affects both upper and lower motor neurons and therefore manifests as a mixed clinical picture of upper and lower motor neuron signs. The four clinical groups are: Spinal ALS (the classic MND syndrome) Bulbar ALS (with early tongue and bulbar involvement) Progressive muscular atrophy (with only lower motor neuron features) Primary lateral sclerosis (with only upper motor neuron features).

Answer 122

Clinical features Early bulbar and respiratory muscle involvement, and older age at onset carries the poorest prognosis. In contrast, more prominent lower motor neuron features is associated with more protracted survival. Classically, there is a combination of upper motor neuron and lower motor neuron signs. Upper motor neuron signs include spasticity, hyperreflexia and upgoing plantars (though they are often down going in MND). Lower motor neuron signs include fasciculations, and later atrophy. Generally, the eye and sphincter muscles are spared until late in the disease course and sensory disturbance is NOT seen (and should prompt consideration of an alternative diagnosis). The diagnosis of motor neuron disease is clinical, but nerve conduction studies will show normal motor conduction and can help exclude a neuropathy. Electromyography shows a reduced number of action potentials with increased amplitude. MRI is usually performed to exclude the differential diagnosis of cervical cord compression and myelopathy *vague sensory symptoms may occur early in the disease (e.g. limb pain) but 'never' sensory signs Treatment of motor neuron disease Currently there is only one disease modifying treatment available for motor neuron disease, and its results are modest at best: Riluzole (an antiglutamatergic drug which dampens motor nerve firing) has been shown to prolong life by 3 months. Non-invasive ventilation can also prolong survival in patients with type 2 respiratory failure. Treatment focus is therefore supportive and best coordinated via and MDT approach. Pain relief is important, with simple analgesia as well as the treatment of spasticity and contractures with baclofen and botox injections. Drooling may be helped by anticholinergics (including the TCAs), and eventually supportive feeding via an NG or PEG may be indicated as bulbar disease progresses. Early discussion of advanced care planning should also be initiated to minimise distress and complications as disease progresses.

Answer 123

Myasthenia gravis is an autoimmune disorder resulting in insufficient functioning acetylcholine receptors. Antibodies to acetylcholine receptors are seen in 85-90% of cases*. Myasthenia is more common in women (2:1) The key feature is muscle fatigability - muscles become progressively weaker during periods of activity and slowly improve after periods of rest: extraocular muscle weakness: diplopia proximal muscle weakness: face, neck, limb girdle ptosis dysphagia Associations thymomas in 15% autoimmune disorders: pernicious anaemia, autoimmune thyroid disorders, rheumatoid, SLE thymic hyperplasia in 50-70%

Answer 124

Investigations single fibre electromyography: high sensitivity (92-100%) CT thorax to exclude thymoma CK normal autoantibodies: around 85-90% of patients have antibodies to acetylcholine receptors. In the remaining patients, about about 40% are positive for anti-muscle-specific tyrosine kinase antibodies Tensilon test: IV edrophonium reduces muscle weakness temporarily - not commonly used any more due to the risk of cardiac arrhythmia Management long-acting acetylcholinesterase inhibitors pyridostigmine is first-line immunosuppression: prednisolone initially azathioprine, cyclosporine, mycophenolate mofetil may also be used thymectomy Management of myasthenic crisis plasmapheresis intravenous immunoglobulins

Answer 125

Lambert-Eaton myasthenic syndrome is seen in association with small cell lung cancer and to a lesser extent breast and ovarian cancer. It may also occur independently as an autoimmune disorder. Lambert-Eaton myasthenic syndrome is caused by an antibody directed against presynaptic voltage-gated calcium channel in the peripheral nervous system. Features repeated muscle contractions lead to increased muscle strength (in contrast to myasthenia gravis) in reality, this is seen in only 50% of patients and following prolonged muscle use muscle strength will eventually decrease limb-girdle weakness (affects lower limbs first) hyporeflexia autonomic symptoms: dry mouth, impotence, difficulty micturating ophthalmoplegia and ptosis not commonly a feature (unlike in myasthenia gravis) EMG incremental response to repetitive electrical stimulation Management treatment of underlying cancer immunosuppression, for example with prednisolone and/or azathioprine 3,4-diaminopyridine is currently being trialled works by blocking potassium channel efflux in the nerve terminal so that the action potential duration is increased. Calcium channels can then be open for a longer time and allow greater acetylcholine release to the stimulate muscle at the end plate intravenous immunoglobulin therapy and plasma exchange may be beneficial

Answer 126

exposure related-drug Induced(chemotherapy,Methotrexate,Amiodarone) Occupational(fumes, organic,Inorganic fumes) Hypersensitivity Autoimmune relayed-RA,SLE,Scleroderma,Polymyositis Idiopathic-IPF,Acute interstitial pneumonia Examples Pulmonary fibrosis,Hypersenstivity Pneumonitis,Sarcoidosis,Pneumoconiosis,

Answer 127

History-Autoimmune disease, job,occupation,pets,drugs(methotrexate, Nitrofurantoin,Amiradone) Common features of IDL include: - Cough - dry and persistent - Breathlessness - secondary to poor lung compliance - Cyanosis - Crackles - typically bilateral and basal, typically fine crackles often described as "velcro-like" - Clubbing - common in idiopathic pulmonary fibrosis, pathophysiology not fully understood, also seen in other conditions - Exertional hypoxemia - due to maldistribution of ventilation and perfusion An examination of the cardiac system is also helpful, looking for signs of left and right heart failure. Other non thoracic signs may also be present if the ILD is a result of a systemic illness eg. rash in sarcoidosis.

Answer 128

Idiopathic Pulmonary Fibrosis (IPF) is the most common of the idiopathic pneumonias. There is no evidence of an alternative cause eg. drugs, environmental exposure or a system condition. It is chronic and progressive, and can be more common in males. Clinical Features: - Insidious onset of shortness of breath and cough - Exertional dyspnoea - Malaise - Weight loss - Arthralgia - Fever Often patients will be diagnosed as recurrent chest infections before the diagnosis of IFP is considered. Important things to look for in the examination are Fine end-inspiratory crackles are oft described as velcro crackles A thorough examination of the cardiovascular system is also recommended

Answer 129

Investigations for IPF should include - ABG - Autoantibodies and serum ACE (to rule out other known causes) - CXR - Lung Function Tests - CT/High Resolution CT Spirometry showing Obstructive and Restrictive Lung Disease ([Source:By CNX OpenStax [CC BY 4.0) Lung function tests in IPF with show a restrictive pattern: - Reduced FEV1 (<80% of the predicted normal) - Reduced FVC (<80% of the predicted normal) - FEV1/FVC ratio normal (>0.7) In pulmonary fibrosis-total lung capacity reduced This ABG shows Type one respiratory failure which is typical of IPF. CXR findings: Decreased lung volume, bilateral lower zone reticulonodular shadows and honeycomb lung in advanced disease CT findings: Diffuse reticular infiltration of both lungs associated with honeycombing Treatment Approach to management in IPF: **Conservative** - Best supportive care - Oxygen - Pulmonary Rehab - Palliative care when appropriate **Medical** - Perfenidone - anti-fibrotic properties, can stabilize lung function - Nintedanib **Surgical** - Lung transplant

Answer 130

``` Post CABG assessment Assessment of Aorta Assessment of pulmonary vessels Congenital anomalies of the heart Assessment of prosthetic valves Assessment of cardiac masses Assessment of pericardium ```

Answer 131

Includes Cardiac Calcium scoring (without contrast) Cardiac Angiography (with Contrast) To begin with a cardiac calcium scoring is done without contrast. Depending on the score, further need for angiography is decided. E.g.. If the score is 0 or >400: No need for further Angiography. If intermediate, then proceed with angiography. Calcium scoring It is done without a contrast. It measures whether calcified atherosclerotic plaque is present in the vessels or not. Based on the principle that Obstructive atherosclerotic plaques are calcified. Calcium is not present in the walls of a normal coronary artery. It is a semi-automated measure. We have to look at the coronary arteries, one by one and click on the visible hyperdensity(calcium), and a automated score is obtained . The scores of all the vessels are added up to get a final score.

Answer 132

Advantages ``` Non invasive Fast Calcium scoring 3D reconstruction Can see beyond the lumen(atheroma imaging) ``` Disadvantages Contrast requirement(adequate renal function) Limited spatial resolution Radiation Requires slow heart rate(preferably<60BPM) No hemodynamic information Movement artefacts Limitation if high amount of calcium is present in the vessels. Obese and Unco-operative patient Stents

Answer 133

Indication Cardiogenic shock HF stage 3 /4 progressive symptoms with maximal therapy Severe symptomatic hypertrophic and restrictive cardiomyopathy Cardiac masses non metasisi hypo plastic left heart syndrome and congenital heart diseases Life threatening arrhythmia Medically refractory angina Contraindications ``` Severe Pulmonary HTN >6 Wood units not responsive to vasodilators Active infection Uncontrolled Malignancy Irreversible end-organ disease Hepatic, Renal, Pulmonary Pulmonary Infarction Age >60 years Diabetes mellitus with end-organ damage Severe Cerebral and Peripheral Vascular Disease ```

Answer 134

All recipients are given Cyclosporine f or immunosuppression Induction may be difficult due to failing heart Must keep heart rate high to maintain higher C.O. with patients with low stroke volume Surgical Techniques; Orthotopic Heart Transplant- (Most Common) Native heart completely removed - and replaced Contraindicted in PTN Biatrial anastomosis-shorter schema time, size mismatch,arrythmias Bicaval anastomosis-narrowing SCV,IVC ,less arrhythmia Heterotopic Heart Transplant- Donor heart placed in parallel with native – two heartsin REVERSAL hf Pros- Native heart gives the donor heart a helpful kick Offers some protection against rejection of the donor heart Cons- Decreased survival rate Still have to medically manage a failing native heart Native heart is a site of thrombus

Answer 135

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Answer 136

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Answer 137

Primary Pathology predominantly involves the heart Examples: Dilated cardiomyopathy Hypertrophic cardiomyopathy Restrictive cardiomyopathy Arrhythmogenic right ventricular cardiomyopathy Obliterative cardiomyopathy ``` Secondary Autoimmune-Dermatomyositis Rheumatoid arthritis Scleroderma Infection-Chagas disease HIV Hepatitis C Rickettsia Viral (adenovirus, Coxsackie, Epstein-Barr, parvovirus) Endocrine-Acromegaly Diabetes mellitus Hyperthyroidism Hypothyroidism Hyperparathyroidism Obesity Toxins-Alcohol Anabolic steroids Chloroquine Heavy metals (arsenic, cobalt, lead) Haemochromatosis Stimulants (cocaine) ``` others Amyloidosis Gaucher disease Hunter Syndrome Kwashiorkor Niacin deficiency Glycogen storage disorders Neurofibromatosis Muscular dystrophy (Becker’s, Duchenne, myotonic)

Answer 138

Autosomal dominant Other causes-Cox sackie B,DoxirubinAlchol,Beri beri Clinical-Fatique,dyspnea,PE,RVF,AF Sign-increase pulse, bp,JVP,DISPLACED APEX,s3 gallop, mitral tricuspid regurgitation,jaundice,hepatomegaly ``` Prevalence 1:2500 May present with: Heart failure Cardiac arrythmia Conduction defects Thromboembolism Sudden death Family history should be obtained ``` ``` inx BNP ECG low sodium-poor prognosis Cardiac MRI Coronary angiography To exclude coronary artery disease ``` Endomuocaridal biopsy Acute dilated cardiomyopathy + refractory heart failure symptoms Dilated cardiomyopathy in presence of systemic diseases SLE, Polymyositis, Sarcoidosis Rapidly progressive ventricular dysfunction In unexplained, recent onset cardiomyopathy New onset cardiomyopathy + recurrent VT/ high grade heart block Heart failure in the setting of fever, rash and peripheral eosinophilia Management Manage symptoms of cardiac failure-ACE1,diuretics,beta blockers Implantable Cardioverter Defibrillator (ICD),LVAD Cardiac transplant

Answer 139

Left ventricular hypertrophy In absence of causative haemodynamic factors: Hypertension, aortic valve diseases, systemic diseases, storage diseases Prevalence 1:500-1:1000 Men : women = 2:1 African-Americans : Caucasians = 2:1 Commonly reported in North America, West Europe, Asia Autosomal dominant with incomplete penetrance Mutation in genes encoding for sarcomere proteins Myosin, actin, troponin, tropomyosin Genetic basis does not directly correlate with prognostic risk stratification Classified into obstructive and non obstructive

Answer 140

Left Ventricular Outflow Obstruction (Asymmetrical hypertrophy of interventricular septum (ASH) Systolic anterior motion (SAM) of mitral valve Leaflets of mitral valve move towards enlarged septum during systole Mitral valve leaflets obstructs blood flow from ventricles to aorta Narrowing of outflow tract Major determinant for heart failure symptoms, and death ) Elevated intraventricular pressure Prolonged ventricular relaxation Leads to diastolic dysfunction Increased myocardial wall stress Increased bodily oxygen demand Decreased cardiac output Mitral regurgitation (Result from systolic anterior motion of mitral valve Severity directly proportional to outflow obstruction Patients complain of dyspnoea and orthopnoea ) Diastolic dysfunction ``` (Impaired ventricular relaxation High systolic contraction load Contraction/ relaxation of ventricles not uniform Exertional dyspnoea symptoms Abnormal diastolic filling Increased pulmonary venous pressure ) ``` Myocardial ischemia (Often occurs without atherosclerotic coronary artery disease Postulated mechanism: Abnormally small +/- partially obliterated intramural coronary arteries Due to hypertrophy Inadequate number of capillaries for the degree of mass )

Answer 141

``` Symptoms* Chest pain Dyspnoea Syncope with exertion Pulmonary oedema Cardiac arrhythmias e.g. atrial fibrillation Sudden death ``` Signs- Palpation of pulses Double apical pulsation Forceful atrial contraction Jerky carotid pulse Short upstroke, prolonged systolic ejection Jugular venous pulse Prominent a wave: decreased ventricular compliance ``` Signs- Auscultation Fourth heart sound (S4) Cardiac hypertrophy Ejection systolic murmur Along left lower sternal border Intensity increase with decreased preload (Valsalva manoeuvre), vice versa (during squatting) Mitral regurgitation Secondary to SAM (systolic anterior motion) ``` ``` INX- ECG(Left ventricular hypertrophy Presence of septal Q waves) Echocardiography (Used for: Diagnosis Haemodynamic assessment Clinical risk stratification Interventional management ``` ``` Findings: Left ventricular hypertrophy (LVH) Asymmetrical septal hypertrophy (ASH) Systolic Anterior Motion (SAM) )LVH ≥15mm (Asymmetric > Symmetric) Absence of other cardiovascular/ systemic disease associated with LVH/myocardial wall thickening ``` Cardiac Magnetic Resonance (CMR) Indicated when ECHO views are limited Due to unusual distribution of hypertrophy Detect milder magnitudes of hypertrophy Demonstrates myocardial scarring Differentiate hypertrophic cardiomyopathy from other LVH Gadolinium enhanced imaging detect myocardial scarring in ~2/3 of patients with hypertrophic obstructive cardiomyopathy Cardiac Catheterisation Not typically necessary in HCM Hyperdynamic systole function results in almost complete obliteration of left ventricular cavity Management Aims: Treat symptoms Prevent sudden death ``` Options: Medications Dual-chamber pacing Implantable Cardioverter Defibrillator (ICD) Surgical septal myomectomy Alcohol septal ablation ``` Beta-blockers During chest pain Increase ventricular diastolic filling/ relaxation Decrease myocardial oxygen consumption Not been shown to reduce incidence of sudden cardiac death Verapamil During chest pain Augments ventricular diastolic filling/ relaxation

Answer 142

``` Predominantly affects right ventricle Population prevalence 1 : 5000 Autosomal dominant inheritance Fatty/ fibro-fatty replacement of myocytes Leads to ventricular dilation ``` ``` Clinical Most patients asymptomatic Symptoms (if present): Ventricular arrhythmia Syncope Right heart failure Increased risk of sudden death ```

Answer 143

inx ``` ECG Usually normal May show T-wave inversion in right ventricular leads (V1, V2)/ features of RBBB 24-hours Holter monitoring Non-sustained ventricular tachycardia Echocardiography Right ventricular dilation + aneurysm formation (in advanced cases) Cardiac Magnetic Resonance Fibrofatty infiltration ``` ``` Treatment Amiodarone Symptomatic arrhythmias Beta blockers Non-life threatening arrhythmias Implantable Cardioverter Defibrillator (ICD) Life threatening arrythmias Cardiac transplant Intractable arrhythmia Cardiac failure ```

Answer 144

Prominent trabeculations, deep recesses in apex of left ventricle Thin compact epicardium, thickened endocardium Increased risk of thrombosis, heart failure, ventricular tachycardia and sudden death Risk of offspring inheriting disease

Answer 145

1/3 of dilated cardiomyopathy cases in the Western world Risk increases with alcohol consumption >10 years Advice early alcohol abstinence Chronic, insidious onset Result of Direct toxin from alcohol Thiamine deficiency ``` Clinical Presentation: Dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoea Palpitation Syncope Chest pain Pleural effusion ECG findings: Atrial fibrillation/ Atrial flutter QT prolongation Poor R-wave progression Premature ventricular contraction LBBB/RBBB 1st degree atrioventricular block ```

Answer 146

Systolic heart failure (LVEF <45% / fractional shortening <30%) In the last month of pregnancy/ within 5 months of delivery Other determinable aetiology of heart failure absent Absence of any heart disease before last month of pregnancy Fractional shortening: Reduction of length of end-diastolic diameter by the end of systole Measures heart’s muscular contractility Efficiency of heart in ejecting blood impaired when diameter fails to shorten by >28%

Answer 147

Haemochromatosis: Ventricular and cardiac conduction system involvement Complications: ventricular wall thickening, dilated cardiomyopathy, restrictive cardiomyopathy Fabry disease: Glycolipid deposition in endothelium, myocardium, mitral valve Complications: hypertension, mitral regurgitation, heart failure Gaucher disease: Cerebrosides (glycosphingolipids) deposition Complications: left ventricular dysfunction, haemorrhagic pericardial effusion

Answer 148

Diastolic insufficiency Impaired ventricular filling Ventricles stiff and rigid Increased tension of ventricular filling Systolic function normal in early stages Intraventricular pressure rises precipitously with small increase in volume Causes ``` Primary restrictive cardiomyopathy Idiopathic Loeffler eosinophilic endomyocardial disease (for your interest) Secondary restrictive cardiomyopathy Amyloidosis Sarcoidosis Haemochromatosis ``` Morphology ``` Hypertrophy of myocardium Myocardium becomes firm Thickening of endocardium Both atrium dilated Due to diastolic disturbances Ventricle size slightly enlarged No dilation of cavities Ventricle walls loss elasticity ``` Under microscope -Patchy/ diffuse interstitial fibrosis/ amyloid

Answer 149

clinical Symptoms Fatigue Dyspnoea Tachypnoea ``` Examination findings Increased JVP Hepatic enlargement Ascites Oedema S4 heart sounds ``` Inx Examination findings ``` Increased JVP Hepatic enlargement Ascites Oedema S4 heart sounds Echocardiography Symmetrical myocardial thickening Impaired ventricular filling Cardiac Magnetic Resonance Myocardial fibrosis in amyloidosis Endomyocardial biopsy ``` Management No specific treatment Manage cardiac failure and embolic manifestations Cardiac transplant in selected cases Melphalan, prednisolone, colchicine may improve survival in primary amyloidosis

Answer 150

``` Rare form of restrictive cardiomyopathy Thrombosis + fibrosis + obliteration of ventricular cavities Involves endocardium of one or both ventricles Endocardium thickens Features: Mitral + tricuspid valve regurgitation Heart failure Pulmonary embolism Systemic embolism ``` Associated with: Eosinophilic leukaemia Chrug-Strauss syndrome Management: Anticoagulants + antiplatelets Manage heart failure Tricuspid and mitral valve replacement +/- decortication of endocardium