Medicine C Flashcards

Question

Which drugs require special consideration when used in renal impairment?

Answer 1

Lithium is a mood stabiliser mainly used in bipolar disorders. It has a narrow therapeutic index and 100% renal clearance. Toxicity can cause hypothyroidism, renal impairment, and benign intracranial hypertension. The BNF advises caution in mild to moderate renal impairment and avoidance in severe renal impairment. Serum lithium monitoring should be done. Gentamicin is an aminoglycoside antibiotic used for the treatment of serious, Gram negative, bacterial infections. It has a narrow therapeutic index and is primarily renally cleared. Toxicity include nephrotoxicity and ototoxicity. The BNF advises prolonged dosing intervals without dose reduction. Therapeutic drug monitoring should also be done. Enoxaparin is used for the treatment and prophylaxis of thrombosis and has a narrow therapeutic index. There is a 70% renal clearance and toxicity causes an increased risk of bleeding. Unfractionated heparin has a greater molecular weight and is not filtered. The BNF advice is to use unfractionated heparin instead if renal impairment.

Answer 2

Warfarin is an oral anticoagulant used to prevent thrombus formation. It antagonises the effects of vitamin K and the effect of warfarin is measured by monitoring INR. The main adverse effect is haemorrhage and there is a potential for reduced metabolism of CYP2C9 in severe hepatic impairment. However, main risk is already reduced clotting factor synthesis and Vitamin K effect in hepatic impairment. The BNF advises caution in mild and moderate hepatic impairment but avoidance in severe impairment. Paracetamol is an analgesic with known dose-dependent hepatotoxicity in overdose leading to hepatocellular necrosis. Toxicity occurs when the glucuronidation and sulfation pathways are saturated. This increases the proportion converted to the toxic metabolite NAPQI and protective pathways are saturated at lower doses in hepatic impairment. BNF advice is caution in hepatic impairment.

Answer 3

Polypharmacy causes increased drug interactions, adverse effects, increased falls, hospital admissions, length of hospital stay, hospital readmission and mortality. Whether it is an independent factor is debatable. 30% of hospital admissions in the over 65s are caused by adverse drug reactions. These can be divided into: - Type A: High morbidity but low mortality and thus potentially preventable - Type B: Idiosyncratic/strange responses which could not have been predicted

Answer 4

It is important that normal ageing is not medicated. Age related muscle weakness, balance difficulty, social stress in widowhood or loneliness, and gravitational oedema caused by prolonged sitting should not be treated with medication. Non-pharmacological methods should be considered instead such as sleep hygiene, social prescribing, hydration, CBT, yoga, group exercise, compression stockings and diet.

Answer 5

Antiplatelets (aspirin), diuretics, NSAIDs, anticoagulants, opioids, beta-blockers, ACE-I/ARBs, and hypoglycaemic agents.

Answer 6

The prescribing cascade is where a drug is prescribed, a drug reaction is misdiagnosed and so further drugs are prescribed to manage that symptom. For example, a cholinesterase inhibitor causes incontinence which is then treated with an anticholinergic. Aggravating factors for the cascade include inadequate information provided to patients, multiple care providers, and poor communication.

Answer 7

Older people generally have a declining renal function as there is a 50% glomerular filtration loss between age 20 and 90. There is also a reduced liver mass and metabolic capacity by 25-35%. Skeletal body mass will also reduce as there is an increased ratio of body fat to body water. Changes in drug absorption occur because there is an increased gastric emptying time which reduces oral bioavailability, and increased gastric pH with reduced gastric acid production thus the breakdown of enteric coatings is slower, and decreased active transport mechanisms in the gut for calcium, folate, and B12. Increased gastric pH increases the absorption of methyldopa. The reduced skeletal mass with an increased ratio of body fat to water has an impact on the volume distribution of water-soluble drugs (decreasing distribution so increasing serum concentration) such as paracetamol and digoxin. Whereas fat-soluble drugs have an increased volume distribution so prolonged half-life and thus more toxicity. This is seen in diazepam, amiodarone, and verapamil. The decreased albumin levels cause an increased free fraction of highly albumin-bound drugs such as warfarin and phenytoin however, an increased free fraction leads to increased clearance. Finally, there is also increased penetration across the blood-brain barrier in older people for many drugs. The reduced liver mass causes reduced oxidative metabolism. This means there is a prolonged half-life and a higher steady-state concentration of some drugs (diazepam, metoprolol, and phenytoin). There is unchanged conjugative metabolism in the liver. The decreased portal venous blood flow affects drugs with a high hepatic extraction ratio, reducing first-pass metabolism and increasing drug concentration (morphine and verapamil). The decreased renal function in elderly patients is the most important aspect of pharmacodynamic changes. The reduced glomerular filtration rate affects drugs like aminoglycosides. The reduced tubular function reduces the active tubular excretion of drugs like beta-lactam antibiotics. There is increased susceptibility to nephrotoxic drugs such as ACE-I/ARD, diuretics, and NSAIDs. Acute illness (dehydration) can rapidly reduce renal clearance which is important in drugs with a narrow margin between therapeutic and toxic doses (digoxin).

Answer 8

There is increased sensitivity to toxic effects of drugs due to diminished physiological reserves. There are also decreased homeostatic mechanisms which means decreased ability to compensate for physiological challenges offered by drug therapy. The increased sensitivity to toxic effects is seen in anti-cholinergic side effects of tricyclic antidepressants such as constipation and confusion. There are also increased adverse effects with anticoagulants as the frequency of bleeding events increases with age. There is a 50% increased sensitivity to opiates and a marked increase in sensitivity to CNS depressants such as propofol. The decreased homeostatic mechanisms cause postural hypotension in response to vasodilators. There is also a combination of diminished baroreceptor reflexes and impaired cardiac conduction increases susceptibility to bradyarrhythmia and hypotension in response to verapamil and diltiazem. The STOPP and START criteria are a tool for reducing inappropriate prescribing in the elderly. The BNF is also a good source of information. According to age and frailty the dose should be adjusted, commonly 50% of the adult dose. In terms of formulation it is important to consider once daily or once weekly formulations and used a fixed dose combination where possible. Write full instructions on every prescription and avoid terms like ‘as directed.’ Child resistant containers may be unsuitable and in cognitive impairment the use of bubble packs or family assistance is required. Drugs which should be avoided include NSAIDs (GI haemorrhage, renal impairment and hypertension), Benzodiazepines (falls), anticholinergics (unmasking Alzheimer’s disease and urinary retention), tricyclic antidepressants (orthostatic hypotension and sedation), Glibenclamide (hypoglycaemia) and Doxazosin (orthostatic hypotension, dry mouth, and urinary problems). Drugs that can be appropriate to add include anticoagulants in AF, ACE inhibitors and Beta blockers in left ventricular dysfunction, statins in IHD, and bisphosphonates in osteoporosis. Medication reviews for older people should be every 12 months for 1-3 drugs and every 6 months if 4 drugs or more. Stop drugs that are not indicated. Doses should be reduced as renal function declines and treat new conditions with care.

Answer 9

This can be defined as simultaneous and long-term use of different drugs by the same individual. The standard definition is 5 or more medicines in an adult daily and in children it is 2 or more. Severe polypharmacy/hyper polypharmacy is more than 10 medicines. Sometimes polypharmacy is clinically appropriate. It is problematic when patients are taking medications that they no longer need, where the benefit of a medication does not outweigh the harm, where there are significant drug interactions, or when the medicines cannot be managed by the patient. The prescribing cascade occurs when side effects of one drug are not recognised so additional drugs are prescribed to deal with the new symptom. The two biggest risk factors are older age and multi-morbidity

Answer 10

Deprescribing is defined as the ability to “identify and discontinue drugs when existing or potential harms outweigh existing or potential benefits within the context of an individual patient’s care, functional status, life expectancy, values, or preferences.”

Answer 11

Medicinal optimisation is to help patients improve their outcomes, take their medicines correctly, avoid taking unnecessary medicines, reduce wastage of medicines and improve medicine safety. Patients who should be prioritised for deprescribing and optimisation should be those taking over 10 medicines and those taking between 4-9 medicines with other unfavourable factors (Contraindications, drug-drug reactions, and adherence problems). NHS Scotland say those who should be prioritised are the over 50s in a care home, approaching end of life care, prescribed 10 or more medicines or on high risk medications regardless of the number of medicines taken. To avoid this problem there should be regular medication reviews in GP practices. The main tool use is the STOPP/START guideline (Screening Tool of Older People’s potentially inappropriate Prescriptions/Screening Tool to Alert doctors to Right Treatments). This includes 80 STOPP and 34 START criteria.

Answer 12

Infection, tumour, and glomerular dysfunction

Answer 13

Intravascular haemolysis

Answer 14

Rhabdomyolysis

Answer 15

Dysmorphic erythrocytes on microscopy indicates passing through the glomerular membrane and hence indicates glomerular disease. This is supported by the presence of red cell casts which are developed in the tubular system. A repeat dipstick should be done to prove this is persistent rather than transient. Causes include cysts, tumours, glomerulonephritis, small-vessel vasculitis, SLE, other glomerular disease, interstitial nephritis, trauma, pyelonephritis, calculus, polyarteritis nodosa, vascular malformation, renal infarction, coagulation disorders, cystitis, BPH, and urethritis. If the patient is elderly, more sinister causes should be suspected such as cancers. Signs of infection should be considered. If the patient displays signs of multisystem disease then consider autoimmune conditions.

Answer 16

ACR vs PCR (Albumin creatinine ratio vs Protein creatinine ratio): The threshold for significant proteinuria is 1g in 24 hours. If the ACR is above 70 or PCR over 100 then this is significant and highly suggestive of intrinsic renal disease. Less than this (70 or 100) can indicate multi-system disease or chronic changes for hypertension or diabetes.

Answer 17

The quantification of protein leakage in the urine can be used to distinguish between nephrotic and nephritic syndrome. Persistent haematuria with only moderate or mild proteinuria is indicative of nephritic sediment which is caused by inflammation, reactive cell proliferation, breaks in the GBM and crescent formation (autoimmune anti-GBM, post-streptococcal glomerulonephritis or small vessel vasculitis). Clinical features include haematuria, oedema, hypertension, oliguria and reduced renal function. Nephrotic syndrome on the other hand will have microscopic haematuria with significant proteinuria (over 70 ACR or 100 PCR). Clinical features are overt proteinuria, hypoalbuminemia, oedema and generalised fluid retention, and possible intravascular volume depletion with hypotension or intravascular volume expansion with hypertension. Nephrotic syndromes are caused by injuries to the podocytes or changed architecture as seen in scaring or deposition of matrix. Most glomerular diseases are immunologically mediated. The nature of the blood streams immunology can indicate the cause of the glomerular disease. Therefore antibody test are used to confirm the diagnosis of the following diseases: Any patient presenting with Haematoproteinuria should also be investigated with blood tests for circulating antibodies. Goodpasture’s syndrome is anti-GBM.

Answer 18

Mechanism: This is seen in both type 1 and 2 diabetes and affects 1/3 after 20 years. Risk factors include poor glycaemic control, long duration of diabetes, presence of other microvascular complications, Asian or Pima Indian, pre-existing hypertension, family history of nephropathy or hypertension. The clinical course is hyperfiltration leading to falling creatinine and rise in glomerular filtration rate. This makes it look like improved kidney function, but it is caused by local vasoactive factors increasing blood flow to the glomerulus and enlarging the kidneys. However, there will also be increased ACR showing histological damage but function will not be impaired until the patient has developed hypertension whereby there will be a slow decline. The pathophysiology is not fully understood however there is thought to be activation of the RAAS system leading to both intrarenal and systemic effects. There may also be a direct toxic effect of prolonged hyperglycaemia leading to renal inflammation and fibrosis. Podocytes are injured and so change charge, since they are the barrier for proteinuria the presence of proteinuria is the hallmark of nephropathy with or without loss of renal function owing to glomerulosclerosis. Hyalinosis and sclerosis = glomerulosclerosis. This is the irreversible loss of neprhrons and hence a decreased GFR. As a consequence of endothelial or capillary wall injury, plasma proteins leak into the extracellular glomerular structures. Hyalinosis is the accumulation of material that is homogenous and eosinophilic by light microscopy. These deposits may obliterate the capillary lumens of the glomerular tuft. Hyalinosis is the end result of various forms of glomerular damage. Sclerosis is characterised by the deposition of extracellular collagenous matrix. It may be confined to mesangial areas or involve the capillary loops, or both. The sclerosing process may also result in obliteration od some or all of the capillary lumens in affected glomeruli.

Answer 19

The pathophysiology is not understood. Hypertension can be causative (hypertensive nephrosclerosis) or a contributory factor towards the development of kidney disease. HTN is present in over 80% of patients with CKD. The more advanced renal impairment the more likely the patient has HTN. The worse the HTN the worse the CKD. The kidneys control BP through the RAAS. Increased activity of the RAAS is often partly responsible for HTN, especially in patients with vascular disease because renal ischaemia stimulates renin secretion. There could be a role of sodium retention contributing to HTN and enhanced activity of the sympathetic nervous system (the afferent signal may arise in part within the failing kidneys since it is not seen in patients who have undergone bilateral nephrectomy). Once again, sclerosis of renal arterioles and small arteries is strongly associated with HTN, which can both be a cause and a consequence of nephrosclerosis. The affected vessels have thickened walls and consequently narrowed lumens which results in focal parenchymal ischaemia. Ischaemia leads to glomerulosclerosis and chronic tubulointerstitial injury. There are two processes which participate in arterial lesions: 1. Medial and intimal thickening, as a response to haemodynamic changes, ageing, genetic defects, or some combination of these 2. Hyalinization of the arteriolar walls, caused by extravasation of plasma proteins through injured endothelium and by increased deposition of basement membrane matrix (similar to diabetic nephrosclerosis). Diabetes and HTN are the most common causes of CKD and are essentially unsuccessful wound healing following chronic sustained injury with endothelial damage. They are progressive diseases. The final common pathway is renal fibrosis (glomerulosclerosis, tubular atrophy and interstitial fibrosis). This leads to low GFR and proteinuria.

Answer 20

This is a rare multi-system autoimmune connective tissue disease which mainly occurs in women. Onset is usually between 20-30. Many of the target antigens are intracellular or intranuclear and the triggers for the autoantibody production are unclear. Symptoms are variable and can include malar rash, discoid rash, photosensitivity, oral ulcers, arthritis, pleuritis or pericarditis, persistent proteinuria (over 0.5g a day or red cell casts), seizures, psychosis, haemolytic anaemia, raised anti-DNA antibodies or Sm antibodies or anti-phospholipid antibodies. There may also be an abnormal ANA titre by immunofluorescence. The histological classification of Lupus Nephritis: Class: 1. Minimal mesangial LN 2. Mesangial proliferative LN 3. Focal LN 4. Diffuse LN 5. Lupus membranous GN 6. Advanced sclerosing LN

Answer 21

It seems that renal involvement in SSc is primarily characterized by vascular damage and glomerular hypofiltration, which is quite different from patients with diabetic or hypertensive nephropathy, where hyperfiltration and increased glomerular capillary pressure represent the major causes of progressive renal dysfunction

Answer 22

The exact mechanisms by which Sjögren's syndrome causes renal damage are not fully understood, but several possible factors have been proposed: Immune Complex Deposition: In Sjögren's syndrome, the immune system mistakenly attacks the body's own tissues, including the kidneys. This can lead to the formation and deposition of immune complexes in the renal tissues. The immune complexes can trigger an inflammatory response, leading to damage to the kidney's filtering units, known as glomeruli. Tubulointerstitial Nephritis: Sjögren's syndrome can cause inflammation in the tubules and interstitium of the kidneys, a condition known as tubulointerstitial nephritis. This inflammation can impair the normal functioning of the tubules, affecting the reabsorption and excretion of water, electrolytes, and waste products. Over time, chronic inflammation can lead to progressive renal damage. Vascular Involvement: Sjögren's syndrome can affect the blood vessels within the kidneys. The inflammation and immune dysregulation associated with the condition can lead to vasculitis, which is inflammation of the blood vessels. Vasculitis can disrupt the blood supply to the kidneys, impairing their function and potentially causing tissue damage. Antibody-Mediated Damage: In some cases, individuals with Sjögren's syndrome may develop autoantibodies, such as anti-SSA (Ro) and anti-SSB (La) antibodies. These antibodies can circulate in the bloodstream and may deposit in the kidneys, leading to kidney damage through mechanisms such as complement activation and immune cell recruitment.

Answer 23

Multiple myeloma is a haematological malignancy known as plasma cell dyscrasia. It is defined by a proliferation of malignant plasma cells. It is the second most common haematological malignancy behind non-Hodgkin’s lymphoma. These malignant plasma cells produce immunoglobulins and there are 4 typical clinical criteria: Hypercalcaemia (osteolytic process), renal impairment (immunoglobulin deposits causing an enlarged kidney), anaemia and bone disease. They are called the CRAB criteria. AKI is common in myeloma, 30% of individuals at time of diagnosis, and is mainly due to nephrotoxic effects of abnormal immunoglobulins. It is often irreversible and may present as light chain cast nephropathy, light chain deposition disease or AL amyloidosis. Light chain cast nephropathy: Light chains are usually reabsorbed in the proximal tubules but in MM there is an excessive production which exceed the tubular reabsorption capacity. The light chains the bind to proteins in the tubular system and form intratubular casts. This causes inflammation and fibrosis and direct tubular injuries thus an AKI develops. Light chain deposition disease: This is less common, and the difference is that the light chains are deposited in the glomeruli causing damage rather than in the tubular system. AL amyloidosis: This is deposition of amyloid fibrils of light chains. However, some of the other process of the CRAB MM presentation can cause AKI such as hypercalcaemic nephropathy whereby bone resorption causes hypercalcaemia and thus tubular damage through excess calcium. Furthermore, the treatment of MM causes tuourlysis which can damage the kidneys through tubular crystallization of uric acid.

Answer 24

Cryoglobulinemia is a rare medical condition characterized by the presence of abnormal proteins called cryoglobulins in the blood. Cryoglobulins are immunoglobulins (antibodies) that clump together and precipitate in cold temperatures, which can lead to inflammation and damage in various organs and tissues of the body. The most common symptoms of cryoglobulinemia include: Skin manifestations: Such as purpura (purple-colored spots or patches), ulcers, and Raynaud's phenomenon (fingers and toes becoming pale or bluish in response to cold). Joint pain and swelling: Arthralgia and arthritis-like symptoms. Kidney involvement: Glomerulonephritis (inflammation of the kidney's filtering units) may occur, leading to proteinuria (excessive protein in the urine) and impaired kidney function. Peripheral neuropathy: Nerve damage resulting in numbness, tingling, and weakness in the extremities. Fatigue, weakness, and general malaise.

Answer 25

It is characterized by the combination of three major features: hemolytic anemia (destruction of red blood cells), thrombocytopenia (low platelet count), and acute kidney injury. HUS is most commonly caused by certain strains of bacteria, particularly a strain of Escherichia coli (E. coli) known as E. coli O157:H7. This strain produces toxins that can lead to damage to blood vessels, especially in the kidneys. Other infections, such as certain types of pneumonia, may also cause HUS. The condition primarily affects children, although it can occur in people of any age. It often starts with gastrointestinal symptoms, such as diarrhea (which may be bloody), abdominal pain, and vomiting. These symptoms may be followed by the onset of the characteristic triad of symptoms: hemolytic anemia, thrombocytopenia, and kidney injury.

Answer 26

The development of sickle cell nephropathy (SCN) typically occurs in childhood as seen in the appearance of hyperfiltration and proteinuria. Both are primarily caused by the polymerization of sickle cells in the kidney microvasculature due to the low O2 tension, high osmolarity, and low acidity. This polymerization fills and occludes blood vessels such as the vasa recta in the kidneys leading to microinfarctions, leakage into surrounding tissues and potentially papillary necrosis and renal infarcts. Renal papillae are especially susceptible to damage eventually causing papillary necrosis since these vessels are only supplied with blood by the vasa recta. The sickling of the cells also contribute to two other mechanisms which are chronic hypoxia and chronic hemolysis.

Answer 27

ANCA vasculitis is an autoimmune disease which causes swelling/inflammation of the blood vessels. The vasculitides are defined by the presence of inflammatory leukocytes in vessels walls with reactive damage to mural structures. Vasculitis can present with multiple symptoms involving multiple systems which at first glance do not appear related. ANCA vasculitis is defined by the presence of anti-neutrophil cytoplasmic antibodies in the blood and it is a small vessel vasculitis. ANCA antibodies (previously known as Wegner’s disease) are specific antibodies for antigens in the cytoplasmic granules of neutrophils and monocyte lysosomes. These antibodies can be detected with indirect immunofluorescence microscopy. Two major patterns of staining are present: Cytoplasmic ANCA (c-ANCA) and peri-nuclear ANCA (p-ANCA). Patients can have ANCA vasculitis and be ANCA negative. When ANCA stimulated neutrophils attack small blood vessels they cause inflammation and there is an unchecked immune cell response with associated cytokine storm which damages the vessel walls and results in ischaemic damage to the organs supplied by the affected vessels. The ANCA antibody amount does not relate to the extent of the disease. The symptoms depend on the vessel affected: The vasculitis rash presents with small red-purple spots that are slightly raised and usually found in the lower extremities. ANCA vasculitis which involves the lung is very dangerous and can cause pulmonary haemorrhage. On CXR there may be transient alveolar-type infiltrates in a peripheral distribution and occasionally nodular lesions. : Inflammation and necrosis of the renal blood vessels causes kidney disease. This causes rapidly progressive glomerulonephritis (RPGN) and hence AKI. RPGN is a syndrome of glomerular haematuria (red blood cell casts or dysmorphic red blood cells), rapidly developing AKI over weeks to months and focal glomerular necrosis with or without glomerular crescent development on renal biopsy. The crescent is an aggregate of macrophages and epithelial cells in the Bowman’s space. Other small vessel vasculitis which can affect the kidneys include granulomatosis with polyangiitis, microscopic polyangiitis, renal-limited vasculitis and eosinophilic granulomatosis with polyangiitis (ANCA negative) which is otherwise known an Churg-Strauss syndrome.

Answer 28

The renal blood screen includes ANCA, GBM, C3/C4, ANA, dsDNA, Serum immunoglobulins, myeloma screen, serum free light chains, urine BJ proteins, and hepatitis/HIV screen.

Answer 29

A kidney biopsy should be taken from the lower 1/3 of the kidney. A kidney biopsy has three stages: 1. Hematoxylin-eosin stain for mesangial expansion or hypercellularity 2. Immunofluorescent microscopy for IgA deposition or other antibodies within the glomerular mesangium 3. Electron microscopy for significant expansion of the mesangial matrix and presence of large mesangial dense deposits.

Answer 30

IgA nephropathy is the most common glomerulonephritis in developed countries. It is sometimes referred to as Berger’s disease. It is most common in Caucasians and east Asians and usually manifests between 20-30. It is twice as common in males. It commonly presents as visible haematuria accompanied with an URTI (synpharyngitic haematuria) and associated loin pain. Occasionally it presents as asymptomatic haematuria and mild proteinuria. Very rarely it presents with AKI and nephrotic syndrome. Tamm-Horsfall proteins are not detected on a urine dipstick. Bence Jones proteins are detected in the urine and are a sign of myeloma. Tubular damage causes the capacity of the tubules to reabsorb to be reduced. IgA nephropathy pathophysiology: There may be genetic susceptibility, but most patients start with a respiratory infection and abnormal stimulation of lymphoid organs. This causes an overproduction of B cells and abnormally glycated IgA antibodies. The abnormal glycated IgA causes them to create immune complexes which IgA does not normally do. This is then deposited in the kidneys. This causes endothelial damage, loss of mesangial proliferation and endothelial proliferation and thus haematuria, proteinuria, and kidney failure. There may also be complement activation which causes more damage. Diagnosis is made with kidney biopsy. Indications for biopsy are proteinuria and haematuria or haematuria with deteriorating renal functions.

Answer 31

This can be caused by cirrhosis or severe liver disease, HIV, coeliac disease, Crohn’s, UC, lymphoma, ankylosing spondylitis, and small cell cancers. If you treat the primary cause then you treat the IgA nephropathy.

Answer 32

This is a genetic disease which usually presents with hearing difficulties. In the kidneys it causes an uneven thickness of the glomerular basement membrane with deposits in between. Overall, it is a relatively thinner basement membrane. Patients will go into end stage renal failure.

Answer 33

Thin membrane diseases have a uniform thinness of the glomerular basement membrane and no deposits in-between. This is benign but some red cells will pass into the urine. The OXFORD classification is used to prognosticate the progress from an IgA nephropathy (MEST-c): The further down the higher the treatment level required. M – Mesangial hypercellularity E – Endothelial hypercellularity S – Segmental glomerulosclerosis T – Tubular atrophy/interstitial fibrosis C – Crescent formation Prognostic factors are BP >140/90, decline in renal function and persistent proteinuria >1g/day

Answer 34

Non-immunosuppressive therapy: Lifestyle measures, BP <130/80, ACE-I even if BP is controlled, lipid lowering therapy (SHARP trial) and fish oil. Steroids should not be used unless there is rapidly declining renal function or there is crescent formation. Minimal change nephropathies on the other hand respond very well to steroids.

Answer 35

Non-immunosuppressive therapy: Lifestyle measures, BP <130/80, ACE-I even if BP is controlled, lipid lowering therapy (SHARP trial) and fish oil. Steroids should not be used unless there is rapidly declining renal function or there is crescent formation. Minimal change nephropathies on the other hand respond very well to steroids. These include antiphospholipid syndrome, sjogren's, SLE, polymyositis, dermatomyositis, diffuse systemic sclerosis, and limited systemic sclerosis.

Answer 36

This is a connective tissue disease characterised by fibrosis (skin and internal organs), vascular abnormalities (vasospasm, ischaemia and vessel intimal hyperplasia resulting in organ disease) and autoimmunity (ANA, Scl70, anticentromere and anti RNA polymerase). Clinical features include thickening in two distinct subtypes: 1. Limited (distal to elbows, knees and neck) 2. Diffuse (involving more proximal skin) Systemic sclerosis can cause sclerodactyly which is thickening over the fingers which can cause contractures. It often spreads proximally from here. The skin thickening can be hyperpigmented. Vascular phenomenon seen in systemic sclerosis include Raynaud’s phenomenon and digital ulceration. Raynaud’s can occur in the ears and nose. In the rewarming phase of Raynaud’s, the skin can become itchy and painful. Interstitial lung disease is a late stage finding of systemic sclerosis and is associated with both diffuse and limited disease. It occurs earlier in the disease course of diffuse SS. Diffuse SS patients are particularly at risk of renal complications of accelerated hypertension and proteinuria. Pulmonary artery hypertension is a late complication that is more commonly seen in limited disease. One of the most common complications of SS is involvement of the GI tract which can presents as reflex, dysphagia, orodental complications, weight loss, malnutrition, distention and bloating, anaemia, diarrhoea, exocrine pancreatic insufficiency, constipation and anorectal incontinence. Common co-morbidities include Barrett metaplasia, rectal prolapse, diverticular disease and sigmoid volvulus.

Answer 37

This is a connective tissue disease characterised by multiorgan involvement. There is an association with clotting disorders and obstetric complications. Patients commonly have Oro mucosal ulceration and secondary Sjogren’s. The autoimmune profile associated with SLE includes: - ANA positive (not diagnostic) - dsDNA - Smith antibody - Ro and La antibody (mainly seen in Sjogren’s) There is often unusual scarring including scarring with alopecia. Common rash is butterfly/malar which spares the nasolabial folds. Haematology: Patients typically have a normocytic anaemia, lymphopenia, thrombocytopenia, hypocomplementaemia, polyclonal increase in immunoglobulins and raised ESR with normal CRP. The association with clotting disorders includes lupus anticoagulant, antiphospholipid antibodies and anti B2glycoprotein antibodies. These are procoagulant hence cause obstetric complications. Livedo reticularlis describes a lace like pattern of rash on the legs which is usually seen in patients with antiphospholipid syndrome associated with SLE. It is a significant finding when the rash does not disappear on rewarming – this is then called Livedo racemosa. This is common in the normal population but will resolve on rewarming. The SLE arthritis is unique as the arthritis presents with significant deformity such as swan neck deformity which is reversible, unlike RA. The problem is ligamentous rather than damage to the joints. Systemic features in SLE include fatigue, low grade fevers, weight change and myalgia. They are very common.

Answer 38

This is an autoimmune condition which attacks exocrine glands and hence causes dry eyes, dry mouth, dry vagina, and dry skin. Dry eyes and dry mouth is known as keratoconjunctivitis sicca. Gland swelling is common and usually transient however patient is at increased risk of lymphoma so persistent gland swelling should be investigated. Extra glandular features include dysphagia, abnormal GI motility, interstitial gum disease, fits, hemiplegia, ataxia, cranial nerve lesions, interstitial lung diseases, renal tubular acidosis, Raynaud’s, palpable purpura, arthralgia, sensory neuropathy and mononeuritis multiplex.

Answer 39

These are autoimmune inflammatory myositis. Myositis is inflammation within the muscle and thus there is muscular discomfort, discomfort on palpation and weakness of the muscle. These are the cardinal features of myositis. Some patients will have additional skin involvement such as Gottron papules which are erythema over the knuckles, DIPs, and PIPs with myositis. Dilated nailfold capillaries can be associated with many connective tissue diseases. There may be a violatious rash over the eyelids or calcinotic deposits on X-ray (seen in both SS and myositis). Extra-muscular manifestations of myositis include interstitial lung disease and arthritis. Anti-synthetase syndrome is where patients have a myositis, features of arthritis, interstitial lung disease and deep fissuring on the skin of the hands (mechanic’s hands) and raynaud’s phenomenon. Autoantibodies: - Anti-synthetase syndrome: Anti ARS, Anti Jo-1, Anti PL-7, Anti PL-12, Anti OJ, Anti EJ and Anti KS - Dermatomyositis malignancy: Anti Mi-2, Anti TIF1-y, Anti NXP2, Anti SAE, and anti MDA5 - Statin associated myopathy: Anti HMGCR (reversible when statin stops normally unless these antibodies persist) - Severe resistant disease: Anti SRP Dermatomyositis is commonly seen in children and when it appears in adults it presents with a malignancy. Malignancy is often detected 2-3 years after diagnosis and often include GI, lung, ovary, and lymphatic tumours. The risk persists throughout the patient’s lifetime. It is associated with the anti TIFg antibody so antibody negative patients should be suspected for malignancy.. Some other dermatomyositis antibodies are associated with malignancy, especially anti TIF1-y. All inflammatory myositis are treated with steroids and immunosuppression. Life threatening manifestations of inflammatory myositis include dysphagia and breathing compromise due to weakness of respiratory muscles.

Answer 40

Giant cell arteritis (GCA) is a large vessel vasculitis. It typically presents over the age of 50 with temporal headaches, scalp tenderness, visual disturbance (diplopia, amaurosis fugax and visual loss), tongue/jaw claudication and raised inflammatory markers (ESR and CRP as ESR can be misleading). If the patient is under 50 it should be considered very unlikely. GCA is commonly associated with Polymyalgia rheumatica and thus can also have shoulder pain and pelvic girdle stiffness, early morning stiffness, scalp infarction, limb claudication and features of cerebral ischaemia. If a patient presents with the clinical features of GCA then steroids must be started immediately, pending investigation. Potential complications include vision loss and cerebral ischaemia. The immediate management is with: - prednisolone 40mg OD if no visual disturbance or jaw claudication - 60mg OD if visual disturbance or jaw claudication - Consider IV methylprednisolone 500-1000mg up to three doses if there are signs of cerebral ischaemia or vision loss. Visual symptoms should be referred urgently to Ophthalmology and then referred to Rheumatology. Arrange an urgent inflammatory markers screen including CRP and ESR. Further investigations include temporal artery USS, temporal artery biopsy and if evidence of a non-cranial large vessel vasculitis, then consider MRA or CTA. Long term management is with long term steroids (12-18 months gradually tapered down). This should also include bone prophylaxis, gastroprotection and screen for steroid complications including diabetes. Monitoring progress is with symptoms assessment and inflammatory markers. Significant relapse in symptoms should provoke an increase in steroid dose to last known stable dose. Tocilizumab is an interleukin-6 receptor antibody which is indicated if biopsy or imaging prove GCA. It is only used for refractory or relapsing disease and can reduce the steroid burden for patients with GCA.

Answer 41

Granulomatosis with polyangiitis is cANCA associated and will have lung involvement (ILD and cavitating lesions), renal involvement and rashes. ENT involvement is erosive and there may be peripheral nerve damage. Eosinophilic granulomatosis with polyangiitis is pANCA associated with lung involvement (ILD and late onset of Asthma), renal involvement and rashes. ENT involvement is allergic and there may be peripheral nerve damage. There can be eosinophilia-pneumonitis or in the blood stream (this is transient).

Answer 42

Inflammatory: Stiffness worse in the morning, swelling that is warm/red, symptoms improve with activity, systemically unwell, boggy swelling, spares the DIPJs, spares hips and spine, and is symmetrical. Mechanical: Stiffness that persists, swelling that isn't hot or red, symptoms improve with rest, systemically well, cool bony swelling, and asymmetrical. Inflammatory arthritis can be defined by whether it is peripheral or axial. Autoinflammatory conditions underpin the spondyloarthropathies and the produce pro-cytokines whereas RA is an autoimmune disease.

Answer 43

Rheumatoid Arthritis is more common in women and had occur at any age though median is 58. There is an additional risk for women who have not given birth and a reduced risk for women who have breastfed. Smoking increases the risk of severe erosive disease, even childhood exposure to cigarettes. A family history is associated with HLA DRB1. Other risk factors include obesity, diet, and alcohol. The pattern of joint disease in RA is small joints of the hands and feet whilst sparing the DIP joints. It tends to spare the spine except for the neck. The disease can begin in one place but by a process of additive joint involvement more will become involved. Others will have palindromic attacks where one or more joints flare and settle spontaneously over weeks. This pattern may occur for a while before developing a persistent inflammation. Many patients will report chest infections before their flare up but this does not indicate a reactive arthritis. RA is symmetrical, polyarticular and affects small joints. Synovitis presents with warm, tender, and swollen joints. Even in early disease patients can develop wasting of the intrinsic hand muscles and poor grip strength. Deformity is a late-stage sign. Investigations include an anti-CCP antibody, not Rheumatoid factor. RF is an IgM antibody targeted against the fixed chain portion of IgG. 70-80% are RF positive but the specificity reduces as people age. It is prognostic for worse disease. Anti-CCP is an important prognostic indicator with seropositive patients having more aggressive erosive disease. Anti-CCP is more sensitive and more specific than RF. Patient should be referred to rheumatology early! Investigations for a patient with suspected RA should include: - FBC (Normochromic normocytic anaemia, thrombocytopaenia, thrombocythemia, or lymphopenia) - LFTs and U&Es to provide baseline for potential treatments - CRP and ESR – Will both be raised - Immunology – RF and anti-CCP for prognostic reasons - Urine dip – connective tissue disease or vasculitis - Plain X-ray of hands, feet, and chest (checking for erosive disease as a marker of aggressive disease. CXR may show arthritis changes, old infection (TB), cancers and hilar lymphadenopathy suggesting other pathology) - Joint USS (diagnose early inflammation) - If there is a unilateral hot swollen joint, then consider a joint aspirate

Answer 44

Radiographic changes in RA: 1. Juxta-articular osteopaenia 2. Erosions 3. Joint space narrowing 4. Soft tissue swelling 5. Joint effusion 6. Deformity Radiographic changes for osteoarthritis: 1. Non-uniform joint space loss 2. Osteophyte formation 3. Cyst formation 4. Subchondral sclerosis

Answer 45

Treatment should be holistic, and patient centred. This means an MDT approach involving the specialist nurses, physiotherapy, OTs and podiatry. The aim is low disease activity or remission as measured by the DAS-28. Pharmacological management: 1. NSAIDs and analgesia (naproxen) 2. Steroids (often IM methylprednisolone or intra-articular) 3. Conventional DMARDs (Methotrexate, sulphasalazine, hydroxychloroquine, and leflunomide) 4. Targeted therapies (Anti-TNF, Anti-IL6, Anti-CD20, and JAK inhibitors) Methotrexate is a folate antagonist which should be co-prescribed with folic acid because it is teratogenic. Once weekly dosing should be used as oral or subcutaneous. There needs to be regular monitoring with FBC, U&Es and LFTs. Methotrexate does not cause pulmonary fibrosis but can cause acute pneumonitis. Be aware of other folate antagonists such as trimethoprim which should never be co-prescribed. Targeted therapy is used after 2 failed DMARDs. Steroid treatment increases the risk of osteoporosis and patients with RA are twice as likely to have cardiovascular disease so should be encouraged to stop smoking, monitor cholesterol, and give lifestyle advice. RA has an increased risk of infection due to the immunosuppressive drugs or poorly controlled RA. Serious unusual infections such as pneumocystis and mycobacterium should be checked for.

Answer 46

Rheumatoid nodules: Firm lumps that develop under the skin, often around joints or pressure points, such as the elbows or heels. Vasculitis: Inflammation of blood vessels that can cause skin rashes, ulcers, or nerve damage. Interstitial lung disease: Inflammation and scarring of the lungs that can lead to shortness of breath, coughing, and chest pain. Sjögren's syndrome: An autoimmune disorder that affects the salivary and tear glands, leading to dry eyes and mouth. Felty's syndrome: A rare complication of RA that involves an enlarged spleen and a low white blood cell count. Pericarditis: Inflammation of the lining surrounding the heart, which can cause chest pain and shortness of breath. Ocular inflammation: Inflammation of the eyes that can lead to redness, pain, and vision problems. Anemia: A deficiency of red blood cells, which can cause fatigue, weakness, and shortness of breath. Neuropathy: Damage to the nerves that can cause numbness, tingling, or weakness in the hands and feet.

Answer 47

- Deformity and resulting disability - Osteoporosis can be directly associated with RA or from steroid use - Cardiovascular disease (2X risk) - Infection can be directly associated with disease or treatment affect

Answer 48

Axial: Ankylosing spondylitis Peripheral: Psoriatic, reactive, enteropathic, and seronegative (undifferentiated)

Answer 49

Psoriatic arthritis is much less common than RA and affects 13.8% of people with skin psoriasis. You do not need psoriasis to have the arthritis as some will have arthritis first and others only have a family history. Can present at any age but usually later in life and is just as likely in males and female. The initial presentation is more subtle than RA so there is often a diagnostic delay. Psoriasis can cause nail disease which often co-exists with arthritis as the nailbeds are close to the DIPs. The clinical presentation of PA includes axial spondyloarthropathy (affecting the enthesitis such as Achilles tendonitis), DIP joint disease, asymmetrical large joint oligoarthritic (persistent one knee and one ankle with no other joints) and rheumatoid-like small joint disease (Dactylitis which is severe inflammation of the whole tendon sheath causing sausage like deformity). Investigations: Same as RA but results will differ as there will be normal inflammatory markers. Radiographical findings include a pencil in cup formation which is known as arthritis metalans. This is rare due to improved treatment. Management: Holistic, MDT and patient centred. This should be managed with dermatology and disease monitoring is harder than in RA due to lack of inflammatory markers. Pharmacology: NSAIDs, then Steorids, then DMARDs (including Apremalist), then biologics (anti-TNF, JAK inhibitors, and AntiIL 17/23) Differences from RA include caution with systemic steroids as this can worsen the skin disease and cause pustular psoriasis which is severe. Combination therapy is not as effective as monotherapy. Two attempts with DMARDs progresses to targeted therapies which are different from the targeted therapies in RA.

Answer 50

Axial Spondyloarthropathy: Prevalence is lower than RA (1.4%) and varies with HLA B27 prevalence. The typical demographic is young men with a 3:1 ratio to women. The genetic association is very strong but no other known risk factors. Diagnosis should be confirmed with an MRI of the spine and Sacro-iliac joints, HLA B27 gene test and plain X-rays of the sacro-iliac joints. Diagnostic criteria: Modified New York Criteria: Clinical criteria: low back pain >3 months which is improved by exercise, limitation of the lumbar spine in sagittal and frontal planes, and limitation of chest expansion. Radiological criteria: Bilateral grade 2-4 sacroiliitis or unilateral 3-4 sacroiliitis ASAS criteria: Sacroilitis on imaging AND at least 1 SpA feature OR HLAB27+ AND 2 SpA features. Features can include inflammatory back pain, arthritis, enthesitis, uveitis, dactylitis, psoriasis, IBD, good response to NSAIDs, and a FHx of SpA Other investigations include FBC, U&Es, LFTs, CRP, ESR, HLA B27 and imaging. Management is with physiotherapy, and pharmacotherapy to aid working and physiotherapy engagement. There is minimal evidence for any disease-modifying treatment. Steroids are not a long-term treatment option. Pharmacology: NSAIDs (naproxen or Etoricoxib), then consider Steroids for single joint injections, then DMARDs (only for peripheral jont disease), then biologics (anti-TNF and AntiIL 17/23). Associations include (5As) Apical pulmonary fibrosis, Aortic regurgitation, AV block, Anterior uveitis, and Achilles tendonitis. There is also an association with extrinsic lung restriction, functional impairment, mental health issues and osteoporosis.

Answer 51

Hot joint means an acutely swollen, tender joint which is typically a monoarthritis and causes restricted range of motion. It may look erythematous, and the patient may be systemically unwell. Septic arthritis is a medical emergency. Acutely hot joint should be considered septic until proven otherwise.

Answer 52

Alcohol is a risk factor for gout and sexual history is a risk factor for gonococcal arthritis. Risk factors for septic arthritis include: - Immunosuppression/diabetes/alcohol excess - Damaged joints from RA/OA/Joint replacements - Opportunistic infections through a skin wound/IVDU or IA steroid injection

Answer 53

Investigations: 1. Synovial fluid aspiration – WCC over 100,000 indicates sepsis, under 50,000 is unlikely. If pus is aspirated, it is very likely sepsis. The aspirate will also be gram stained and investigated by microbiology (only 80% of septic arthritis grows something so blood cultures vital). 2. Bloods: CRP, ESR, FBC, LFT, U&Es, urate and consider CCP/RF 3. Blood cultures 4. X ray 5. Urinalysis 6. Consider MRI/USS (hip joint) 7. Consider genital swabs Never aspirate a prosthetic joint due to risk of infection. This should be done by Ortho.

Answer 54

Differentials: - Septic arthritis - Crystal arthritis - Inflammatory arthritis - Trauma - Haemarthrosis (clotting disorder such as sickle cell or trauma history)

Answer 55

The Kocher criteria for septic arthritis Fever (38.5), ESR (>40), WCC (>12), and non-weight bearing. One point for each. 1: 3% chance of septic arthritis 2: 40% 3: 93% 4: 99%

Answer 56

Management of septic arthritis is with aspiration, IV Abx (typically flucloxacillin 2g QDS as most is caused by staphy aureus) and referral to Ortho/Rheum depending on local pathway. If Gonorrhoea, then treat with ceftriaxone or cefuroxime. Mortality is 10% with complications including irreversible joint damage, sepsis and osteomyelitis.

Answer 57

This affects 2% of the populations and is caused by uric acid crystals forming in and around the joint. Patients have a raised urate and negatively birefringent needles under polarised light. “Podagra” describes a gout attack in the big toe. Repeat attacks on a joint will cause joint destruction and tophi. Risk factors for gout include alcohol, CKD, medication (diuretics), genetics, high purine diet and metabolic syndromes/HTN.

Answer 58

Treatment of acute gout: 1. Colchicine 500mg BD or TDS and can be taken up to QDS but may cause diarrhoea. It should be avoided in an eGFR less than ten and used with caution in liver disease. It is typically taken until the symptoms have settled or up to 5 days. Interactions include cyclosporine, macrolides and verapamil. There is an increased risk of myopathy with statins co-prescribed. 2. NSAIDs – should be used with caution if there has been a previous GI or bleed or the patient is elderly. Consider a PPI in addition. 3. Prednisolone can be given PO, IM or IA and consider a PPI. Should only be used if other treatments cannot be given. 20-30mg once a day for a week PO.

Answer 59

Lower the urate levels as this will reduce or stop the patient having flares. This can be achieved through patient education, lifestyle advice (cherries, smoking and alcohol), weight loss, treating underlying CVD risk factors, allopurinol, and febuxostat. Prophylactic medication include colchicine/pred/NSAIDs). Urate lowering therapies can be considered where the diagnosis of gout is made and there are gouty tophi, renal impairment, joint damage or 2 flares in a 12-month period. Some patients initiate treatment after their first attack. Allopurinol is a xanthine-oxidase inhibitor and is used first line. It is started low at 50-100mg once daily and increased every 4 weeks by 100mg until the target urate level is reached which is less than 300 micromoles per litre. LFTs and U&Es are checked with urate every 4 weeks. The maximum dose of allopurinol is 900mg and most patients require 400mg to reach their target. Allopurinol can cause Stephen Johnson’s syndrome or DRESS syndrome (Hypersensitivity drug reactions with rash eosinophilia and systemic symptoms). It should be used in caution in patients with HLA group v5801 which is common in Korean/Han Chinese/Thai people. Febuxostat is used second line or for patients who cannot have or tolerate allopurinol. It is started at 80mg once daily and increased to 120mg once daily after 4 weeks if needed. It should not be used in patients with IHD or HF. If neither of these xanthine-oxidase inhibitors can be used then rheumatologists may prescribe benzbromarone. Urate lowering medications should not be started until at least 2-4 weeks after an acute flare. If allopurinol or febuxostat is initiated then a prophylactic medication should also be given such as colchicine 500mg daily for 6 months.

Answer 60

Pseudogout is calcium pyrophosphate dihydrate crystal deposition and it most commonly affects the knees and wrists. Urate will be normal. X-ray may show chondrocalcinosis which classically appears as rhombus shaped crystals. These crystals are positively birefringent under polarised light, unlike gout. Acute treatment is the same as gout with colchicine, NSAIDs or prednisolone. Chronic pseudogout should be referred to rheumatology as there are no proven treatments but DMARDs or long term low dose colchicine may be used.

Answer 61

Stroke is the 3rd most common cause of death and accounts for 11% of all deaths. It is also the main cause of preventable disability and it is treatable. Stroke is defined as the sudden onset of a focal neurological deficit, lasting more than 24 hours (or leading to death) due to either infarction (85%) or haemorrhage (15%). A TIA is a neurological deficit lasting less than 24 hours.

Answer 62

The MRC scale is used for testing power in a neurological examination: 5- Normal power 4- Active movement against gravity with resistance 3- Active movement against gravity without resistance 2- Active movement with gravity eliminated 1- Flicker of movement 0- No movement

Answer 63

Modified Rankin scale (mRS) is used to measure disability/dependence in people who have suffered a stroke or other causes of neurological disability. 0: No symptoms 1: no significant disability. Able to carry out usual activities, despite some symptoms 2: Slight disability. Able to look after own affairs without assistance, but unable to carry out previous activities 3: Moderate disability. Requires some help, but able to walk unassisted 4: Moderately severe disability. Unable to attend to own bodily needs without assistance and unable to walk unassisted. 5: Severe disability: Requires constant nursing care and attention, bedridden and incontinent 6: Dead

Answer 64

Total anterior circulation stroke (TACS): Symptoms are hemiparesis +/- hemisensory loss AND homonymous hemianopia AND cortical dysfunction (dysphasia/perceptual problem). TACS are caused by MCA infarcts. There is a 40% chance of death in 30 days and 60% dead in a year. Worst stroke to have.

Answer 65

Partial Anterior Circulation Stroke (PACS) will have 2/3 of the TACS criteria: Hemiparesis +/- hemisensory loss, homonymous hemianopia, AND/OR cortical dysfunction (dysphasia/perceptual problem). PACS should also be considered in cortical dysfunction alone. This is a partial occlusion of the MCA.

Answer 66

Lacunar Stroke (LACS) presents with hemiparesis OR hemisensory loss OR hemisensorymotor loss OR ataxic hemiparesis. There is no cortical dysfunction or hemianopia.

Answer 67

Posterior Circulation Stroke (POCS) presents with brainstem nuclei or cerebellar signs and symptoms, there can also be occipital signs. Therefore symptoms can include diplopia, vertigo, ataxia, bilateral limb problems, hemianopia and cortical blindness. There is a 7% chance of death in 30 days and 20% in 1 year.

Answer 68

This is a scale used by non-specialist trained clinicians in ED for stroke. First check glucose and treat if low. Then a score greater than 0 (1-6) indicates an acute stroke is likely, a score of 0 or below means stroke is unlikely.

Answer 69

The ischaemic core (irreversible damage) occurs in the area of brain tissue local to the blood vessel occlusion whose blood supply is entirely supplied by this vessel and so it dies. The ischaemic penumbra (salvageable tissue) is the area surrounding the ischaemic core with some collateral blood supply, but blood supply has been reduced by the infarct. Without intervention much of this area will also die. Over subsequent hours this area will either become viable again or join the ischaemic core. Acute investigations and management should include a CT brain, bloods, ECG, CXR, Aspirin 300mg APAP if no bleed on the scan and Stroke Unit MDT care. The Stroke Unit employs careful monitoring and correction of physiological parameters such as hypoxia, glucose, BP, and pyrexia. There should be early SALT input, feeding, physiotherapy, rehab, and psychological input. The earlier the treatment the better the outcomes as the penumbra is likely to be larger. As the penumbra disappears, stroke therapy such as thrombolysis becomes ineffective. Most patients no longer have a penumbra after 4.5 hours which means the risk of bleeding is higher and usually outweighs the benefits of thrombolysis.

Answer 70

Thrombolysis is with IV Alteplase. A bolus of 10% of total dose (0.9mg/kg) is then followed by an infusion of the remaining 90% over 1 hour. This should be given within 4.5 hours of the onset of symptoms. An urgent CT brain is required to exclude a bleed prior to treatment. With early treatment the mRS score is more likely to be under 2. Complications of thrombolysis include bleeding and angioedema. A repeat CT brain should be done at 24 hours.

Answer 71

Contraindications of thrombolysis include intra-cranial haemorrhage, neurosurgery/stroke within 3 months, uncontrolled HTN, active internal bleeding, endocarditis, known AVM, impaired coagulation, anticoagulant use, and significant hypoglycaemia.

Answer 72

Thrombectomy is mechanical clot retrieval which is offered up to 6 hours post symptom onset. This is usually used second line after failed thrombolysis. There are favourable outcomes with mRS score under 2 after 90 days in 40%. Risk of serious complications include intracranial haemorrhage, access site complications, vessel perforation and distal emboli.

Answer 73

Secondary prevention is with clopidogrel 75mg OD after 2 weeks of Aspirin 300mg OD. The cholesterol target is under 4 and a statin can be added if required. Target BP is under 130/80 and diabetes should be screened for and treated. Smoking cessation, screen and treat carotid stenosis, screen and treat AF, order an ECHO and discuss driving restrictions.

Answer 74

Stroke complications include aspiration pneumonia, intracerebral haemorrhage with surrounding oedema and midline shift, malignancy MCA syndrome, and hemicraniectomy.

Answer 75

These are strokes which last less than 24 hours and should be considered a warning sign of an impending stroke. The ABCD2 score for TIA can be used to assess stroke risk but an suspected TIA should be treated with 300mg Aspirin OD and referral to TIA clinic within 24 hours. They will organise an Doppler, ECG, Echo, 24 hour ECG and MRI.

Answer 76

Presentation within 4.5 hours of onset means there is salvageable brain tissue which is being threatened. There is no bleed on the CT. Therefore, thrombolysis is indicated.

Answer 77

The medical definition of a fall is inadvertently coming to rest on the ground, floor, or other lower level, excluding an intentional change in position to rest in furniture, wall or other objects. The most at-risk age groups from falls are under 5s, younger adults in dangerous circumstances and the over 65s. This is a symptom and not a diagnosis and was known as one of the geriatric giants. The Geriatric giants are Immobility, Incontinence, Impaired cognition (confusion) and Instability (falls). Over 50% of hospitalisations in the over 65s are related to falls. Severe and life-threatening injuries include spinal fractures, NOF, and brain injury. Patients often experience a post falls syndrome where there is a fear of falls and thus a negative feedback spiral. Falls risk reduction is possible if actions are taken. Falls and balance is related to interactions of multiple factors include visual/sensory input, proprioception, MSK, vestibular, cerebellar, cerebral/neurological, haemodynamic and environmental.

Answer 78

When assessing a falls history it should include pre-fall, peri fall, and post fall including injuries. Previous falls, PMH, medication, social, environmental and facture risk are very important considerations. If a patient says ‘I must have tripped’ it means they did not trip. Brief LOC may not be mentioned without direct questioning and “went over” usually implies a balance problem. When a patient mentions dizziness you should clarify pre-syncope, vertigo or disequilibrium. A falls assessment examination should include GAIT, CVS, Neurological, cognitive, MSK, vision, vestibular and psychological. Investigations should include bloods FBC, BMs, B12, Vitamin D and TFTs, ECG, cardiac monitoring, tilt table and brain imaging but this depends on the history and examination. A fall in an older person can never be described as a simple fall and should not be described as mechanical either. Falls risk is increased in older age (especially over 85s), previous fall history, cognitive impairment, visual impairment, polypharmacy, functional impairment, orthostatic hypotension and a PMH of PD, dementia, OA, DM II or stroke.

Answer 79

Orthostatic hypotension is a sustained reduction in systolic blood pressure of at least 20mmHg or diastolic BP of 10mmHg within three minutes of standing or tilting the body to a 60 degree angle. It is often iatrogenic from antihypertensives or diuretics. Treatment is to modify these medications, keep hydrated, compression stockings, increased salt intake and consider medications of Fludrocortisone. Essentially treatment for falls is risk reduction. Contributory mechanisms should be identified and altered. The most amenable are haemodynamic issues, medication, cataracts, environment, strength training, vitamin D and education. This does not eliminate the risk of falls but mitigates it.

Answer 80

This should be screened for in all women 65+ and all men 75+. It should also be screened for in women 50+ or men 50+ if they have any of the following risk factors of previous fragility fracture, current or frequent use of steroids, history of falls, low BMI, smoker, excess alcohol intake or secondary cause of osteoporosis. Bone health assessment is performed with a DEXA scan but drug treatment can be offered to patients vertebral or hip fractures without having a DEXA scan. All other people with risk factors for Osteoporosis should have a 10-year fragility fracture score calculated prior to arranging a DEXA. Other potential causes of fragility fractures include metastatic bone disease, multiple myeloma, osteomalacia and Paget’s disease. Vitamin D deficiency should be assessed as it is very common in 65+ and a calcium intake of at least 1000mg/day is recommended for people at increased risk of fragility fracture. Secondary causes of osteoporosis include endocrine conditions (premature menopause, T2 DM, hyperthyroidism and hypogonadism in men), rheumatological conditions (RA or other inflammatory arthropathies), GI conditions (Crohn’s, UC, coeliac and chronic pancreatitis), chronic liver disease and COPD.

Answer 81

Delirium is an acute medical condition manifesting as psychiatric illness. It is an acute medical emergency. It is acute, reversible confusion, related to a medical cause. Key features are acute cognitive impairment, fluctuation in time, affected attention and alertness (hyperactive, hypoactive or mixed). Risk factors include cognitive impairment, previous delirium, frailty, increasing age, severe illness, polypharmacy, sensory impairment, multiple long term health conditions and dependence on alcohol or opiates. Delirium can be identified by 10/4 AMT, MMSE, MOCA, 6-CIT or other tools. The 4AT is the most common tool. This should be used to identify early in illness as hypoactive delirium is often missed. If there are no current signs of delirium but the patient is high risk then preventative strategies should be used when planning treatment.

Answer 82

Prevention is with keeping familiar staff around the patient, avoid room changes, lighting, signage, frequent re-oreintation, family and friends, hydration, optimise oxygen, treat infection, avoid medical equipment such as catheters or lines, encourage mobility, manage pain, review medication, encourage nutritional intake, hearing and visual aids and promote good sleep hygiene.

Answer 83

If delirium is present the underlying cause needs to be identified and treated. Preventative measures are still important and even if resolution of cause the delirium can persist for weeks to months.

Answer 84

P - Pain I - Infection N – Nutritional compromise C - Constipation H - Hydration M – Medication E – Environmental

Answer 85

There should be verbal and non-verbal de-escalation with a medication review to look for contributing factors. Benzodiaepines should be avoided as they prolong delirium. Antipsychotics may be useful but it is debatable, NICE Recommend Haloperidol 0.5mg, except in PD or LBD which may need a low dose benzodiazepine.

Answer 86

Patients must be able to understand information given to them, retain that information for long enough to make a decision, weigh up information available to make a decision and communicate their decision. If a patient is unable to make a decision then a decision must be taken in the patient’s best interest. Check the advance directive and discuss with POA. A relative can acts as an advocate.

Answer 87

Deprivation of Liberty Safeguard (DoLS) is a safeguard for a person whose freedom is restricted In some way. There should be scrutiny of this decision to guard against inappropriate restrictions.

Answer 88

Any patient with 24 hour protein more than 1g or PCR:ACR more than 100:70 then a renal biopsy is needed. Lower than these levels but evidence of significant renal disease should also have a renal biopsy.

Answer 89

The three main complications of nephrotic syndrome are infection, hypercoagulable state and hyperlipidaemia.

Answer 90

This is a nephrotic syndrome because there is heavy proteinuria (>3.5g/24hrs), hypoalbuminemia (<30g/L) and significant peripheral oedema. Hyperlipidaemia and thrombotic disease are also common.

Answer 91

This now requires a nephrology referral and kidney biopsy to assess the cause of the nephrotic syndrome

Answer 92

Minimal change disease accounts for 90% of nephrotic syndromes in children <10. In adults it is largely idiopathic or caused by NSAIDs/Hodgkin’s lymphoma. In MCD the injury affects the podocytes but in light microscopy there is little inflammation or cell proliferation in the glomerulus. On electron microscopy there will be diffuse effacement of the epithelial cell foot processes. The clinical triad of MCD, NS and AKI has been described post influenza/COVID-19 vaccinations.

Answer 93

The most common cause in children is minimal change disease. In adult men the most common cause is primary glomerular diseases whereas in women secondary disease is more likely (diabetes, amyloidosis, or SLE). The most common cause in younger adults is focal segmental glomerular sclerosis (FSGS) followed by minimal change nephropathy. Membranous nephropathy is the most common cause in older people and diabetic nephropathy in those with a history of diabetes. Nephrotic syndrome can develop in patients with IgA nephropathy, membranoproliferative glomerulonephritis, and post-infectious glomerulonephritis but these are usually nephritic with haematuria and red cell casts as the predominant feature.

Answer 94

Nephritic syndrome is characterised by the presence of haematuria frequently in association with HTN, oliguria, fluid retention and usually reduced renal function. Patients may exhibit varying degrees of proteinuria including nephrotic range but the prominence of haematuria on the dipstick indicates glomerulonephritis. Urine analysis will show the pattern of glomerular injury and with the clinical picture provide the diagnosis. Damage to the podocytes causes heavy proteinuria whilst glomerular injury caused by autoantibodies or immune complex deposition usually causes haematuria +/- mild to moderate proteinuria.

Answer 95

Treat the underlying cause of the nephrotic syndrome. Symptomatic improvement should be achieved through dietary sodium restriction and a loop diuretic (furosemide/bumetanide). Normal protein intake is advisable. A high-protein diet will increase the proteinuria which can be dangerous long term. Lipid abnormalities in patients with longstanding NS and non-responsive to treatment should be addressed with a statin. ACE inhibitors/A2RB are indicated for their antiproteinuric properties in all types of glomerulonephropathy and especially in the nephrotic syndromes. There is a hypercoagulable state which predisposes people to VTE. Prolonged bed rest should be avoided and LMWH should be considered. Patients with long-standing NS are at higher risk of infection due to loss of immunoglobulins in the urine. Pneumococcal infections are particularly common so the vaccine should be offered. Early detection and aggressive treatment of infections is preferable to prophylactic antibiotics. Many primary glomerular diseases require immune suppressive treatment. First line, high dose corticosteroids, then calcineurin inhibitors (ciclosporin or tacrolimus). Alternatively, cyclophosphamide or chlorambucil can be used. Occasionally mycophenolate Mofetil or Azathioprine are tried. Rituximab is the biologic which is rarely used, it attack the CD20.

Answer 96

Investigations should include inflammatory markers (FBC, ESR and CRP), renal profile (CKD risk factor for crystal arthropathies and AKI may be sepsis related), clotting (hemarthrosis), serum uric acid and plain X-ray (trauma/ chondrocalcinosis seen in calcium pyrophosphate deposition). Blood cultures and joint aspiration is the GOLD standard test and may need USS guidance. Joint fluid should be examined for cell count (>50,000 suggests sepsis), differential cell count (predominantly neutrophils present in bacterial joint infections), gram stain, culture, sensitivities, and polarised light microscopy looking for crystals.

Answer 97

‘Gram positive cocci in clusters’ is a typical description of S Aureus which is likely to have been introduced by the direct inoculation at the time of steroid injection. S aureus is a skin commensal therefore it is introduced like this. It can also be due to haematogenous spread due to IVDU or endocarditis. Secondary infection from neighbouring tissue is seen in osteomyelitis and septic bursitis. Other causative organisms can include coagulase negative Staphylococci (prosthetic joints), E coli, Neisseria gonorrhoeae, TB, Lyme disease, and very rarely fungal infections. Synovitis can be caused by viruses such as parvovirus B19, Rubella and Alphaviruses (chikungunya). These do not cause sepsis.

Answer 98

Management can be conservative (rest, splinting, analgesia, stop immunosuppressives, and physio), medical (supportive fluid therapy and antibiotics), or surgical (washout to control the infection as the synovium is so vascular that this behaves like an abscess and antibiotics penetrate poorly).

Answer 99

Flare of RA due to the pause in immunosuppression. Systemic infection can precipitate flares as well as vaccination and childbirth. Flare can be short-lived or become persistent. This should be managed with steroids, or high dose NSAID and analgesia to avoid steroids.

Answer 100

Sodium chloride 0.9% 500ml IV over 15 minutes because NICE guidance says that a crystalloid should be used with a sodium content in the range of 130-154mmol/L with a bolus of 500ml over less than 15mins. Suitable options include sodium chloride 0.9%, Hartmann’s or Ringers Lactate. If 500ml of Hartmann’s is infused IV over 10 mins then the correct infusion rate is 3000ml/hr to make it 500ml in 10 mins. IV fluid resuscitation should be given as 250ml sodium chloride 0.9% bolus over 15 mins if the patient is at risk of fluid overload. For patient who do not respond to 500ml fluid bolus then an IV bolus can be repeated up to a maximum of 2 litres. Patients should be reassessed after 15mins and a repeat bolus can be given if any of the following still apply: Systolic <100, HR >90, cap refill >2s, RR >20, NEWS >4- or 45-degree passive leg raise suggests fluid responsiveness. If there is no response after 2 litres then the diagnosis should be questioned and expert help sought. Glucose is not appropriate for fluid resuscitation because it disperses rapidly across all fluid compartments so is considered ‘free water.’ Resuscitation is monitored by observations are returning to normal.

Answer 101

For routine maintenance the patient requires 50-100g of glucose per day and 70mmol of chloride per day because they are 74 kg. NICE guidelines state that normal fluid and electrolyte requirements of an adult is 25-30ml/kg/day of water, 1mmol/kg/day sodium/potassium/chloride, and 50-100g/day glucose (glucose 5% contains glucose 5g/100ml). Patients who are frail, malnourished, renal impairment or heart failure should be prescribed less at 20-25ml/kg/day. In obese patients the prescription should be based on ideal body weight and the lower range volumes per kg used.

Answer 102

Cockcroft-Gault equation. This can be used to determine whether a patient is in AKI. This includes sex, age, weight, height, and creatinine. Serum creatinine can only be used to estimate GFR in individuals with stable kidney function. Early in AKI the GFR is markedly reduced but the creatinine is yet to accumulate and thus serum creatinine does not reflect the renal dysfunction.

Answer 103

Morphine should be switched to modified release oxycodone and switch morphine sulphate 10mg/5mL oral solution for breakthrough pain to oxycodone immediate-release liquid. Oxycodone does not create any active metabolites which can cause prolonged action like morphine in renal impairment.

Answer 104

Nitrofurantoin is contra-indicated with a CrCL less than 45 mL/min because antibacterial efficacy depends on renal secretion of the drug into the urinary tract where it acts locally. Trimethoprim can be used by requires 50% reduction in dose after 3 days. Male so 7-day course needed. 200mg BD for three days and then 100mg BD for 4 days. A stat dose should be prescribed on the once one prescription chart so the first dose is not delayed.

Answer 105

This advice is because NSAIDs and anti-hypertensives impair renal autoregulation increasing the risk of AKI. Further some drugs may accumulate as a result of reduced kidney function in AKI, increasing the risk of adverse effects such as metformin (lactic acidosis), sulphonylureas (hypoglycaemia), and trimethoprim (hyperkalaemia).

Answer 106

This encompasses all patients over the age of 65. Common presentations include UTI, LRTI, constipation, incontinence, dizziness, mobility issues, cognitive impairment, delirium, T2DM, COPD, OA, osteoporosis, loneliness, self-care issues, and complications of polypharmacy.

Answer 107

It is a state of vulnerability to poor resolution of homeostasis after a stressor event and is a consequence of cumulative decline in many physiological systems during a lifetime. This affects 10% of over 65s and 50% of over 80s.

Answer 108

This is a model for understanding domains which can interact to alter the balance between resilience and vulnerability for frail elderly patients. The domains include: Social environment, physical environment, psychological status, long term conditions, acute health problems, and systems of care.

Answer 109

Falls, immobility, delirium, incontinence, and susceptibility to side effects of medication.

Answer 110

There are a variety of frameworks including the PRISMA 7, Edmonton Frailty Scale, and Rockwood Frailty Score.

Answer 111

GOLD standard is comprehensive geriatric assessment with MDT assessment of physical issues, function, environment, mobility, balance, psychosocial issues and medication. Exercise interventions include core strength, flexibility, balance, and endurance training. Nutrition support is with considerations of total protein intake, calcium and vitamin D. Raised BMI is associated with poor outcomes. There should be a medication review and advance care planning.

Answer 112

1. Anticholinergics: Unsteadiness, blurred vision, dry mouth, urinary retention, and confusion 2. Benzodiazepines: Falls, increased all cause mortality, and confusion 3. Opioids: Constipation, falls, and delirium 4. NSAIDs: AKI and gastric ulceration 5. Antihypertensives: AKI and falls

Answer 113

Risk 1: Haloperidol, Quetiapine, Mirtazapine, paroxetine, trazodone, and ranitidine Risk 2: Clozapine, Nortryptyline, baclofen, certirizine, loradatine, cimetidine, loperamide, prochlorperazine, and tolterodine RIsk 3: Chlorpromazine, amytrypyline, Imipramine, Chlorpheniramine, Hydroxyzine, and Oxybutinin

Answer 114

This is the number 1 reason for ED attendance in older adults. The 1 year mortality following a hip fracture is 33% and a further 20% will enter a care home within 12 months. It should always be investigated why a patient has fallen. Causes of falls are subdivided into categories including motor problems, sensory impairment, polypharmacy, cognitive/mood impairment, co-morbidities, environmental hazards, orthostatic hypotension, and frailty. Patients should be assessed by their GP for falls risk and referred to the falls prevention service with physio, OT, and geriatrician MDT.

Answer 115

Delirium: An acute confusional state (hours/days) which often fluctuates over the course of an illness. It is generally reversible and can present with altered consciousness. Causes include infection, medication, and environmental change. Dementia: An insidious, chronic decline in cognition and function (months to years) which is slowly progressive. It is irreversible and the patient is generally alert. It is caused by Alzheimer’s disease, vascular disease, lewy bodies or others.

Answer 116

Features of inflammatory joint pain: This can affect any joint, stiffness lasts for longer than 30 minutes, the progression was rapid, can occur at any age, are treated with immunosuppressants, and risk factors include smoking/hormones/genetics/obesity. Features of mechanical joint pain: Typically involves hands/spine/knees/hips, stiffness lasts less than 30 minutes, condition had a gradual onset, occurs in the over 45s, treated with analgesia/PT/joint replacement, and risk factors include age/genetics/fractures/obesity.

Answer 117

- Arthralgia: Joint pain - Myalgia: Pain in muscles - Arthritis: Joint inflammation - Myositis: Muscle inflammation - Synovitis: Inflammation of a synovial membrane

Answer 118

OA hand deformities: Squaring of the thumb base, Bouchard’s nodes (PIP), and Heberden’s (DIP) nodes. RA hand deformities: Swan neck deformity and boutonniere deformity

Answer 119

Rheumatoid arthritis affects the small joints and presents with swelling, stiffness, symmetrical patter and can present with systemic features.

Answer 120

Ankylosing spondylitis (AS) is a chronic inflammatory disease that primarily affects the spine and sacroiliac joints (the joints connecting the spine to the pelvis). It belongs to a group of conditions known as spondyloarthropathies, which involve inflammation of the joints and ligaments. The hallmark feature of ankylosing spondylitis is the inflammation and fusion of the vertebrae in the spine, leading to stiffness and limited mobility. Over time, the inflammation can also affect other joints, such as the hips, shoulders, and knees. In some cases, other areas of the body, such as the eyes, heart, and lungs, may also be involved.

Answer 121

There is a 30% association with psoriasis rash and typically presents as oligoarthritis (2-4 joints). There may be dactylitis and enthesitis.

Answer 122

This is a response to an infective trigger and is associated with HLA B27. Reiter's syndrome is a form of arthritis that causes oligoarthritis, urethritis, and conjunctivitis.

Answer 123

This is a type of arthritis associated with inflammatory bowel disease. The condition causes joint inflammation and tenderness in the arms, legs and sometimes spine. It also involves digestive problems.

Answer 124

Mechanical joint pain of large joints, DIPS and CMCs. It can be monoarticular or polyarticular. There will not be any systemic involvement and normal inflammatory markers.

Answer 125

This presents with a hot swollen joint and is almost always monoarthritis. They will be systemically unwell with raised WCC/CRP. Risk factors are immunocompromise, IA injection, damaged joints, and open wounds. 80% are caused by staphylococcus aureus.

Answer 126

This typically presents in the 1st MTPJ and has a hyperacute onset. There will be raised uric acid, negatively birefringent under polarised light and it is association with renal failure, alcohol and drugs (diuretics).

Answer 127

This presents with a variety of symptoms, raised ESR/CRP, and can be ANCA associated. Common examples are GCA and PMR and vasculitis can be categorised as large/medium/small vessel.

Answer 128

This presents with rashes and Raynaud’s with systemic features. Antibodies associated with connective tissue diseases include ANA, RO, LA, DsDNA, Centromere, and SCL-70.

Answer 129

Widespread chronic pain, unrefreshing sleep, low mood, paraesthesia, memory loss and headaches. This is treated with antidepressants and CBT.

Answer 130

Immobility, instability (postural), impaired cognition, and incontinence.

Answer 131

Excessive accumulation of fluid within the interstitial space. This is detected by the persistence of an indentation in the tissue following pressure (pitting oedema). Pitting oedema tends to accumulate in ankles during the day and improves at night as the interstitial fluid is reabsorbed. Non-pitting oedema is typical of lymphatic obstruction and may occur as the result of excessive matrix deposition in tissues such as hypothyroidism or systemic sclerosis. Pulmonary oedema: This has a Bat’s wing or butterfly appearance of pulmonary opacities on X-ray due to bilaterally perihilar shadowing. This can present with Kerley B lines and pleural effusions.

Answer 132

Poor skin turgor, dry mucus membranes, thirst, yellow and strong smelling urine, dizziness, fatigue, tachycardia and poor urine output.

Answer 133

This is defined as a decline in kidney function over 48 hours demonstrated by serum creatinine rises by over 26 umol/L, serum creatinine rises above 1.5 from baseline and urine output less than 0.5ml/kg/hr for over 6 hours. This results in failure to maintain fluid, electrolyte and acid-base homeostasis. Grade 1: 1.5-1.9 times baseline for over 0.3 (26.5 umol) increase and urine output less than 0.5ml/kg/hr Grade 2: 2.0-2.9 times baseline and less than 0.5ml/kg/hr of urine for more than 12 hours Grade 3: 3.0 times baseline or increased in serum creatinine of 353 umol/L or initiation of renal replacement therapy. Less than 0.3ml/kg/hr for more than 24 hours or anuria for more than 12 hours.

Answer 134

Pre-renal: Impaired perfusion so cardiac failure, sepsis, blood loss, dehydration, and vascular occlusion. Renal: Glomerulonephritis, small vessel vasculitis, acute tubular necrosis, drugs, toxins, prolonged HTN, and interstitial nephritis. Post-renal: Urinary calculi, retroperitoneal fibrosis, BPH, bladder cancer, prostate cancer, cervical cancer, urethral stricture and meatal stenosis.

Answer 135

Assess potassium, fluid volume status assessment, urine dipstick, medication review to stop nephrotoxic, image renal tract to exclude post renal causes and other investigations to consider are ANCE and myeloma screen.

Answer 136

1. >5.5 means repolarisation abnormalities such as peaked T waves 2. >6.5 means progressive paralysis of the atria with P wave flattening and PR prolongation 3. >7 means conduction abnormalities and cardiac arrest so will have wide QRS, AV conduction blocks, sine wave, asystole, VF and PEA.

Answer 137

Indications are refractory hyperkalaemia, refractory pulmonary oedema, progressive severe metabolic acidosis (pH <7.2, HCO3- <10) and symptomatic uraemia such as pericarditis or encephalopathy.

Answer 138

This is diagnosed when there is evidence for more than 3 months of kidney damage (urine albumin >30 mg/g creatinine, haematuria, or parenchymal abnormalities) or decreased kidney function (GFR <60 ml/min). Causes include diabetes, HTN, chronic glomerulonephritis, failed transplant, polycystic kidney disease, interstitial nephritis, obstructive nephropathies, vascular disease and autoimmune diseases. Complications include fluid overload, HTN, hyperkalaemia, acidosis, anaemia, uraemic syndrome, mineral bone disease and cardiovascular risk.

Answer 139

Haemodialysis: Removal of certain elements from the blood while it is being circulated and exposed to dialysate across a semi-permeable membrane. The concentration difference across the membrane allows molecules to diffuse down the diffusion gradient which allows waste products to be removed. Patient require vascular access. Hemofiltration: Convection of water with solute drag across membrane and replacement with fluid balanced solution. Peritoneal dialysis: Solute and fluid exchange occur between peritoneal capillary blood and dialysis solution in the peritoneal cavity which is usually done at home. Transplant is done when kidneys are available for suitable candidates. Requires life-long immunosuppression.

Answer 140

All transplant patients have CKD, are at risk of AKI, are immunosuppressed and have the potential for non-renal disease. Therefore, patient should be assessed in the same way and not assume they have a renal complication. Acute rejection is most common in the first year and most AKIs after the first year are not a symptom of rejection. Acute rejection presents with AKI. Most patients will be taking a calcineurin inhibitor such as tacrolimus or ciclosporin which can interact with cimetidine, erythromycin, St John’s wart and many others. Immunosuppression increases the risk of infection, including atypical organisms, and the risk is highest in the 1st year. EBV and CMV is much more common when the kidney donor was positive, and the recipient is negative. Atypical malignancies in immunosuppressed patients include post-transplant lymphoproliferative disease (lymphoma likely related to EBV) and skin malignancies such as SCCs. Sirolimus is an immunosuppressant which is associated with poor wound healing and so it should be stopped and an alternative used if the patient is scheduled for surgery.

Answer 141

- Normal: 135-145 mmol/L - Mild hyponatraemia 130-134 mmol/L - Moderate 125-129 mmol/L - Severe <125 mmol/L

Answer 142

Causes include medications, reduced blood volume, SIADH, renal salt wasting, primary polydipsia, Endocrine (Addison’s and hypothyroidism), and pseudohyponatremia. Symptoms: Nausea, vomiting, confusion, reduced GCS, headache and seizures.

Answer 143

Examination should include fluid status, signs of hypoaldosteronism, signs of thyroid dysfunction and urine output. Investigations: This should always include a urine and serum osmolarity, dipstick, U&Es, cortisol, TFTs, and blood glucose.

Answer 144

These can include thiazide diuretics (Bendroflumethiazide), loop diuretics (furosemide), potassium sparing diuretics (spironolactone), ARBs (Candesartan), tricyclic antidepressants (amitriptyline), SSRIs, MOA inhibitors (phenelzine), PPIs (omeprazole), AEDs (carbamazepine and valproate), and others such as Venlafaxine, Duloxetine, Chlorpropamide, Glimeripide, and Glipizide. SIADH results will be confounded by diuretics, hyperglycaemia and raised lipids.

Answer 145

Secondary care management of hyponatraemia is aimed at determining and treating the underlying cause. Management strategies depend on the rate of onset of hyponatraemia, the person's symptoms, and their volume status. * Acute hyponatraemia with moderate or severe symptoms: o Hypertonic saline restores serum sodium concentration to a safe level to correct any cerebral oedema and reduce the risk of complications. * Acute hyponatraemia with mild or no symptoms: o Non-essential parenteral fluids and medications that can provoke hyponatraemia are stopped and treatment is directed at the underlying cause. * Chronic hyponatraemia without moderate or severe symptoms: o Non-essential supplementary fluids and medications that can provoke hyponatraemia are stopped and treatment is directed at the underlying cause. * People with hypervolaemia: o Fluid and salt restriction is recommended to prevent further fluid overload. Consider diuretics * People with hypovolaemia: o Extracellular volume is restored with infusion of 0.9% saline or Hartmann’s. Amount of sodium replacement = 0.6 (which is total body water) x kg x 0.5(which is desired correction rate mmol/h). o Infusion rate = amount of sodium replacement (mmol/h) x (1000/154) * People with syndrome of inappropriate antidiuretic hormone secretion (SIADH): o Fluid restriction is recommended. If there is no clear cause for SIADH following initial investigations, CT chest/abdomen/pelvis and MRI head may be arranged to exclude underlying malignancy. o Tolvaptan (a vasopressin V2-receptor antagonist) is indicated in adults for the treatment of hyponatremia secondary to SIADH. Treatment should be initiated in hospital or under specialist supervision

Answer 146

Definition: 3+ RBC on microscopy (high power field) Glomerular causes: IgA nephropathy, vasculitis, isolated glomerulonephritis, Alport’s syndrome, polycystic kidney disease and thin membrane disease Non-glomerular causes: Infections, stones, trauma, malignancy, BPH, and gynae causes such as menstruation or endometriosis. IgA nephropathy usually presents with a history of URTI and an episode of frank haematuria. Vasculitis: They may have a history of rashes, epistaxis, haemoptysis, or joint pains. Alport’s syndrome is an inherited, usually X-linked, condition which causes IV collagen deficiency so insufficient basement membranes. They may also present with sensorineural deafness. Polycystic kidney disease and thin basement membrane has a strong family history.

Answer 147

Investigations should include urinalysis and microscopy for dysmorphic RBCs (passed through glomerulus), casts (immune or inflammatory) and nitrates. U&Es, FBC, CRP, ANCA, Anti-GBM, and PSA if appropriate. Imaging with is plain X-ray, USS and CT KUB (stones) or Urogram (malignancy). Extra tests are cystoscopy and renal biopsy.

Answer 148

Symptoms of ankylosing spondylitis typically develop gradually and vary among individuals. Common signs and symptoms include: Chronic pain and stiffness in the lower back and buttocks, which may worsen during periods of rest or inactivity. Limited range of motion in the spine, leading to a stooped posture. Pain and stiffness in other joints, such as the hips, shoulders, and knees. Fatigue and general discomfort. Inflammation of the eyes (uveitis) leading to redness, pain, and blurred vision. In some cases, involvement of other organs, such as the heart, lungs, or bowel.

Medicine C Flashcards

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