Chemotherapy is a common treatment for cancer, but it can also cause severe side effects. One such drug is 5-fluorouracil (5-FU), which is metabolically activated to 5-fluoro-2’deoxyuridine-5-monophosphate (F-dUMP) and inhibits DNA synthesis. The breakdown of 5-FU is carried out by dihydropyrimidine dehydrogenase (DPD), and a pharmacogenetic disorder can cause a deficiency of this enzyme, leading to severe toxicity and potentially fatal outcomes. Rapid administration of 5-FU can also cause reactions, but it is unlikely to be the cause of severe symptoms. Similarly, a low dose of folinic acid, which is given concurrently with 5-FU, is unlikely to cause such symptoms. Therefore, understanding the genetic susceptibility to toxicity from 5-FU due to a deficiency of the catabolising enzyme is crucial in managing the side effects of chemotherapy.

The patient’s chronic liver disease is showing signs of decompensation, likely due to Budd-Chiari syndrome which is supported by CT findings of poor visualization of the hepatic veins and hypoattenuation of the peripheral zones. The patient’s ferritin level below 1000 ng/mL suggests that their alcohol intake may be truthful, ruling out haemochromatosis as a cause. The ascitic fluid analysis does not indicate spontaneous bacterial peritonitis. While hepatocellular carcinoma is a known complication of chronic liver disease, the patient’s ultrasound does not show any features consistent with this diagnosis.

Decompensated Liver Disease: Causes, Signs, and Management

Decompensated liver disease is a condition where the liver is unable to function properly, leading to various complications. There are several causes of decompensation, including infections such as pneumonia and viral hepatitis, drugs like paracetamol and anaesthetic agents, toxins such as alcohol and Amanita phalloides mushroom, vascular disorders like Budd-Chiari syndrome and vena-occlusive disease, haemorrhage from upper gastrointestinal bleed, and constipation.

The signs of decompensated liver disease include asterixis, jaundice, hepatic encephalopathy, and constructional apraxia, which is a difficulty in drawing a clock face. To manage this condition, it is important to investigate and identify the underlying causes of decompensation. This may involve checking blood tests, reviewing the drug chart, performing a rectal examination for melaena and constipation, and conducting a septic screen.

To enhance nitrate clearance, phosphate enemas can be used to achieve a minimum of three loose stools per day. Lactulose can also be administered to enhance the binding of nitrate in the intestine. Proper management of decompensated liver disease can help prevent further complications and improve the patient’s quality of life.

Understanding Multiple Endocrine Neoplasia

Multiple endocrine neoplasia (MEN) is an autosomal dominant disorder that affects the endocrine system. There are three main types of MEN, each with its own set of associated features. MEN type I is characterized by the 3 P’s: parathyroid hyperplasia leading to hyperparathyroidism, pituitary tumors, and pancreatic tumors such as insulinomas and gastrinomas. MEN type IIa is associated with the 2 P’s: parathyroid hyperplasia leading to hyperparathyroidism and phaeochromocytoma, as well as medullary thyroid cancer. MEN type IIb is characterized by phaeochromocytoma, medullary thyroid cancer, and a marfanoid body habitus.

The most common presentation of MEN is hypercalcaemia, which is often seen in MEN type I due to parathyroid hyperplasia. MEN type IIa and IIb are both associated with medullary thyroid cancer, which is caused by mutations in the RET oncogene. MEN type I is caused by mutations in the MEN1 gene. Understanding the different types of MEN and their associated features is important for early diagnosis and management of this rare but potentially serious condition.

In 2011, the National Institute for Clinical Excellence updated its guideline for managing hypertension, emphasizing the use of ambulatory blood pressure monitoring (ABPM) as the first line of diagnosis for those with elevated clinic readings. ABPM involves taking two measurements per hour during waking hours and using the average of at least 14 measurements to confirm hypertension.

Secondary causes of hypertension should be investigated in patients under 40 without traditional risk factors, those with other symptoms, and those with resistant hypertension. Hyperaldosteronism is the most common cause, and a trial of spironolactone may be used for both diagnosis and treatment.

Drug treatment for essential hypertension follows a stepwise approach, with ACE inhibitors recommended for those under 55 and calcium channel blockers for those over 55 or of black African or Caribbean origin. Combination therapy with ACE inhibitors and calcium channel blockers is recommended in step 2, followed by the addition of a thiazide-like diuretic in step 3. Further diuretics, beta-blockers, or alpha blockers may be considered in step 4, with expert advice sought. For more detailed information, see the provided link.

NICE released updated guidelines in 2019 for the management of hypertension, building on previous guidelines from 2011. These guidelines recommend classifying hypertension into stages and using ambulatory blood pressure monitoring (ABPM) and home blood pressure monitoring (HBPM) to confirm the diagnosis of hypertension. This is because some patients experience white coat hypertension, where their blood pressure rises in a clinical setting, leading to potential overdiagnosis of hypertension. ABPM and HBPM provide a more accurate assessment of a patient’s overall blood pressure and can help prevent overdiagnosis.

To diagnose hypertension, NICE recommends measuring blood pressure in both arms and repeating the measurements if there is a difference of more than 20 mmHg. If the difference remains, subsequent blood pressures should be recorded from the arm with the higher reading. NICE also recommends taking a second reading during the consultation if the first reading is above 140/90 mmHg. ABPM or HBPM should be offered to any patient with a blood pressure above this level.

If the blood pressure is above 180/120 mmHg, NICE recommends admitting the patient for specialist assessment if there are signs of retinal haemorrhage or papilloedema or life-threatening symptoms such as new-onset confusion, chest pain, signs of heart failure, or acute kidney injury. Referral is also recommended if a phaeochromocytoma is suspected. If none of these apply, urgent investigations for end-organ damage should be arranged. If target organ damage is identified, antihypertensive drug treatment may be started immediately. If no target organ damage is identified, clinic blood pressure measurement should be repeated within 7 days.

ABPM should involve at least 2 measurements per hour during the person’s usual waking hours, with the average value of at least 14 measurements used. If ABPM is not tolerated or declined, HBPM should be offered. For HBPM, two consecutive measurements need to be taken for each blood pressure recording, at least 1 minute apart and with the person seated. Blood pressure should be recorded twice daily, ideally in the morning and evening, for at least 4 days, ideally for 7 days. The measurements taken on the first day should be discarded, and the average value of all the remaining measurements used.

Interpreting the results, ABPM/HBPM above 135/85 mmHg (stage 1 hypertension) should be

To confirm the diagnosis of minimal change disease, a renal biopsy is necessary for this patient. The symptoms presented are not indicative of IgA nephropathy, post-infectious glomerulonephritis, or SLE, which typically present with a nephritic picture. While diabetic nephropathy can cause a nephrotic syndrome, the patient’s age and lack of diabetes symptoms make this unlikely.

Minimal change disease is a condition that typically presents as nephrotic syndrome, with children accounting for 75% of cases and adults accounting for 25%. While most cases are idiopathic, a cause can be found in around 10-20% of cases, such as drugs like NSAIDs and rifampicin, Hodgkin’s lymphoma, thymoma, or infectious mononucleosis. The pathophysiology of the disease involves T-cell and cytokine-mediated damage to the glomerular basement membrane, resulting in polyanion loss and a reduction of electrostatic charge, which increases glomerular permeability to serum albumin.

The features of minimal change disease include nephrotic syndrome, normotension (hypertension is rare), and highly selective proteinuria, where only intermediate-sized proteins like albumin and transferrin leak through the glomerulus. Renal biopsy shows normal glomeruli on light microscopy, while electron microscopy shows fusion of podocytes and effacement of foot processes.

Management of minimal change disease involves oral corticosteroids, which are effective in 80% of cases. For steroid-resistant cases, cyclophosphamide is the next step. The prognosis for the disease is generally good, although relapse is common. Roughly one-third of patients have just one episode, one-third have infrequent relapses, and one-third have frequent relapses that stop before adulthood.

Individuals who have recovered from DKA are susceptible to hypophosphataemia, which may cause weakness. The possibility of cerebral pontine myelinolysis is unlikely in this case, as the sodium levels have only been corrected by 5 mmol/l within a span of 2-3 days. While sepsis cannot be ruled out, there are no indications of focal signs. It is important to eliminate other potential diagnoses before considering anxiety as a possible cause.

Diabetic ketoacidosis (DKA) is a serious complication of type 1 diabetes mellitus, accounting for around 6% of cases. It can also occur in rare cases of extreme stress in patients with type 2 diabetes mellitus. DKA is caused by uncontrolled lipolysis, resulting in an excess of free fatty acids that are converted to ketone bodies. The most common precipitating factors of DKA are infection, missed insulin doses, and myocardial infarction. Symptoms include abdominal pain, polyuria, polydipsia, dehydration, Kussmaul respiration, and breath that smells like acetone. Diagnostic criteria include glucose levels above 11 mmol/l or known diabetes mellitus, pH below 7.3, bicarbonate below 15 mmol/l, and ketones above 3 mmol/l or urine ketones ++ on dipstick.

Management of DKA involves fluid replacement, insulin, and correction of electrolyte disturbance. Fluid replacement is necessary as most patients with DKA are deplete around 5-8 litres. Isotonic saline is used initially, even if the patient is severely acidotic. Insulin is administered through an intravenous infusion, and correction of electrolyte disturbance is necessary. Long-acting insulin should be continued, while short-acting insulin should be stopped. Complications may occur from DKA itself or the treatment, such as gastric stasis, thromboembolism, arrhythmias, acute respiratory distress syndrome, acute kidney injury, and cerebral edema. Children and young adults are particularly vulnerable to cerebral edema following fluid resuscitation in DKA and often need 1:1 nursing to monitor neuro-observations, headache, irritability, visual disturbance, focal neurology, etc.

The Royal College of Physicians (RCP) and NICE have published guidelines on the diagnosis and management of patients following a stroke. The guidelines provide recommendations for the management of acute stroke, including maintaining normal levels of blood glucose, hydration, oxygen saturation, and temperature. Blood pressure should not be lowered in the acute phase unless there are complications. Aspirin should be given as soon as possible if a haemorrhagic stroke has been excluded. Anticoagulants should not be started until brain imaging has excluded haemorrhage, and usually not until 14 days have passed from the onset of an ischaemic stroke. If the cholesterol is > 3.5 mmol/l, patients should be commenced on a statin.

Thrombolysis with alteplase should only be given if it is administered within 4.5 hours of onset of stroke symptoms and haemorrhage has been definitively excluded. There are absolute and relative contraindications to thrombolysis, including previous intracranial haemorrhage, intracranial neoplasm, and active bleeding. Mechanical thrombectomy is a new treatment option for patients with an acute ischaemic stroke. NICE recommends considering thrombectomy together with intravenous thrombolysis for people last known to be well up to 24 hours previously.

Secondary prevention recommendations from NICE include the use of clopidogrel and dipyridamole. Clopidogrel is recommended ahead of combination use of aspirin plus modified-release dipyridamole in people who have had an ischaemic stroke. Aspirin plus MR dipyridamole is recommended after an ischaemic stroke only if clopidogrel is contraindicated or not tolerated. MR dipyridamole alone is recommended after an ischaemic stroke only if aspirin or clopidogrel are contraindicated or not tolerated. Carotid artery endarterectomy should only be considered if carotid stenosis is greater than 70% according to ECST criteria or greater than 50% according to NASCET criteria.

IgA nephropathy, also known as Berger’s disease, is a type of glomerulonephritis that is characterized by persistent microscopic or recurrent macroscopic hematuria, often associated with upper respiratory tract infections. It is commonly linked to cirrhosis and coeliac disease, and elevated IgA levels are present in 50% of cases. Treatment is usually unnecessary unless renal function is affected, in which case an ACE inhibitor may be prescribed to control blood pressure. Immunotherapy has not been extensively studied. Dapsone, a medication used to treat leprosy and dermatitis herpetiformis, can cause hemolytic anemia and allergic reactions. Amyloidosis causes proteinuria and the nephrotic syndrome, while cryoglobulinemia is associated with hematological malignancies and connective tissue diseases and presents with cutaneous and articular manifestations. Renal cell carcinoma, which arises from the tubular epithelium, typically presents with painless hematuria and a palpable abdominal mass. For further information, refer to Lai K N et al.’s 2015 article on the treatment of IgA nephropathy in Kidney Disease (Basel).

Night sweats can be a symptom of various medical conditions. In a female patient, the differential diagnosis includes hypoglycemia, phaeochromocytoma, carcinoid, Hodgkin’s disease, tuberculosis, and thyrotoxicosis. Episodic bouts of sweating may suggest hypoglycemia, phaeochromocytoma, or carcinoid. However, if the patient reports night sweats, Hodgkin’s disease or tuberculosis should be considered. Hodgkin’s disease typically presents with localised lymphadenopathy, weight loss, pruritus, and fever. On the other hand, patients with thyrotoxicosis report constant sweating and heat intolerance, even without enlargement of the thyroid gland. In this case, considering the patient’s age and sex, thyrotoxicosis is the most likely diagnosis. Non-Hodgkin’s lymphoma and infection with an undefined organism are less likely causes, as there is no evidence of lymphadenopathy or abnormal blood tests. Phaeochromocytoma is also unlikely, as the patient does not have severe hypertension or other characteristic symptoms.

When selecting an intravenous fluid, dextrose is the preferred option. It is important to avoid sudden drops in glucose levels as this can cause a significant increase in osmolality, leading to cerebral edema and potential damage to the brain.

Diabetic ketoacidosis (DKA) is a serious complication of type 1 diabetes mellitus, accounting for around 6% of cases. It can also occur in rare cases of extreme stress in patients with type 2 diabetes mellitus. DKA is caused by uncontrolled lipolysis, resulting in an excess of free fatty acids that are converted to ketone bodies. The most common precipitating factors of DKA are infection, missed insulin doses, and myocardial infarction. Symptoms include abdominal pain, polyuria, polydipsia, dehydration, Kussmaul respiration, and breath that smells like acetone. Diagnostic criteria include glucose levels above 11 mmol/l or known diabetes mellitus, pH below 7.3, bicarbonate below 15 mmol/l, and ketones above 3 mmol/l or urine ketones ++ on dipstick.

Management of DKA involves fluid replacement, insulin, and correction of electrolyte disturbance. Fluid replacement is necessary as most patients with DKA are deplete around 5-8 litres. Isotonic saline is used initially, even if the patient is severely acidotic. Insulin is administered through an intravenous infusion, and correction of electrolyte disturbance is necessary. Long-acting insulin should be continued, while short-acting insulin should be stopped. Complications may occur from DKA itself or the treatment, such as gastric stasis, thromboembolism, arrhythmias, acute respiratory distress syndrome, acute kidney injury, and cerebral edema. Children and young adults are particularly vulnerable to cerebral edema following fluid resuscitation in DKA and often need 1:1 nursing to monitor neuro-observations, headache, irritability, visual disturbance, focal neurology, etc.