Medicine C Flashcards
What is frailty?
This is not about age but is more common in older people. It is often associated with being underweight, but this is also not true.
Frailty is defined as a physiological syndrome characterised by a decreased reserve and diminished resistance to stressors, resulting from cumulative decline across multiple physiological systems, and causing vulnerability to adverse outcomes.
What are the symptoms of frailty?
Symptoms of frailty can include mobility problems, falls, confusion, and incontinence. These can be caused by any illness such as respiratory tract infections. Frailty syndromes are not specific diseases and can present with a variety of symptoms. They can have any cause but are more likely with multiple impairments. Therefore, patients should be provided with a bespoke treatment plan following an MDT approach.
What are the 4 themes for identifying frailty?
- Cumulative impairment methods – CSHA 70 point score of multimorbidity. This refers to the ‘Jenga theory’ of removing important functions to cause overall collapse. These are the GOLD standard for frailty assessment.
- Phenotypical measures: The Freid et al model uses weight, hand grip weakness, exhaustion, slowness of walking speed and low physical activity level. This provides a quantitively result for research but is limited for cognitive impairment and severe frailty.
- Surrogates: The Bournemouth criteria determines who is eligible for the frailty service. Anyone aged over 90 is eligible. Otherwise patients aged 75-89 with 2 of the following: Immobility, incontinence, instability, intellectual impairment or iatrogenesis (polypharmacy over 5 medications). It will also be given to those over 65 who reside in a nursing or residential home.
- The Clinical Frail Scale is a descriptor method. It is all about the baseline and can only be used in over 65s. If someone has a terminal illness, they are CSF 9 because there is an expected deterioration. This score can be used in patients with dementia.
What are the implications of frailty?
Frailty has a dramatic impact on mortality. There is an increased risk of hip fracture, hospitalisation, ED admission, and poorer outcomes in renal transplant/general surgery/cardiac interventions.
What is a comprehensive geriatric assessment?
Comprehensive geriatric assessment is a multi-professional holistic assessment of a patient and must be patient centred. It include assessment of domains of health and the aim is to formulate a bespoke individual care plan.
CGA is done in response to age or efrailty scoring. Other indications for CGA are acute illness, high healthcare utilisation, change in circumstances, frailty syndromes and chronic disease. The care plan should then be implemented, monitored and further MDTs may be needed to revise a care plan.
Physical assessment should identify any acute illness, chronic illness, pain, nutrition status and assess continence. Gait and balance should be assessed somewhere that the patient knows well (home) and should also include footware assessment and lying/standing BP. Functions (ADLs) and sensory loss should also be assessed.
Psychological assessment should include mood assessment, sleeping, suicidal ideation, drugs, alcohol, depression, grief, loneliness, and cognitive assessment.
Social assessment includes support which may be beneficial, maintaining independence, beware of overprescribing, environmental assessment and telecare (falls alert technology).
Medication review is essential as polypharmacy is linked with poor concordance, increased risk of interactions, increased risk of falls, and cognitive decline so the benefits and risks should be weighed up. Beware of the prescribing cascade. Review medication indications.
Therefore, the CGA brings together these assessments to create a care plan. This should be a multifactorial plan for all domains and a schedule for monitoring and review should be established for each element.
What is an advanced care plan vs an anticipatory care plan?
ACP is an advanced care plan. These are usually put in place to refuse a future potential treatment such as ventilation. It must be in writing and state ‘even if life is at risk’ to refuse life prolonging treatment.
AnCP is an anticipatory care plan and is not an end-of-life plan. They are designed to reduce the risk to the patient by anticipating medical crises and planning a response.
Who can implement a DNACPR?
DNACPR is a medical decision. Patients cannot demand CPR is it is deemed to inappropriate but there is a legal requirement to inform the patient if a DNACPR is put in place.
Describe some common lung conditions on post mortem
In lobar pneumonia there is complete consolidation of an entire lobe with sparing of the other lobes. In Bronchopneumonia the consolidation follows the airways from the main bronchus.
Lobar pneumonia is much less common than bronchopneumonia and is predominantly caused by streptococcus pneumoniae. Severe pneumococcal pneumonia has a mortality around 20%.
Empyema will have pus like exudate with granulation tissue growing into the pleura and pus in the pleural space. It is often a continuation of a pneumonia but can occur spontaneously.
Abscessing bronchopneumonia is where the pus-filled space is in the lung parenchyma following pneumonia.
In aspiration pneumonia the airways are not filled by inflammatory cells but they are present in the interstitium between alveoli. This is then expanded by chronic inflammatory infiltrate which includes multinucleated giant cells which respond to the presence of foreign bodies.
Viral pneumonia does not have airways filled with inflammatory cells but there is infiltration by lymphocytes in the interstitium. COVID causes clotting instead. Viral pneumonia can be caused by influenza A and B, parainfluenza, adenovirus, human metapneumovirus and RSV (mainly children but can affect the eldery). Cytomegalovirus can appear in immunocompromised.
Bronchiectasis is peripheral airways becoming enlarged and cartilaginous due to repeated cycles of infection. This is due to inability to clear secretions from motility disorders, cystic fibrosis, localised established infection and mechanical obstruction such as a tumour.
Chronic bronchitis is a clinical diagnosis and not a pathological diagnosis. COPD is also a combination of chronic bronchitis and emphysema. They will have large emphysematous spaces in the lung. There will be half as many air spaces because the spaces have become enlarged.
Fibrous plaques form in the pleura and are associated with asbestos exposure. They are usually picked up on imaging. They do not cause harm themselves. It takes decades for asbestos pathology to present. Asbestos can cause interstitial lung disease but it is best known for increasing risk of malignancy, especially mesothelioma.
Honeycomb lung is seen in interstitial fibrosis occurring as the end stage of interstitial lung diseases. These are completely non-functioning lung.
Diffuse alveolar damage is an interstitial change pathological caused by acute respiratory distress syndrome. This is why there is white out of both lungs because the lung tissue has been replaced with fibrous tissue. It has a very high mortality.
What are the presentations of bowel conditions post-mortem?
Diverticuli are very common in elderly patients (around 60%). BPH is also extremely common.
Pathology of small bowel ischaemia and atherosclerosis were also discussed in this lecture. Know the presentation of these syndromes in the elderly for the exam!!!
Pseudomembranous colitis is caused by c.difficile . Patients on long term antibiotics develop this. The neutrophils cause the volcanic appearance of the pseudomembrane.
How does GORD cause Barrett’s?
GORD causes obliteration of the gastro-oesophageal junction. This is caused by Barrett’s like changes.
When should a renal biopsy be done?
Purpose is to establish a tissue diagnosis, assess the severity/activity of disease, or to assess the amount of irreversible damage/tubular atrophy/glomerular sclerosis. 7-10 glomeruli need to be taken for an adequate reading without damaging the kidney. It is important that the site of biopsy is noted as subcapsular biopsies have a tendency to overestimate the global sclerosis related to ageing, hypertension or non-specific scarring.
How are renal biopsy findings described?
Focal glomerular changes: Under 50% of the glomeruli are affected
Diffuse glomerular changes: Over 50% of the glomeruli are affected
Segmental glomerular changes: involving part of the glomerular tuft of a single glomerulus
Global glomerular changes: Involving all of the glomerular tuft of a single glomerulus
Acute lesions: Usually means recent and reversible damage such as glomerular proliferation, interstitial inflammation, and acute tubular necrosis
Chronic lesions: Irreversible damage such as glomerulosclerosis, interstitial fibrosis and tubular atrophy.
What are the classifications of acute renal failure?
This can be divided into three clinical patterns:
1. Pre-renal
2. Renal/intrinsic
3. Post-renal
Describe pre-renal causes of AKI
Pre-Renal is caused by decreased renal perfusion. Causes can include heart failure, volume loss (D+V, burns, internal or external haemorrhage), or systemic arteriolar vasoconstriction (NSAIDs and radiocontrast). Biopsy should not be performed when pre-renal is suspected.
If a biopsy is taken there will be non-specific findings but the general effect of hypoxia or ischaemia. There may be acute tubular necrosis (reversible) or partial collapse of glomeruli. On histology there will be swelling of the cytoplasm, eosinophilia, vacuolation and loss of nuclei. The collapse of glomeruli is also reversible and visible on histology.
What are the glomerular (renal) causes of AKI?
Glomerular: Glomerulonephritis can cause acute renal failure and usually falls into a class referred to as a rapidly progressive glomerulonephritis (RPGN) or crescentic glomerulonephritis. The pathologic feature of RPGN is the prescence of glomerular crescents. This is reversible.
Crescents can be cellular, fibrocellular, or fibrous depending on their composition. They are caused by the proliferation of parietal epithelial cells in response to an injury that breaks the capillary wall which can then be associated with necrosis. The aetiology can be autoimmune (Anti-GBM, IgA or MGM) or immune complex modulated (ANCA associated vasculitis).
What are the vascular (renal) causes of AKI?
: Large vessel obstruction such as renal artery (thrombosis, emboli or dissection) or renal vein (thrombosis). Small vessels can also caused ARF (Haemolytic uraemic syndrome, DIC, and pre-eclampsia) and malignant hypertension will affect the kidneys.
Cholesterol emboli are common causes of unexplained ARF in elderly patients. Predisposing factors include trauma, surgery, and anticoagulation. This may be slowly progressive and involve the glomeruli. Pre-eclampsia on histology will show endothelial swelling which causes an obstruction, this is reversible damage. Infraction is irreversible damage. Microangiopathy will have micro-thrombi filling the glomeruli capillary lumens and hence renal ARF.
Malignant hypertension presents on histology with intimal proliferation of spindle cells in the walls of the arteries and hence lumen obstruction. This shows as an onion skin appearance. This is reversible so the aim is to improve their blood pressure and prevent the development of fibrous tissue.
What are the tubular (renal) causes of AKI?
The most common cause of tubular ARF is ischaemic or cytotoxic acute tubular injury. Frank necrosis is not prominent in most cases of ATN and tends to be patchy. Cytotoxic events include rhabdomyolysis (remember cocaine can cause this), lithium, NSAIDs and radiocontrast agents.
On histology, rhabdomyolysis will show myoglobin blockage causing ATN. This can be reversible. The timing of the biopsy is important as only early on will the specialist staining for myoglobin pick anything up.
What are the interstitial (renal) causes of AKI?
The main cause of this is inflammation otherwise known as tubulointerstitial nephritis. This can be caused by drugs (penicillin, NSAIDs), infection (pyelonephritis), and systemic disease (sarcoidosis, lymphoma, and leukemia). There will be inflammatory infiltration on histology.
Tubular interstitial necrosis is a non-specific diagnosis and an underlying cause should be sought:
- Intratubular polymorphonuclear neutrophils forming plugs are diagnostic of acute pyelonephritis
- Eosinophils in the interstitium can indicate a drug reaction
- Granulomas can indicate a drug reaction. Confluent granulomas point to sarcoidosis whereas necrotising granulomas are indicative of infection (especially TB or fungus)
Deposition of casts is most commonly oxalate in oxalosis (primary or secondary such as ethylene glycol ingestion or jejunal interstitial bypass). On histology they appear like shining glass because they are reflecting the light back at the microscope.
What are the post-renal causes of AKI?
Post-renal causes include urinary tract obstruction which increases the intra-tubular pressure and thus decreases GFR. Acute obstruction can also lead to impairment of the renal blood flow and inflammatory reaction which will further diminish GFR/ Obstruction of the urinary tract at any level can produce AKI. Treatment is to manage the cause.
Which systemic diseases can cause AKI?
Diabetic nephropathy, papillary necrosis, systemic hypertension, amyloidosis, and multiple myeloma.
How does AKI develop in renal failure?
- Acute cellular mediated rejection
- Acute antibody mediated rejection
- Acute ischaemic injury/acute tubular damage
- Calcineurin inhibitor nephrotoxicity (cyclosporine and tacrolimus)
- Major artery/vein thrombosis
- Renal artery stenosis
- Obstruction
- Infection
- Acute tubule-interstitial nephritis (drug allergy)
- Recurrent primary disease
What is CKD and what are the most common causes?
Chronic renal failure is caused by a progressive decline in all kidney functions, ending in terminal kidney damage. The most common causes are diabetic nephropathy, hypertensive nephropathy, primary glomerulonephritis, TIN, and recurrent infection.
There is a reduction in nephron numbers, hyper-filtration of remaining nephrons (glomerular enlargement), proteinuria and HTN, acute tubular damage, inflammation, segmental glomerulosclerosis, interstitial fibrosis, and tubular atrophy which further reduces nephron numbers.
How does renal impairment impact pharmacotherapy?
Drugs are generally excreted in the kidneys, and this occurs in a variety of ways. Most drugs have a component of renal excretion. Drugs are generally filtered into the bowman’s capsule, and this is dependent on renal blood flow and glomerular filtration rate. Drugs that are protein bound will not be filtered as they are too large to move into the capsule.
Secretion occurs when a drug has a specific mechanism that allows transport into the kidney tubule, usually the proximal tubule. The two main transporters involved in this process which are the OAT transporter which transports organic anions and the OCT transporter which transports organic cations. These are an important mechanism for drugs which are protein bound.
Reabsorption mainly occurs in the distal tubule. The drugs which are more likely to be reabsorbed are lipophilic which enables them to pass through the epithelial aspects of the tubule and into the bloodstream. The polarity of drugs and metabolites is affected by the urine pH and that may affect their ability to diffuse across those membranes.
Patient factors mainly impact filtration. Renal impairment is defined as AKI or CKD.
The KDIGO classification for AKI
The KDIGO classification of chronic kidney disease
Renal impairment impacts the renal handling of drugs. Patients with CKD are more susceptible to side effects and tolerate them poorly. In terms of pharmacokinetic effects there is reduced renal clearance which leads to higher steady-state concentrations. For drugs with a narrow therapeutic index this may lead to toxicity. The most important drugs in this context are those with a high proportion of renal clearance (the fraction excreted unchanged) and a narrow therapeutic index.
The pharmacodynamic effects include sensitivity to some drugs being increased by renal impairment and some drug effects may be attenuated by renal impairment.
How does hepatic impairment impact pharmacotherapy?
The liver is the main site of drug metabolism as it is involved in the conversion of the active, lipid soluble drug to inactive hydrophilic metabolites. (Codeine to morphine). This generally results in detoxification and elimination. Sometimes metabolism is required to convert a pro-drug to an active form. The liver is exceptionally important for protein bound drugs such as phenytoin and prednisolone. Biliary excretion is not a major route for drug elimination, but important for some such as rifampicin and fusidic acid.
Reduced metabolism in severe liver disease cannot be determined from routine LFTs. It is most likely in parenchymal liver disease (hepatitis or alcohol) because the liver has a huge hepatic reserve so can usually compensate before hepatic impairment causes reduced metabolism. This causes a slower metabolism of the parent compound and hence reduced clearance rate, elevation of serum concentration of the parent compound, leads to increased and prolonged drug effect, increased risk of adverse drug reactions, especially for drugs with a narrow therapeutic index, increased risk of drug-drug interactions and reduced efficacy or pro-drugs (codeine). Further, there is a serious risk of overdose on morphine due to reduced first-pass metabolism of drugs which high hepatic extraction.
The reduced protein production means lower circulating albumin levels. This means reduced protein binding of drugs, increased proportion of free drug and thus increased receptor-binding/drug effect/toxicity (phenytoin and prednisolone).
The reduction of clotting factors causes prolonged prothrombin time and thus increased sensitivity to oral anticoagulants (warfarin).
Reduced biliary excretion is found in cholestatic liver disease such as primary biliary cirrhosis. This leads to reduced biliary excretion and accumulation of those drugs with major elimination by this route as seen in rifampicin and fusidic acid.
Hepatic encephalopathy can be worsened or caused by drugs including sedatives, opioids, diuretics producing hypokalaemia, and constipating drugs. Fluid overload may also be exacerbated by drugs that promote fluid retention (NSAIDs and corticosteroids) and when there is fluid overload a higher dose of digoxin may be needed to reach therapeutic range. Hepatotoxity is a feature of many medications which can be dose dependent or idiosyncratic (unpredictable hepatic toxicity).
Which drugs require special consideration when used in renal impairment?
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.
How should warfarin and paracetamol be prescribed in hepatic impairment?
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.
What are the consequences of polypharmacy?
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
Which conditions in the elderly should not be treated with medication?
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.
Which drugs commonly cause admission to hospital in the elderly?
Antiplatelets (aspirin), diuretics, NSAIDs, anticoagulants, opioids, beta-blockers, ACE-I/ARBs, and hypoglycaemic agents.
What is the prescribing cascade?
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.
What are the pharmacokinetic changes in older people?
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).
What are the pharmacodynamic changes in older people?
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.
What is polypharmacy?
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
What is deprescribing?
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.”
What is medicinal optimisation?
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.
What are the causes of haematuria on a urine dipstick?
Infection, tumour, and glomerular dysfunction
What are the causes of haemoglobuliinuria?
Intravascular haemolysis
What are the causes of myoglobulinuria?
Rhabdomyolysis
What is the significant of dysmorphic erythrocytes on urine microscopy?
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.
How should ACR and PCR be used in relation to proteinuria investigations?
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.
How is proteinuria divided into nephrotic and nephritic syndrome?
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.
Summarise diabetic nephropathy
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.
Summarise hypertensive nephropathy
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:
- Medial and intimal thickening, as a response to haemodynamic changes, ageing, genetic defects, or some combination of these
- 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.
How does SLE cause renal damage?
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
How does progressive systemic sclerosis cause renal damage?
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
How does Sjoegren’s syndrome cause renal damage?
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.
How does myeloma affect the kidneys?
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.
What is cryoglobulinaemia?
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.
What is Haemolytic Uremic Syndrome?
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.
How does Sickle Cell disease cause renal disease?
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.
How does vasculitis affect renal function?
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.
What is in a renal blood screen?
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.
How should a renal biopsy be taken?
A kidney biopsy should be taken from the lower 1/3 of the kidney. A kidney biopsy has three stages:
- Hematoxylin-eosin stain for mesangial expansion or hypercellularity
- Immunofluorescent microscopy for IgA deposition or other antibodies within the glomerular mesangium
- Electron microscopy for significant expansion of the mesangial matrix and presence of large mesangial dense deposits.
What is IgA nephropathy?
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.
What is secondary IgA nephropathy?
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.
What is Alport’s disease?
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.
What is thin membrane disease?
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
What is the treatment for IgA nephropathy?
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.
What are connective tissue diseases?
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.
What is systemic sclerosis?
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.
What is systemic Lupus Erythematosus?
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.
What is Sjogren’s syndrome?
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.
What are polymyositis and dermatomyositis?
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.
What is Giant Cell Arteritis?
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.
Describe some small vessel vasculidities
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).
How are inflammatory and mechanical arthritis separated?
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.
Summarise rheumatoid arthritis diagnosis and investigations
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
What are the radiographic changes in rheumatoid arthritis vs osteoarthritis?
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
