Medicine 1 Flashcards
What is DM?
= a multisystem disease resulting from inadequate secretion/action of insulin, resulting in disturbances of carbohydrate, fat and protein metabolism.
T1DM - pathophysiology
An autoimmune disease
=> Antibodies targeted against the insulin-secreting beta cells of the islets of Langerhans in the pancreas.
=> Leads to cell death and inadequate insulin secretion.
Can be idiopathic, or sometimes viral infections can trigger the autoimmune process.
T1DM - presentation
Typically presents in childhood/adolescence, with a 2-6 week history of:
- Polyuria – high sugar content in urine leading to osmotic diuresis
- Polydipsia – due to resulting fluid loss.
- Weight loss – fluid depletion and fat/muscle breakdown.
DKA is also a common first presentation.
T2DM - pathophysiology
“Insulin resistance” – associated with aging, genetic factors, obesity, high fat diets and sedentary lifestyle.
Peripheral resistance – tissues become insensitive to insulin.
Blood insulin levels are initially normal, or even increased to compensate for insensitivity to insulin.
Eventually pancreatic beta cells decompensate and can no longer produce excess insulin, leading to hyperglycaemia.
T2DM - presentation
Onset may be over many months/years.
Classic triad of symptoms (polyuria, polydipsia, weight loss) may be present, but less noticeable than T1DM.
More common presenting features:
- Lack of energy
- Visual blurring – glucose-induced refractive changes.
- Pruritis vulvae/balantis – due to candida infection.
In older patients, it may be the COMPLICATIONS of diabetes that are the presenting feature.
Metabolic syndrome
T2DM,
Central obesity,
HTN
What is MODY?
= maturity-onset diabetes of the young
Genetic defect – autosomal dominant inheritance
Defects in beta-cell function.
Usually affects those <25 years of age.
Mimics T1DM
What is secondary diabetes?
Diabetes due to other conditions/causes precipitating the diabetes (~1% of cases)
Pancreatic disease:
=> CF, chronic pancreatitis, pancreatic carcinoma, pancreatic trauma/surgery.
Endocrine disease:
=> Cushing’s disease, acromegaly, thyrotoxicosis, phaeochromocytoma.
Drug-induced:
=> thiazide diuretics, corticosteroids, antipsychotics, antiretrovirals.
Congenital:
=> insulin-receptor abnormalities, myotonic dystrophy, Friedrich’s ataxia.
Gestational diabetes
Infections – congenital rubella, cytomegalovirus, mumps
Insulin release post-meal
Insulin is released by beta cells when glucose levels rise after a meal.
Insulin acts upon glucose transporters (GLUTs).
=> GLUT2 – senses glucose in beta cells.
=> GLUT4 – insulin-mediated glucose uptake in skeletal muscle and adipose tissue.
Insulin’s anabolic effects result in glucose being converted to:
- glycogen in muscle,
- glycogen and triglycerides in the liver
- triglycerides in adipose tissue.
Glucagon in starved state
insulin production is down-regulated;
alpha-cells of the pancreas will release glucagon, which works to:
- Increase glycogenolysis
- Increase gluconeogenesis
- Inhibit glycogen synthesis
DM - diagnosis
BEDSIDE TESTS
- Urine dipstick – can identify glycosuria and ketonuria (maybe proteinuria if nephropathy)
- Random glucose test
BIOCHEMICAL TESTING:
- Fasting blood glucose (minimum fast of 8 hours).
- Oral glucose Tolerance Test (OGGT) – 75mg glucose bolus, test 2 hours later.
- HbA1c – used for monitoring and screening; does not require the patient to be fasted.
In what populations is HbA1c testing innapropriate?
- Those <18 years old.
- Those acutely unwell (glucose temporarily raised in infection/steroid use)
- Pregnancy
- Haemoglobinopathies
- Increased RBD breakdown
In the presence of signs and symptoms, what blood test results are needed for a diagnosis of DM?
Fasting plasma glucose values of ≥ 7.0 mmol/L (normal <6.0 mmol/L)
or
Oral Glucose tolerance test (OGTT) – 2-hour plasma glucose ≥ 11.1 mmol/L (normal <7.8mmol/L).
or
HbA1c ≥ 48 mmol/mol (normal <42 mmol/mol)
or
Random blood glucose ≥ 11.1 mmol/L
In the absence of signs and symptoms, what blood test results are needed for a diagnosis of DM?
Any of the blood glucose tests with a value above the cut-off, but a repeat test (ideally same one) as soon as possible.
Impaired Fasting Glucose (IFG)
Fasting plasma glucose = 6.1 mmol/L to 6.9 mmol/L.
Normal 2-hour plasma glucose (<7.8)
Impaired Glucose Tolerance (IGT)
2-hour plasma glucose = 7.8 mmol/L to 11.0 mmol/L.
Normal fasting plasma glucose.
What is Pre-diabetes?
HbA1c is not at the diabetic level, but not normal either (i.e. 42-47 mmol/mol)
T2DM – overview of Mx
Typically conservative/lifestyle measures for 3 MONTHS
then re-check HbA1c
Start anti-diabetic drugs if HbA1c still high (58 mmol/L (7.5%) or higher)
T2DM – Conservative Mx
Structured group education programme.
Screen for complications at diagnosis, (then repeat annually):
- Fundoscopy
- Nephropathy screen – urine dip for protein (or microalbuminuria = more sensitive).
- Foot Check – for neuropathy, ABPI, ulcers, deformity.
Monitor CV Risk
Lifestyle advice:
- Maintain a healthy diet (can see a nutritionist to help with meal plans).
- Weight loss if overweight
- Increase physical activity – 20-30 mins brisk walking per day.
- Stop smoking (to reduce CV risk).
- Reduce Alcohol
How is CV risk monitored in DM?
Control BP to <140/80 (<130/80 if kidney, eye or cerebrovascular damage).
Assess QRISK2 score – offer atorvastatin 20mg for those with 10-year risk >10%.
Why is it important to counsel diabetics on alcohol use?
Alcohol may prolong the effect of hypoglycaemic drugs
May make the signs of hypoglycaemia less clear.
Always have a carbohydrate snack before and after consuming alcohol.
T2DM – Medical Mx
1st LINE = metformin
=> if metformin contra-indicated, one of the other antidiabetic drugs
2nd LINE
- Metformin + 2nd drug
- If metformin is contraindicated, any 2 of the other anti-diabetic drugs.
3rd LINE
triple therapy
4th LINE
- If metformin contraindicated/triple therapy not effective, consider insulin regimens.
What is the starting dose of metformin for a patient?
500mg with breakfast for one week
500mg with breakfast and dinner for one week
500mg with breakfast, lunch and dinner thereafter
Do T2DM patients need to self-monitor blood glucose?
Self-monitoring blood glucose kits are not routinely required in adults with T2DM, but may be advised if the patient is at risk of hypoglycaemic events.
T2DM - insulin therapy
Continue metformin Tx to prevent excess weight gain.
Immediate acting insulin injected once/twice daily according to need.
Biphasic preparations can be used if the Pt’s HbA1c is particularly high.
T1DM Mx
Structured education programme
=> DAFNE – dose-adjustment for normal eating.
Screen for complications (less common in early-onset disease)
Monitor CV risk
Lifestyle advice:
- Diet – carbohydrate counting is the most important advice, as per DAFNE education.
- Advice for how to adjust diet/insulin for exercise and consuming alcohol.
Insulin regimen
Annual review
When is insulin therapy indicated?
- all patients with T1DM that present below the age of 40
- all patients with T2DM that fail to respond to full medical Tx / are unsuitable for medical Tx
What is the typical insulin regimen for a T1DM patient?
basal bolus regimens are recommended:
- Twice daily long-acting insulin – e.g. Detemir
- Rapid acting insulin with each meal – e.g. Novorapid.
If this is not possible, twice-daily mixed insulin regimens can be tried.
If the patient cannot achieve HbA1c <8.5%, insulin pumps can be considered by a specialist team.
Sick Day Rules for insulin
The body’s natural response to illness results in higher blood glucose levels due to the release of stress hormones and release of glucose from your body’s stores.
- DO NOT STOP INSULIN – seek advice from diabetes team on how to adjust insulin dose.
- Monitor Blood glucose more frequently.
=> Every 3-4 hours, including overnight. - Consider blood/urine ketone monitoring:
=> If raised, contact GP/diabetic service immediately. - Maintain normal meal pattern where possible.
=> Replace meals with sugary drinks if appetite reduced. - Drink at least 3L of fluid per day:
=> Seek advice if unable to do so
=> IV fluids may be needed - Once better, continue to control blood glucose carefully until it returns to normal.
When are diabetic patients required to inform the DVLA?
Patients are only required to inform the DVLA if:
- They have had 2 episodes of severe hypoglycaemia within the last 12 months.
- They have reduced awareness of hypoglycaemic episodes
- They are on insulin therapy:
=> If on insulin, they must test their blood glucose every 2 hours on long journeys and also carry appropriate glucose stores in case of hypoglycaemic events.
Components of an Annual Diabetes Review
- Assess Cardiovascular Risk
=> BMI, BP, Smoking Status, Blood lipid levels, Consider ECG - Assess for microvascular complications:
- Hx – erectile dysfunction, neuropathic pain
- Foot examination (incl. neurovascular status)
- Fundoscopy – retinal involvement
- Urine dip, first pass urine and plasma creatinine – renal involvement - Assess Diabetic Control:
- Self-monitoring results?
- HbA1c (should be checked 6-monthly) - Assess for concordance to diet/lifestyle advice
- Assess for adverse events:
- Hospitalisations
- Sx of hypoglycaemic episodes
- Medication side effects
- Injection site reactions - Is the patient driving?
=> If so, do they know the DVLA advice. - Assess for depression and anxiety
Metformin - MOA
- Decrease hepatic glucose production
- Increase peripheral insulin sensitivity
Metformin - contraindications
- eGFR <30 for standard release, <45 for modified release.
- Alcohol addiction
- People at risk of lactic acidosis (e.g. DKA)
- People at risk of tissue hypoxia (e.g. cardiac/respiratory failure).
Metformin - SEs
GI effects – N&V, abdo pain, loss of appetite
Lactic acidosis – rare but serious; occurs due to drug accumulation; insidious onset with non-specific symptoms; more common when combined with alcohol.
Vitamin B12 deficiency
Sulphonyureas - MOA
Increase insulin secretion (thus only work if some residual function of pancreatic beta-cells).
Can get different lengths of drug action:
- SA – tolbutamide
- Medium acting – gliclazide
- LA – Glibenclamide (rarely used if there is a risk of hypoglycaemia).
When are sulphonyureas prescribed with caution?
The elderly – risk of hypoglycaemic events
The obese – will encourage weight gain
SGLT-2 inhibitors - MOA
Inhibit sodium-glucose transport protein 2; thereby preventing renal glucose resorption.
NOT effective in kidney disease
Help weight loss & reduce risk of major adverse CV events
Thiazolidinediones - MOA
PPAR-gamma activators; increase peripheral insulin sensitivity.
Thiazolidinediones - SEs
Weight gain (redistribution of ectopically stored lipid)
Fluid retention – contraindicated in CCF
Liver dysfunction – monitor LFTs
Association with bladder cancers – assess risk factors
DPP-4 inhibitors - MOA
work by increasing post-prandial insulin release.
When are GLP-1 Mimetics used?
E.g. enaxatide; liraglutide
Cause significant weight loss
NICE recommend that if triple therapy is ineffective, then the gliptin/pioglitazone can be replaced by GLP-1 mimetics if:
- The patient has BMI >35
- The patient has BMI <35 and weight loss would benefit other comorbidities/insulin therapy would have negative occupational impacts.
Short-acting insulins
e.g. Humalog, Novarapid
Aim to mimic the body’s insulin secretion in response to food.
Injected with food
Onset of action = 15 mins
Soluble insulins
e.g. Actrapid, Humalin S
(also short-acting)
Generally injected 30 mins before food.
Onset of action = 30-60 mins
Duration of action = up to 8 hours
Intermediate-acting insulins
e.g. Humalin I, Insulatard
Mimic basal insulin secretion
Onset of action = 1-2 hours
Maximal effects between 4-12h
Duration of action up to 16-35 hours
Long-acting insulins
e.g. Lantus, Levemir, Tresiba, Detemir
Mimic basal insulin secretion
Used once/twice per day
Achieve a steady-state level after 2-4 days.
Complications of insulin therapy
- Weight gain (avoided by DAFNE)
- Insulin resistance can develop
- At the injection site – pain, redness/swelling, abscess, lipohypertrophy (can result in erratic insulin absorption).
How do macrovascular complications of DM occur?
Hyperglycaemia leads to formation of advanced glycation end products (AGE) on arterial endothelial cells and activation of inflammatory pathways
This exacerbates the process of atheroma formation, leading to artery occlusion and subsequent macrovascular complications.
How do microvascular complications of DM occur?
occur via AGE-activated biochemical pathways resulting in cellular damage caused by abnormal extracellular protein matrix accumulation and reactive oxygen species production.
=> Microvascular complications are specific to diabetes.
Macrovascular complications of DM
Coronary Artery Disease (=> 4x increased risk of MI)
Cerebrovascular Disease (=> 2x increased risk of Stroke)
Peripheral Vascular Disease
Microvascular complications of DM
Diabetic Eye Disease
Nephropathy
Neuropathies
Preventing complications of DM
MACROVASCULAR
Good glycaemic control only has modest effects on CV risk – need to work on other factors such as smoking/alcohol, BP, cholesterol, diet, exercise, etc.
MICROVASCULAR
Regular screening
Good glycaemic control
Proliferative diabetic retinopathy (PDR)
= development of new vessels on the optic disc/retina as a response to significant retinal ischaemia (VEGF => new vessels).
The vessels are fragile and likely to bleed; giving rise to pre-retinal or vitreous haemorrhage.
If untreated, the blood vessels will cause fibrosis and a tractional retinal detachment
Tx:
- Pan-retinal photocoagulation (aim = to reduce the ischaemic drive and VEGF production).
- Vitrectomy can be used to remove persistent vitreous haemorrhage.
Non-proliferative diabetic retinopathy (NPDR)
Usually asymptomatic
ALWAYS occurs at some severity after 8-10 years of DM
Features on fundoscopy:
- Microaneurysms
- Exudates
- Haemorrhages – dot, blot, flame
- Cotton wool spots (>5 of these indicated pre-proliferative retinopathy).
Can progress to PDR
Mx = good glycaemic control
Diabetic Maculopathy
A specific type of retinopathy that affects the macula.
Typically presents with blurring of vision
Three subtypes – focal, diffuse, ischaemic
Mx = focal laser to stop focal leaks, but may require more complex Tx
What forms of diabetic eye disease are there?
PDR / NPDR
Maculopathy
Cataracts
Glaucoma
What are the possible diabetic neuropathies?
Symmetrical Polyneuropathy
Acute Painful Neuropathy
Mononeuropathy
Diabetic Amyotrophy
Autonomic Neuropathy
DM - Symmetrical Polyneuropathy
“Glove and stocking” sensory loss
=> Vibration, deep pain and temperature lost first
Loss of proprioception
Interosseus wasting of small muscles of the feet results in a characteristic foot shape, and abnormal pressure areas lead to ulcers.
Unrecognised trauma with poor wound healing may lead to ulcers
=> Can lead to Charcot’s foot
DM - acute painful neuropathy
Painful burning pains in the feet, shins and anterior thighs; Typically worse at night
Associated with poor glycaemic control
Usually remits after 3-12 months of good glycaemic control.
More chronic forms can be resistant to all forms of therapy.
DM - mononeuropathy
Cranial Nerve lesions can occur in patients with diabetes – mainly CN III, IV and VI (ocular palsies).
Isolated peripheral nerve lesions can also occur
Any nerve compression syndrome is more common in DM (e.g. carpal tunnel)
Foot drop may occur due to lesions of the sciatic nerve.
When more than one nerve is affected, this is known as mononeuritis multiplex.
DM - amyotrophy
Amyotrophy = progressive wasting of muscle fibres.
In DM, it presents as painful wasting of the quadriceps
Course is variable, often with gradual but incomplete improvement.
DM - autonomic neuropathy
Sympathetic dysfunction leads to:
- Postural hypotension
- Ejaculatory failure
- Reduced sweating
- Horner’s syndrome
Parasympathetic dysfunction leads to:
- Erectile dysfunction
- Constipation
- Urinary retention
- Holmes-Adie Pupil
DM - identifying and managing renal complications
Usually manifests 15-25 years after diagnosis
The single most important intervention is BP control
Test every patient every 6 months for microalbuminuria (i.e. negative urine dip but early morning albumin:creatinine ratio >3)
Every patient with microalbuminuria should be started on an ACEI, regardless of BP.
What is DKA?
= a medical emergency, in which hyperglycaemia is associated with metabolic acidosis due to greatly raised ketone levels.
DKA - Presentation
SYMPTOMS
- N&V
- Generalised abdominal pain
- Confusion / drowsiness
- Blurred vision
- Polyuria
- Coma (severe cases)
SIGNS:
- Smell of ketones on the breath
- Signs of dehydration
- ABG/VBG will show an acidosis (or compensated acidosis) due to bicarbonate consumption by acidic ketone bodies. Lactate levels will also be raised.
DKA - diagnosis
all 3 required:
- Blood glucose >11 mmol/L (or previously known diabetes).
- Capillary ketones >3 mmol/L (or Ketones >2+ in urine).
- Venous pH <7.35 (or venous bicarbonate <15 mmol/L)
DKA - Ix
U&Es
Blood glucose
Venous blood gas
=> Metabolic acidosis with raised anion gap
ECG/ CXR / cultures / pregnancy test based on clinical suspicion to identify cause
DKA - severity
Severity is determined by pH rather than blood glucose:
- Mild = pH >7.3
- Moderate = pH 7.1-7.3
- Severe = pH <7.1
DKA - immediate Mx
ABCDE
1L 0.9% sodium chloride over 1 hour if SBP >90
=> 500 ml bolus over 10 mins if <90, reassess & repeat if poor response
Start IV insulin infusion:
=> 50 units human soluble Actrapid Insulin added to 50ml 0.9& sodium chloride (giving a 1 unit / mL solution)
=> Start syringe driver at a fixed rate of 0.1 units/kg/hour (can use estimated weight).
Treat any precipitating factors of the DKA (e.g. infection).
Urgent critical care review if:
=> severe DKA / drowsy / pregnant / sats <94% / on 40% oxygen / persistent hypotension after 2L sodium chloride.
DKA - ongoing management
Continue fixed-rate insulin at 0.1 units/kg/hour, and continue normal long-acting insulin.
Continue IV 0.9% sodium chloride
- First bag = 1L over 1 hour
- Second bag = 1L over 2 hours
- Consider KCl from second bag onwards
- Third bag = 1L over 2 hours
- Fourth bag = 1L over 4 hours.
When glucose is <14 mmol/L, add 10% glucose at 125 mL/hour
=> Adjust to keep blood glucose between 8-14 mmol/L
Potassium:
- If plasma K+ <5.4, add 40 mmol KCl per litre NaCl
- Consider after the first litre of fluid has run through
Clinically reassess the patient hourly for the first 4-6 hours
Regular lab monitoring of glucose, ketones, potassium and bicarb required.
DKA - Mx after recovery
Transfer to s.c. insulin once the patient is able to eat and drink normally and venous pH >7.3
Stop the IV insulin infusion 1 hour after the next s.c. injection of insulin
Refer all patients to the diabetes team prior to discharge.
What is HHS?
= a severe hyperglycaemia leading to diuresis (leading to a hyperosmolar state) in the absence of severe ketosis and acidosis.
Even a small amount of insulin is sufficient to prevent ketosis.
The patients will be more severely dehydrated than DKA patients, but there will be no raised ketones.
Mortality is 10x more likely in HHS than DKA
HHS - presentation
- Dehydration
- Stupor/coma/seizures
- Evidence of an underlying illness
HHS - diagnostic criteria
Marked hyperglycaemia (often >30 mmol/L)
Hypovolaemia
No significant ketonaemia/ketonuria
No significant Acidosis (pH >7.3, bicarb >15mmol/L)
Confirm by calculating osmolality
=> Normal Osmolality = 280-295 mmol/kg; HHS = >320 mmol/kg
Why is fluid replacement more important than insulin in HHS?
Fluid replacement alone will cause the glucose levels to fall.
Insulin treatment prior to adequate fluid replacement may result in cardiovascular collapse as water moves out of the intravascular space, with a resulting decline in intravascular volume
HHS - Mx
A-E assessment
Aggressive IV fluids:
=> 1L 0.9% NaCl over 1 hour
=> Aim for positive balance of 3-6L over 12 hours.
Low-dose fixed IV insulin infusion:
=> If there are some ketones – treat as per DKA
=> If no ketones – fluid replacement alone should cause a fall in glucose.
=> Start insulin once fall in glucose is <5 mmol/L/hour = 0.05 units/kg/hour
Consider potassium replacement
Give prophylactic LMWH (due to very high risk of thrombosis)
Regular monitoring of vitals, fluid balance, glucose, osmolality, U&Es hourly for 1st 6 hours.
Transfer to s.c. insulin once eating and drinking normally and biochemistry has normalised
=> Stop IV infusion 1 hour after starting s.c. insulin
Refer to diabetes team
Hypoglycaemia
Defined as plasma glucose <3mmol/L, but individual thresholds for symptoms are variable.
Hypoglycaemia - Sx
AUTONOMIC
Sweating
Anxiety
Hunger
Tremor
Palpitation
NEUROGLYCOPAENIC
Confusion
Drowsiness / Coma
Seizures
Causes of hypoglyaemia
Excess insulin – either exogenous or insulinoma
Depletion of hepatic glycogen – malnutrition, fasting, exercise, alcohol; also liver failure.
(Pituitary insufficiency, adrenal insufficiency, non-pancreatic neoplasms)
Hypoglycaemia - Mx (if Pt able to swallow)
Promptly consume 10-20g of fast-acting form of carbohydrate (preferably liquid form).
Recheck blood glucose after 10-15 minutes.
- Should reverse in 10 mins
- Improvements in signs and symptoms may lag behind improvement in blood glucose.
If inadequate response, repeat as above and recheck again.
When symptoms improve, the patient should eat some long-acting carbohydrate.
Hypoglycaemia - Mx (if Pt unconscious / unable to swallow)
Administer IM glucagon immediately:
- If <8 years = 500 micrograms
- If >8 years = 1mg
If glucagon is not available, the patient has consumed alcohol, or the person does not respond to glucagon within 10 minutes – call 999 for emergency hospital transfer
=> Glucagon is NOT effective if alcohol has been consumed
If the patient responds to glucagon, advise intake of long-acting carbohydrates when able.
Vomiting is common in recovery, which can precipitate further episodes of hypoglycaemia.
Within hospital:
- 100ml of 20% glucose can be used as an alternative to glucagon (can be repeated 3 times).
- If IV access is not available, administer IM glucagon whilst gaining access.
Symptoms of Asthma
Symptoms tend to be variable but recurring:
- Wheeze
- SoB
- “Tight” chest feeling
- Cough (classically nocturnal)
Symptoms tend to be worse at night or early in the morning
Common precipitants to asthma symptoms
- Viral infections
- Cigarette smoke
- Cold weather
- Emotion
- Excercise
- Atmospheric pollution
- Pets / pollen / other allergens
- Occupational pollutants – e.g. flour/chemicals
Important points to establish in an asthma history
HPC
Known precipitants
Diurnal variation
Acid reflux symptoms (known association)
Hx of atopy
Hx of these episodes (incl. whether they required hospital admission/ITU)
DHx
NSAIDs
Beta-blockers
FHx
Atopy, asthma
SHx
Smoking
Days off work/school
Occupation (identify occupational pollutants)
Pets
Diagnosis of asthma
Asthma is a CLINICAL DIAGNOSIS – if there are suggestive symptoms, then a structured clinical assessment is needed to see if:
* Episodes are recurrent
* Sx are variable
* PMHx/FHx of atopy
* Recorded observation of expiratory wheeze
* Variable PEF or FEV1
* Absence of symptoms of an alternative diagnosis
If these give a high probability of asthma, diagnose as suspected asthma and initiate treatment.
DIAGNOSIS IS CONFIRMED AFTER AN OBJECTIVE IMPROVEMENT AFTER Tx
When might further Ix be needed for a diagnosis of asthma?
If response to treatment is poor, refer for spirometry to test for airway obstruction with bronchodilator reversibility
=> FEV1/FVC <70% with bronchodilator reversibility is diagnostic
Extrinsic Asthma
= Type I hypersensitivity reaction
Most frequently occurs in atopic individuals who show positive skin prick tests to common allergens, implying a definite extrinsic cause.
Intrinsic Asthma
= Due to non-immune mechanisms
Occurs in middle-aged individuals, when no causative agent can be identified.
Generally more severe, and associated with quicker deterioration of lung function.
Pathophysiology of asthma attack
Acute episodes of bronchospasm that are triggered by recognised triggers.
Triggers activate mast cells, which lead to two phases of airway narrowing
Early phase – bronchospasm due to spasmogen production (histamine, PG D2, leukotrienes) causing smooth muscle contraction in the airways.
Late phase – due to chemotaxins causing an inflammatory response, causing narrowing of the airways).
There will also be airway hyper-reactivity in the late phase, which can lead to further acute deterioration.
Aims of long-term Mx of asthma
no daytime Sx,
no night-time waking,
no need for rescue medication,
no limitations on activity
Steps of Asthma management
- Short acting beta2-agonist inhaler
=> For all in whom asthma is suspected - Add inhaled low-dose ICS (e.g. beclomethasone, budesonide or fluticasone)
=> For all patients with CONFIRMED asthma
=> Remember steroids take 2-3 days to take effect. - Trial of LABA (e.g. Salmeterol)
- ALWAYS use LABA in combination with a steroid
- If no response from LABA, stop it and increase dose of ICS.
- If some response but more control required, continue LABA but increase ICS.
- Consider use of LTRA (e.g. montelukast), theophylline or a LAMA. - Increase dose of ICS (up to highest dose)
- Refer to specialist - Specialist management
- Can include oral steroids, oral beta2-agonists, biologics (e.g. omalizumab).
If salbutamol inhaler is used more than 2 times a week, this indicates that their current control is inadequate, and the care needs to move up a step.
What is important to remember when prescribing a LABA?
ALWAYS use LABA in combination with a steroid
Moderate Acute Asthma
Increasing symptoms
PEF 50-75%
NO features of acute severe asthma
Acute Severe Asthma Attack
Requires any one of:
* PEF 33-50% predicted best
* RR >25/min
* HR >110
* Inability to complete sentences in one breath
Life-threatening Asthma Attack
Any one of:
* PEF <33% predicted
* SpO2 <92%
* PO2 <8kPa
* Normal or RAISED PaCO2 (4.6-6)
* Silent chest
* Cyanosis
* Poor respiratory effort
* Arrhythmia
* Exhaustion
* Altered consciousness
* Hypotension
Asthma attack- Ix
If a patient has ANY life-threatening feature, an ABG is the only immediate investigation required whilst treatment is initiated.
Certain blood gas features are markers of a life-threatening attack:
=> Normal PaCO2 (should normally be low due to hyperventilation).
=> RAISED PaCO2 indicates near-fatal asthma.
=> Severe hypoxia <8 kPa
=> A low pH
Initial Emergency Tx of Asthma
- O2 to maintain sats at 94-98% (unless COPD) – usually 15L/min non-rebreather mask
- Salbutamol 5mg via O2 driven NEB
=> Add ipratropium to nebuliser if required - PO Prednisolone 50mg
=> Or IV hydrocortisone 100mg
If life-threatening features present:
- Discuss with senior and ICU
- Add IV magnesium sulphate 2g
- Keep giving nebulised salbutamol 5mg every 15-30 mins
- Senior clinicians may consider IV aminophylline or IPPV
Mx of patient post-asthma attack
If the patient is stable and improving:
- Continue prednisolone dose daily for at least 5 days.
- Continue nebulised salbutamol 4 hourly until discharge.
- Chart PEF before and after nebulisers, at least 4 times daily while in hospital.
Prior to discharge:
- Check inhaler technique
- Agree on written asthma action plan
- Ensure GP follow-up within 2 working days.
What is COPD?
= A disease of progressive airflow obstruction that is not fully reversible.
Associated with an abnormal inflammatory response of the lungs to noxious stimuli (predominantly [90%] cigarette smoke).
Encompasses a spectrum of illnesses:
1. chronic bronchitis – increased mucous, airway obstruction and intercurrent infections
2. emphysema – destruction of alveoli.
What is emphysema?
= Dilation of any part of the respiratory acinus (the air spaces distal to the terminal bronchioles), with destructive changes in the alveolar walls.
Loss of connective tissue in the alveolar walls leads to a loss of elastic recoil of the lungs, leading to air entrapment in the lungs and inadequate ventilation
Centrilobular Emphysema
Changes are limited to the central part of the lobule, directly around the terminal bronchiole.
Normal alveoli elsewhere
Most common form – associated with smoking.
Pan-acinar emphysema
Leads to destruction and distension of the whole lobule.
Can happen in smokers, but more common in alpha1-antitrypsin deficiency
What is chronic bronchitis?
= Daily cough with sputum for at least 3 months per year
Primary abnormality seen is abnormal amounts of mucous, which causes plugging of the airway lumen.
Hypersecretion is associated with hypertrophy and hyperplasia of the bronchial mucous-secreting glands.
COPD - RFs
Cigarette smoke exposure!!!
Occupational toxins – e.g. coal dust
Alpha1-antitrypsin deficiency
Recurrent chest infections in childhood
Low socio-economic status
Asthma/atopy
COPD - Presentation
- Productive morning cough, following many years of “smokers cough”
- Increased frequency of LRTIs
- Slowly progressive dyspnoea
- Exacerbated in acute infective episodes
- Wheezing
- Respiratory failure
- Chronic right heart failure (occurs late).
COPD - O/E
MILD – widespread wheeze
SEVERE:
- Tachypnoea, possibly cyanosis and/or flapping tremor
- Hyperinflation, intercostal recession on inspiration, signs of respiratory distress.
- Raised JVP if right heart failure
- Poor chest expansion
- Hyper-resonant throughout, loss of cardiac/hepatic dullness
- Decreased breath sounds, prolonged expiratory phase, polyphonic wheeze.
Will there be clubbing in COPD?
Clubbing is NEVER present in pure COPD
“Pink Puffers”
Patients remain sensitive to CO2, thus keep a low CO2 and near-normal O2.
Tachypnoeic, tachycardic, using accessory muscles to increase ventilation.
Breathless but not cyanosed.
Very thin – large amounts of calories used to breathe.
Can progress to type 1 respiratory failure.
More emphysematous.
“Blue Bloaters”
Patients are insensitive to CO2.
Severe chronic bronchitis/COPD.
Not particularly breathless but are cyanosed and oedematous (cor pulmonale).
Blood gas will show type 2 respiratory failure (low oxygen, retaining CO2.
Oxygen should be given with care to these patients.
Diagnosis of COPD
There is no single diagnostic test for COPD – diagnosis can be clinical if there are typical Sx, in a person >35 in the presence of a risk factor.
Everyone suspected of COPD should then undergo post-bronchodilator spirometry, CXR, FBC.
COPD - CXR
Hyperinflation (>7 anterior and >11 posterior ribs)
Flattened hemidiaphragm
COPD - FBC
Can show
- Secondary polycythaemia
- Anaemia of chronic disease
Severity of COPD by spirometry
Stage 1 – FEV1 >80% predicted (clinical diagnosis); mild.
Stage 2 – FEV1 50-79% predicted; moderate.
Stage 3 – FEV1 30-49% predicted; severe.
Stage 4 – FEV1 <30% predicted; very severe.
COPD - ABG
- Normal in mild disease
- Developing to type 1/2 respiratory failure as disease progresses.
Stable COPD - Mx
Patient Education:
=> How to recognise an exacerbation early
=> Action plan/rescue medication (in patients with frequent exacerbations).
Lifestyle advice:
=> Diet, exercise, SMOKING CESSATION
Pneumococcal and Flu vaccination
Medical Mx
Initial Medical Mx options for stable COPD
Short-acting bronchodilators (SABA or SAMA) are 1st line
Further medications are added if ongoing symptoms are limiting QoL or persistent exacerbations.
=> If no features of asthma/steroid responsiveness:
- Add a long-acting beta-agonist (LABA) and muscarinic agonist (LAMA)
- Add inhaled corticosteroids if still symptomatic
- Remove ICS after 3 months if no improvement.
=> If features of asthma/steroid-responsiveness* are present => LABA + ICS.
What are features of asthma / steroid responsiveness in COPD patients?
Previous diagnosis of asthma/atopy,
Blood eosinophilia,
Substantial variation in FEV1 over time or diurnally.
What Tx may be considered by specialists for COPD
Pulmonary rehabilitation
Oral aminophylline/theophylline
Mucolytics – e.g. carbocysteine
Roflumilast – PDE4 inhibitor
Nutritional supplements – consider for those with low BMI
Long-term oxygen therapy
=> Remember to warn patient not to smoke.
Surgery
Acute exacerbation of COPD - presentation
Dyspnoea and wheeze become worse
Increased production / change in colour or smell of sputum.
When is hospital admission considered in acute exacerbation of COPD?
- Severe breathlessness
- Rapid symptom onset
- Acute confusion
- Cyanosis
- Low O2 sats (<90%)
- Worsening peripheral oedema
Outpatient Mx of acute exacerbaton of COPD
Increase dose/frequency of SABA (using a spacer if they don’t already use one)
Prescribe 30mg prednisolone for 7-14 days for breathlessness interfering with regular activities.
Prescribe oral ABX on local ABX prescribing guidelines.
Safety net and follow-up in 6 weeks to optimise medical Tx.
Inpatient Mx of acute exacerbation of COPD
O2 should be titrated according to the patient’s alert card
If unknown patient, titrate saturations to 88-92% using a venturi system.
=> Start on a 28% mask at 4L/min
Mx as per outpatient regime, with targeted oxygen therapy and regular monitoring.
What is the definition of pneumonia?
= signs of infection of the pulmonary parenchyma, PLUS new shadowing on CXR (separates it from bronchitis).
CAP definition
- Clinical lower respiratory tract infection AND
- New pneumonic changes on CXR AND
- Onset of symptoms in the community OR within 48 hours of hospital admission.
CAP - Presentation
Acute systemic illness – fever/ rigors / vomiting
Cough
=> Initially short, dry and painful
=> Progresses to productive with mucopurulent sputum.
Dyspnoea
Pleuritic chest pain
=> May be referred to shoulder to anterior abdominal wall.
Elderly populations may report very few Sx but be very unwell.
CAP - O/E
Inspection
=> Tachypnoea
Palpation
=> Decreased chest expansion on affected side
Percussion
=> Dullness over affected area
Auscultation
=> Coarse crackles and pleural rub over affected area
=> Bronchial breathing
=> Increased vocal resonance => “99” heard better due to consolidation.
CAP - bacterial causes
CONVENTIONAL
S. pneumoniae
H. influenzae
ATYPICAL
Mycoplasma pneumoniae
Chlamydia pneumoniae
Legionella pneumophila
CAP - Ix
STANDARD:
Observations (including O2 sats)
Bloods – FBC, U&E, CRP, LFTs
=> Consider ABG
=> May need blood cultures.
Confirm diagnosis – CXR
Sputum sample for MC&S (plus mycoplasma PCR if suspected)
Throat swab in viral transport medium if severe / suspected viral pneumonia.
EXTRA:
Urine for legionella/pneumococcal antigen if moderate/severe
=> Empirical Tx will not cover legionella
Serum mycoplasma IgM if suspected.
CURB-65 score
Criteria for severe CAP = CURB65:
Confusion – mini-mental test score of 8 or less (new)
Urea >7 mmol/L (new)
Respiratory Rate >30 breaths per minute
Blood Pressure – systolic BP <90 mmHg or diastolic BP <60 mmHg
65 or more years old
One point for each new finding.
Score 0-1 = low severity
Score 2 = moderate
Score 3 or more
Mx of CAP
Low-severity CAP (score 0 or 1):
- Outpatient care
- PO Amoxicillin
- Alternatives available in penicillin allergy/atypical organism
Moderate severity CAP (score 2):
- PO amoxicillin + clarithromycin
- Usually admit the patient.
Severe CAP (score > 2):
- Can be >20% mortality
- Requires admission to at least Level 1 unit or even HDU/ICU.
- IV co-amoxiclav + clarithromycin.
=> Penicillin allergy/MRSA suspicion – vancomycin and levofloxacin.
- Treatment for at least 10 days.
Aspiration Pneumonia
Aspiration of gastric contents leading to chemical inflammation and infection.
This does not always show on CXR – suspect it e.g. in someone who has a low GCS and evidence of vomiting (so at risk of aspirating).
If suspected can add metronidazole for HAP or CAP – this is to cover anaerobic bacteria.
HAP Definition
- Clinical lower respiratory tract infection AND
- New pneumonic changes on CXR AND
- onset of symptoms > 48 hours after admission OR admission in the last 7 days
HAP - typical causative pathogens
Enteric gram-negative bacilli – ~60% HAP cases.
=> Enterobacteriaceae (e.g. Klebsiella)
=> Pseudomonas spp.
Strep. pneumoniae
H. influenzae
Staph. aureus
Management of HAP
Assess MRSA risk factors
Assess HAP severity – no evidence-based guidelines => clinical decision
Mild HAP – oral doxycycline.
Severe HAP – IV Tazocin.
THESE PATIENTS SHOULD BE DISCUSSED WITH MICROBIOLOGY
Pneumonia Follow-up
Follow-up CXR at 6 weeks
=> to ensure resolution of consolidation => to assess for persistent abnormalities of the lung parenchyma.
Non-resolution => ?endobronchial obstruction as cause of pneumonia (e.g. lung cancer)
Potential complications of pneumonia
Sepsis
Lung abscess
Empyema – pus-filled collection in the pleural space.
=> Often develops from a parapneumonic effusion
Lung abscess/empyema can be suspected if there is a persistent swinging pyrexia and rising CRP despite treatment.
Bronchopneumonia
Primary infection centres around the bronchi, spreading to involve adjacent alveoli which become consolidated.
Initial consolidation is patchy (involves lobules), but if left untreated can involve whole lobes.
Lobar pneumonia
Organisms gain entry to distal air spaces rather than colonising bronchi, thus there is rapid spread of infection through alveolar air spaces.
Macroscopically, the whole lobe becomes consolidated and airless.
Causes of PTX
SPONTANEOUS PTX
=> Primary
=> Secondary
TRAUMATIC PTX
=> Penetrating trauma, rib fractures
IATROGENIC PTX
=> Lung biopsy, endoscopy, subclavian cannulation, positive pressure ventilation.
Primary PTX
Lung parenchyma otherwise normal;
Often occurs in tall, thin young men.
Secondary PTX
Underlying lung disease/abnormality – e.g. COPD, asthmatic, malignancy, CF.
PTX - symptoms
May be asymptomatic if small / primary (low index of suspicion required).
Sudden onset of unilateral pleuritic pain
Progressive dyspnoea
PTX - signs
May be few physical signs
Reduced expansion on affected side
Increased resonance to percussion on affected side
Decreased breath sounds and reduced vocal resonance on affected side
If TENSION PTX:
- Tracheal deviation away from affected side;
- Cyanosis
- Severe tachypnoea
- Tachycardia
- Hypotension
What is tension PTX?
= Medical Emergency
Air in the pleural space leading to cardiac compromise.
Arises due to a one-way valve system, allowing air entry into the pleural space during inspiration but no air exit during expiration.
This results in very high intrapleural pressure, deflating the lung and decreasing venous return to the heart (leads to circulatory collapse).
Tension PTX - Ix
Diagnosis is clinical (there is no time for imaging).
Tension PTX - Mx
- Call for help immediately.
- A-E
- Oxygen therapy
- Needle decompression with a cannula
=> 2nd intercostal space, midclavicular line with a 14g (orange) cannula.
=> After decompression, patient will require rapid insertion of a chest drain.
PTX - Diagnosis
Basic Hx and Examination
ABG – if signs of respiratory distress / chronic lung disease
Erect CXR = diagnostic
=> you should not be able to see the edge of the lung; if you can, there is likely to be a PTX.
Size of PTX
Estimating the size of a pneumothorax is important for management.
Estimation of size from a CXR is imperfect but most practical.
=> General rule is that a 2cm interpleural distance at the level of the hilum equates to a pneumothorax of 50% of the volume of the lung.
=> <2cm is a small pneumothorax and patient may not need treatment.
Management - Primary PTX
Rim of air <2cm and patient is not SoB/hypoxic:
=> Discharge, with interval CXR at 2 weeks
=> Safety net – return to hospital if become SoB
=> Advise to avoid strenuous exercise and quit smoking.
Rim of air >2cm
=> Attempt aspiration
=> If successful (<1cm residual rim of air), discharge as above.
=> If unsuccessful, will require chest drain.
Management - Secondary PTX
Rim of air <1cm
=> Give oxygen and admit for 24h observation
Rim of air 1-2cm
=> Attempt aspiration
=> Chest drain if <1cm residual rim of air.
Rim of air >2cm
=> Will require chest drain.
Advice for patient post-PTX
After PTX, air travel should be avoided for 6 weeks, and scuba-diving should be permanently avoided.
If there is recurrent PTX (>2 occasions) or PTX that does not resolve within 5 days of a chest drain, then surgery may be indicated.
Pleural Effusion
= a build-up of excess fluid (normal = 15 mL) found between the layers of the pleura
(i.e. outside the lungs and therefore different to pulmonary oedema).
different types of pleural effusion
Haemothorax = accumulation of blood, due to trauma.
Empyema/pyothorax = accumulation of pus, due to infection.
Chylothorax = accumulation of lymph, due to thoracic duct leakage.
Fluid effusion = fluid accumulation, can be transudative or exudative
pleural effusion - TRANSUDATE
= Protein concentration <30 g/L
Occur due to increased hydrostatic pressure or decreased oncotic pressure.
CAUSES:
* Organ failure – Cardiac, Liver, Renal
* Peritoneal Dialysis
* Hypothyroidism
* Ovarian tumours
More often bilateral
pleural effusion - EXUDATE
= Protein concentration >30 g/L
Causes:
* Infections – bacterial pneumonia, TB
* Neoplasm – lung primary/secondary, mesothelioma.
* Pulmonary Embolism
* Autoimmune disease – RA/SLE
* Abdominal disease – pancreatitis, subphrenic abscess.
More often unilateral
Pleural Effusion - O/E
Decreased chest expansion
Tracheal deviation away (if large)
Dull percussion – due to underlying fluid
Decreased breath sounds
Can be bronchial breathing above effusion due to compression of lung
Reduced vocal resonance
Examination should also focus on features of possible cause – e.g. signs of liver/kidney disease, malignancy. Cardiac failure, RA/SLE, etc.
What can cause empyema?
caused by bacterial invasion of the pleural space
either from an adjacent pneumonia or from direct inoculation (e.g. poor aseptic technique in a chest drain).
Empyema - presentation, Ix, Mx
Clinically presents as fever plus signs of pleural effusion
Aspirated fluid is yellow and turbid, with pH <7.2, low glucose, high LDH
Require IV ABX and chest drain
Pleural Effusion - Ix
CXR
=> On Erect PA/AP, >300mL fluid is typically needed before effusion becomes evident.
USS
=> Can detect smaller amounts of fluid than CXR
=> Recommended to guide aspiration
Aspiration:
=> Fluid sent for MC&S, clinical chemistry (protein, LDH, glucose) and cytology
=> Also run through blood gas machine to determine pH.
Transudate vs Exudate
Transudate vs Exudate is determined by protein level, but if protein level is borderline (25-35 g/L), one positive element of LIGHT’S CRITERIA will suggest an exudate:
- Pleural fluid protein/serum protein >0.5.
- Pleural fluid LDH/serum LDH >0.6.
- Pleural fluid LDH more than two-thirds the upper limit of normal serum LDH.
Pleural Effusion - Mx
If aspirated fluid is turbid/purulent (or if pH <7.2 this also suggests empyema):
=> Place chest drain
=> Consider IV ABX
Drainage should also take place if symptomatic
Manage the underlying cause of effusion
What are the 3 main acid-base buffer systems in the body?
- Intra- and extracellular buffers (rapid)
- Ventilation (rapid)
- Renal regulation of H+ and HCO3 (slower)
Steps for interpreting an ABG
- How is the patient?
- Assess oxygenation
- On air – PaO2 should be >10kPa
= On Oxygen – PaO2 should be ~10kPa less than the % inspired concentration. - Determine the pH
- <7.35 is acidaemic
- >7.45 is alkalaemic - Determine the respiratory component
- If acidaemic, is the PaCO2 >6? Respiratory acidosis
- If alkalaemic, is the PaCO2 <4.7? Respiratory alkalosis - Determine the metabolic component
- If acidaemic, is the HCO3- <22? Metabolic acidosis
- If alkalaemic, is the HCO3- >26? Metabolic alkalosis - Is there any evidence of compensation?
- Base excess
- Negative in metabolic acidosis
- Positive in metabolic alkalosis
Respiratory Acidosis - causes
- Central – e.g. drugs, stroke, infection
- Airway obstruction
- Parenchymal emphysema
- Neuromuscular
- Obesity
Respiratory Acidosis
= Decrease in gaseous exchange leading to retention of CO₂
COMPENSATION:
High pCO₂ leads to renal retention of bicarbonate to buffer excess H⁺
Compensation by the kidneys results in an increase in secretion of H⁺ over 3-5 days leading to increase in plasma bicarbonate level
Respiratory Alkalosis
Hyperventilation => excess exhalation of CO₂, resulting in low pCO₂ and thereby increased pH
Respiratory Alkalosis - causes
- Anxiety, Pain
- Hypoxia => Altitude, pneumonia, aspiration, severe anaemia
- Drugs – progesterone, salicylates
- Sepsis
Metabolic Acidosis
Results from the body producing too much acid or the kidneys failing to excrete enough H⁺.
COMPENSATION:
Initially this creates a decrease in bicarbonate as carbonic acid is produced to buffer the H⁺
The lungs compensate by hyperventilation and blowing of the CO₂
Metabolic Acidosis - causes
The anion gap can be used to differentiate causes:
Normal Gap = bicarbonate is being lost:
- GI loss (e.g. diarrhoea)
- Renal disease allowing loss.
High anion gap = increased production of acids
- Lactic acidocis
- DKA
- Drugs (e.g. NSAIDs)
Metabolic Alkalosis
Results from increased bicarbonate due to either decreased H⁺ concentration or a direct increase in bicarbonate.
Bicarbonate shift can occur from retention, an intracellular shift in H⁺ or by ingestion of large amounts of alkali (e.g. antacids).
COMPENSATION:
The lungs compensate by slower breathing to retain more CO₂
Metabolic Alkalosis - causes
Excess base – e.g. Ingestion
Loss of acid (Vomiting, NG suction)
Burns
Hyperaldosteronism
Hypokalaemia
Type I Respiratory Failure
PaO2 low (<8 kPa)
PaCO2 normal or low
T1RF occurs with diseases of the lung parenchyma
=> e.g. Pulmonary oedema, pneumonia, PE, COPD, ARDS
=> An asthma attack is initially type 1, with type 2 indicating a peri-arrest state
What is Type 2 Respiratory Failure?
What are the causes?
PaO2 low (<8 kPa)
PaCO2 high (>6 kPa)
INSUFFICIENT VENTILATION to excrete the volume of CO2 being produced by tissues
=> Severe pulmonary disease – asthma, COPD, pulmonary fibrosis, OSA
=> Reduced respiratory drive – CNS pathology, sedation
=> Thoracic wall disease – rib fractures (pain), kyphoscoliosis, flail chest
=> Neuromuscular disease – diaphragm paralysis, MG, Guillain-Barre, poliomyelitis
Hypercapnia - presentation
- Headache
- Tachycardia
- Bounding pulse
- CO2 retention flap
- Papilloedema
Features of acidosis:
- Kussmaul respiration – “air hunger”, giving deep and laboured breathing.
- CV dysfunction – acidosis is negatively ionotropic
- K+ abnormalities
- Cerebral dysfunction – confusion or coma.
T1RF - Mx
- Treat the underlying cause
- Give high-flow oxygen via a face mask.
- Consider assisted ventilation if PaO2 remains <8kPa (e.g. CPAP)
T2RF - Mx
Respiratory centre may be reliant on hypoxic drive – oxygen therapy should be given with care (starting at 24% O2) and rechecking ABG after 20 mins.
What is interstitial Lung Disease?
= generic term used to describe a number of conditions that affect the lung parenchyma.
Causes of Interstitial Lung Disease
EXOGENOUS STIMULI
- Occupational / environmental – asbestosis, silicosis, coal dust inhalation
- Drugs
- Hypersensitivity reactions – e.g. EAA, Bird Fancier’s Lung
- Infections – TB/fungal/viral infections
ENDOGENOUS STIMULI:
- Sarcoidosis
- RA
- CTDs – SLE, systemic sclerosis, Sjogren’s
IDIOPATHIC
- Idiopathic Pulmonary Fibrosis = most common cause of interstitial lung disease
What drugs can cause ILD?
nitrofurantoin,
amiodarone,
sulfasalazine,
methotrexate,
some anti-cancer chemotherapy drugs
Interstitial Lung Disease - Presentation
SYMPTOMS:
- dyspnoea on exertion
- non-productive cough.
O/E:
- Inspection – may be signs of respiratory distress
- Palpation – reduced expansion
- Percussion – normal (unless secondary pathology).
- Auscultation – bilateral, fine end-inspiratory crackles; sometimes expiratory wheeze.
May also be signs of decompensation – i.e. signs of pulmonary HTN and right heart failure.
Idiopathic Pulmonary Fibrosis
= most common cause of ILD
Aetiology unknown
Along with the dry cough and dyspnoea, patients will report malaise and weight loss, with arthralgia.
Hx should attempt to exclude occupational exposures and connective tissue diseases.
O/E – fine end-inspiratory crackles and also can be cyanosis and clubbing.
Complications:
- T2RF
- Pulmonary HTN
- Increased risk of lung cancer
General Ix for interstitial lung disease of unknown origin
BLOODS
– FBC, ANA/RF if suspecting CTDs
CXR
=> reduced lung volume, bilateral reticulo-nodular shadowing.
HIGH-RESOLUTION CT
– more sensitive, essential for diagnosis
=> “honeycombing” seen on CT
SPIROMETRY
– restrictive deficit, reduced gas exchange (DLCO)
Potential further Ix in interstitial lung disease
Bronchoalveolar lavage – may indicate disease activity in IFF/EAA
Lung biopsy (via bronchoscopy or surgical) – only if diagnosis is uncertain.
Prognosis of ILD
typically poor prognosis and limited Tx options
Long-term management of ILD
Lifestyle:
- Smoking cessation
- Healthy diet and regular exercise
Pneumococcal and Flu vaccines
Many cases will be unresponsive to Tx
There are some monoclonal antibodies used in IPF if the patient meets the criteria:
=> Pirfenidone, Nintedanib
20% respond to long courses of prednisolone, tapered down.
Some patients will be suitable for lung transplantation
Mx of acute exacerbation of ILD
- Oxygen: High flow nasal oxygen, NIV rarely indicated as usually T1RF
- Exclude treatable pathology
- Empirical antibiotics
- Enoxaparin if suspect PE
- High dose steroids
- Careful consideration of ICU vs palliation
Dyspepsia
Epigastric/upper abdo pain
Occurs following a meal
Central, no radiation
Worse with bending/lying down and when drinking hot liquids/alcohol
Improves with sitting upright and antacids.
Symptoms of GORD
- Dyspepsia
- Acid reflux
- Waterbrash
- Bad breath
- Bloating and belching
- Nausea and/or vomiting
- Odynophagia and/or dysphagia
There may be atypical chest pain due to distal oesophageal muscle spasm and a nocturnal cough/wheeze (giving asthma type symptoms).
RFs for GORD
- Hiatus Hernia
- Raised IAP (pregnancy / obesity)
- Large meals, eaten late at night
- Smoking
- High caffeine intake
- (High fatty food intake)
- Drugs
=> Anticholinergics, nitrates, TCAs, CCBs
GORD - potential complications
- Oesophageal ulcers – bleeding, pain, odynophagia.
- Oesophageal strictures – dysphagia, odynophagia.
=> Caused by repeated ulcers/inflammation - Barrett’s Oesophagus
- Oesophageal Cancer
Diagnosis of GORD
Diagnosis is usually based on symptoms and treated empirically
If there are any RED FLAG SYMPTOMS (ALARM55) – patient should be referred for endoscopy
Also refer if:
- Unsure of GORD diagnosis
- Symptoms are persistent, severe or unusual
- Not controlled by medication
- May benefit from surgery
GORD - Mx
- Lifestyle changes
- Medical Management
- 1st line = Antacids (e.g. magnesiums or aluminium hydroxide) +/- alginates (e.g. Gaviscon)
- 2nd line = H2RAs (e.g. Ranitidine) / PPIs for 4-8 weeks.
- If symptoms return after the initial course, then test for H. Pylori in primary care.
=> Need 2 weeks PPI-free before testing.
GORD - lifestyle changes
- Weight loss and smoking cessation
- Eat small and regular meals; >3h before bed.
- Avoid hot drinks/alcohol.
- Avoid drugs that exacerbate the condition/damage the mucosa (e.g. NSAIDs)
Barrett’s Oesophagus
In patients with long-standing reflux, the normal stratified squamous epithelium of the oesophagus undergoes metaplasia to glandular columnar epithelium.
Continued inflammation can lead to dysplasia and malignant changes (risk approx. 0.5% per patient per year).
The process of metaplasia is asymptomatic, but the patient will have Sx of GORD
Barrett’s Oesophagus - Ix
OGD – if present, it will be visible and biopsies can be taken
Normal oesophageal squamous mucosa => metaplastic columnar mucosa
Barrett’s Oesophagus - Mx
Regular endoscopic surveillance with biopsies to look for dysplasia/carcinoma in situ (which can be treated with endoscopic resection.
The risk of malignant change is ~0.5% per year.
Gastric Ulcers - features
Occur in older patients (>55)
Mainly on the lesser curve of the stomach
Pain is worse on eating
Pain relieved by antacids
May present with small bleed (iron deficiency anaemia) or major haemorrhage (haematemesis)
Duodenal Ulcers - Features
4x more common than gastric ulcers
90% located within 2cm of the pylorus.
Pain is at night and before meals.
Relieved by eating food/drinking milk.
May present with bleeding or perforation
Peptic Ulcers - RFs
H. pylori infection
Zollinger-Ellison Syndrome
=> Excessive acid secretion due to non-insulin secreting islet cell tumour of the pancreas, secreting gastrin-like hormone.
=> Often leads to extensive ulceration.
Drugs:
- Long-term NSAIDs
- Long-term / high-dose Corticosteroids
Increased ICP (Cushing ulcers)
Post severe burns (Curling ulcer)
Hepatic/renal failure
Smoking, alcohol, caffeine
Peptic Ulcer - presentation
Nearly 75% of patients are asymptomatic.
Symptoms can be:
- Burning epigastric pain
- Pain related to food intake.
=> Typically relieved by eating in duodenal ulcers, worse on eating in gastric ulcers. - Feeling of fullness, bloating or belching.
- Appetite changes
- Unexplained weight loss
- Haematemesis/melaena
- Nausea
- Severe abdominal pain (?perforation)
Peptic Ulcer - Ix
Urgent OGD (2WW) if fit the ALARM-55 criteria.
=> Multiple biopsies taken from rim/ base for (histology & H/pylori) as well as brushings (cytology).
No investigation required if <55 and no ALARM55 criteria:
- Lifestyle measures
- PPIs/H2RAs
If symptoms persist on Tx, investigate for H. pylori
If previous peptic ulcer, assume H. pylori and eradicate with “triple therapy”.
Surgery for Peptic ulcers
Generally now only reserved for disease complications:
=> Haemorrhage, perforation, strictures, malignant changes
Sometimes in patients who cannot tolerate medical therapy
H. Pylori Infection
Infection will cause:
- Gastritis (mainly in the gastric antrum)
- Increased acid secretion (due to neutralisation of acid) and abnormal mucous production, leading to epithelial damage.
H. pylori is also associated with duodenal ulcers.
H. Pylori - Ix
13C Urea Breath Test
Stool antigen test
Serum test (if its performance has been locally validated)
OGD – biopsies can be added to a urea solution with phenol red dye, and if H. pylori is present there will be a colour change to the urease.
13C Urea Breath Test for H Pylori
- Patient ingests 13C-labelled Urea.
- If H. pylori is present, the urease enzyme will metabolise this to 13CO2 which can be detected on the breath.
- This will become negative when H. pylori is eradicated (unlike stool/serum tests)
!!! The patient should not take ABX for 4 weeks or PPI for 2 weeks before testing, as these can cause a false negative !!!
H. Pylori - Mx
H. pylori eradication involves triple therapy:
=> PPI + 2 antibiotics for 7 days.
Omeprazole + clarithromycin + amoxicillin (metronidazole in penicillin allergy)
What is IBS?
= a relapsing functional bowel disorder, with no discernible structural or biochemical cause.
It is shown to have a negative impact on quality of life, but it is not associated with the development of serious pathology.
The mechanisms may be differences in the “brain-gut axis”, leading to increased visceral perception and decreased visceral pain threshold.
IBS - RFs
Stress and other psychological factors
Dietary triggers (alcohol, caffeine, spicy foods)
Enteric infection
IBS - Diagnosis
Diagnosis of IBS is made POSITIVELY on symptom-based diagnostic criteria
Consider the diagnosis if any of the following symptoms for AT LEAST 6 months:
- Abdominal pain, or
- Bloating, or
- Change in bowel habit.
Make a diagnosis of IBS if a person has abdominal pain which is either:
- Related to defecation, and/or
- Associated with altered stool frequency (increased or decreased), and/or
- Associated with altered stool form or appearance (hard, lumpy, loose, or watery)
AND at least 2 from the following:
- Altered passage of stool (straining, urgency, tenesmus)
- Abdominal bloating/ distension/ hardness
- Symptoms aggravated by eating
- Passage of rectal mucus
- Associated gynaecological, urinary symptoms, or back pain.
IBS - Ix
History to ensure there are no Red Flag symptoms.
=> E.g. unintentional weight loss, PR bleeding, FHx bowel/ovarian cancer, change in bowel habit >60, incontinence, having to frequently open bowels at night.
Examination:
- For signs of anaemia / masses
Bloods:
- CRP/ESR + faecal calprotectin to exclude IBD
- TTG/ anti-endomysial antibodies to exlcude coeliac disease
- FBC – any anaemia ?
In cases that meet the criteria for IBS, no further investigations are required.
IBS - Conservative Mx
Form a therapeutic alliance and self-help materials
Lifestyle:
- Regular exercise
- Regular mealtimes, lots of water, limit tea/coffee, limit high insoluble fibre intake.
- Relaxation techniques.
Further dietary advice may be given by a dietician if initial measures are unsuccessful (i.e. low FODMAP diet).
Peppermint oil
IBS - Medical Mx
1st Line Medical Mx:
=> Antispasmodics (e.g. mebeverine) as 1st line medical Mx
=> Laxatives can be given for constipation
- But AVOID lactulose (bloating)
=> Loperamide is 1st choice anti-motolity agent for diarrhoea.
Further Medical Mx:
=> 2nd Line = Low dose TCAs once nightly.
=> 3rd Line = SSRIs, if TCAs are unsuccessful
Refractory IBS
defined as symptoms persisting after 12 months of antidepressant medications.
At this stage, referral for CBT may be made
pathophysiology of cirrhosis
- Destruction of Liver Cells
- Associated chronic inflammation, stimulating fibrosis
- Regeneration of hepatocytes to form nodules.
=> nodules lack normal vascular and bile drainage connections
Micronodular Cirrhosis
Nodules <3mm
occurs as a result of alcoholic liver disease or biliary tract disease.
Macronodular Cirrhosis
Nodules >3mm
occurs due to previous hepatitis
Causes of Cirrhosis
COMMON
* Alcoholic Liver Disease
* Cryptogenic Liver Disease (no cause found on investigation)
* Non-alcoholic Fatty Liver Disease (NAFLD)
* Chronic viral hepatitis
LESS COMMON
* Autoimmune hepatitis
* Primary biliary cirrhosis
* Primary sclerosing cholangitis
* Budd-Chiari Syndrome
* Cystic fibrosis
RARER
* Haemochromatosis
* Wilson’s disease
* Alpha-1 antitrypsin deficiency
What is Primary Biliary Cirrhosis?
= Autoimmune destruction of the intra-hepatic bile canaliculi
Occurs mainly in 40-60 year old females (90%)
Related to IBD
Often presents with jaundice, pruritis, skin xanthomas
It is a slowly progressive condition
Replacement of fat-soluble vitamins is important in Mx.
Primary biliary cirrhosis - Dx
Raised anti-mitochondrial antibodies (AMA) is considered diagnostic.
What is Primary Sclerosing Cholangitis?
What is the treatment?
= Autoimmune inflammation and fibrosis around the bile ducts in the liver.
This leads to secondary cirrhosis, due to chronic biliary obstruction.
70% associated with IBD
Cholangiocarcinoma can develop
No effective Tx other than transplantation
What is Wilson’s Disease?
= Rare inborn error of copper metabolism, leading to deposition of copper in many organs.
Classically the liver, basal ganglia and cornea (Kayser-Fleischer rings)
It is treatable, so any person with hepatic/neurological problems should be screened.
Wilson’s Disease - Ix and Mx
Ix:
- Serum caeruloplasmin (reduced), urinary copper (increased)
- Liver biopsy shows increased copper
Tx = chelating agents (e.g. D-penicillamine or trientene).
What is Haemochromatosis ?
What is the classic presentation?
= Inherited condition characterised by excess iron deposition in various organs, leading to fibrosis and organ failure.
Classic triad (only present in gross overload):
- Bronze skin discoloration
- Hepatomegaly
- DM
Hypogonadism is a common presenting feature (impotence, testicular atrophy) due to pituitary iron deposition).
Haemochromatosis - Ix and Mx
Ix:
- Serum iron/ferritin (both raised)
- Total iron binding capacity decreased
- Genetic testing
- Liver biopsy
Tx:
=> Venesection (1 unit per week initially until iron levels are normal, then 2-4 times per year; usually lifelong).
Classic History in chronic liver disease
Fatigue
Weight loss/anorexia
- Early satiety with hepatomegaly
- BUT Patient may often note “central weight gain” of ascites.
Jaundice
Leg swelling
=> Due to decreased oncotic pressure and increased intra-abdominal pressure)
Bleeding/bruising
=> Due to decreased synthetic function)
Itching
=> Due to bile salt accumulation in peripheral nerves
=> Tx = cholestyramine
Signs of chronic liver disease O/E
Nails
=> Leukonychia due to low albumin
=> Clubbing
Hands:
=> Palmar erythema
=> Dupytren’s Contracture
=> Liver flap
Skin:
=> Pigmentation / jaundice
=> Spider naevi
=> Striae
Feminisation:
=> Gynaecomastia, testicular atrophy and loss of body hair
Signs of portal HTN:
=> Caput medusae
=> Hepatosplenomegaly
=> Ascites
Signs of hepatocellular failure:
=> Bruising
=> Prolonged clotting
Why can chronic liver disease lead to signs of feminisation?
Secondary hyperaldosteronism (due to activation of RAAS because hypoalbuminaemia leads to a lower circulating volume)
What can precipitate decompensation of chronic liver disease?
- Alcohol binge
- Variceal bleed
- Hepatotoxic drugs
- Portal/hepatic vein thrombosis
Child-Pugh score
Gives prognosis for patients with chronic liver disease
Uses variables:
A - albumin
B - bilirubin
C - clotting (INR / PTT)
D - distention (ascites)
E - encephalopathy
Chronic Liver Disease - Ix
Liver function – albumin & INR are the best indicators
Liver damage – LFTs
Complications:
=> U&Es (hepatorenal syndrome) / ABG (hepatopulmonary syndrome).
LIVER SCREEN to find cause:
- Viral serology
- Serum autoantibodies/Ig
- AFP
- Iron studies (hereditary haemochromatosis)
- Serum copper/caeruloplasmin (Wilson’s disease)
- Alpha1-antitrypsin level
IMAGING:
- USS & duplex of liver and abdomen.
- Endoscopy – detection and Tx of any varices; should be undertaken in anyone with suspected cirrhosis.
- MRI if indicated
Further Ix:
- Ascitic Tap
- Liver biopsy (gold-standard, but not always required)
When is an OGD indicated in cirrhosis?
should be undertaken in anyone with suspected cirrhosis.
for detection and Tx of any varices (as 90% of cirrhosis patients develop these)
Cirrhosis - Mx
Tx depends on the patient, and cause, severity, and complications
May include:
* Avoidance of alcohol
* Laxatives to maintain bowel movements, ideally >2 per day
* Good nutrition and advice from a specialist dietician
* Avoidance of drugs that cause hepatic impairment
The ONLY definitive treatment is liver transplant (if suitable, depending on cause).
=> However, there is a shortage of donated livers available.
Ascites - presentation and Mx
= fluid in the peritoneal cavity, which can accumulate slowly or rapidly.
Mild abdo pain is common
=> If severe pain, consider spontaneous bacterial peritonitis.
Mx =
- Initially bed rest, fluid restriction, low-salt diet and spironolactone
- Ideally the patient should lose 0.5-1kg in 24 hours.
- Furosemide can be added if the response is poor
- Therapeutic paracenteses and albumin infusion reserved for large volume ascites.
Suspected spontaneous bacterial Peritonitis - Mx
suspected if ascites with fever, pain, deterioration
=> Ceftriaxone IV until sensitivities are known (diagnostic tap)
=> Long-term norfloxacin (as recurrence is high).
Hepatic Encephalopathy - cause and severity
Caused by nitrogenous waste build-up in the circulation.
Leads to cerebral oedema when astrocytes attempt to clear it.
Severity:
- Grade I – altered mood/behaviour, sleep disturbances
- Grade II – increasing drowsiness and confusion
- Grade III – stupor, incoherence, restlessness
- Grade IV – Coma
Hepatic Encephalopathy - Mx
ICU admission with 20 degree head tilt
Oral lactulose, with regular enemas to clear the bowel of nitrogen-forming organisms
If there is evidence of cerebral oedema, IV mannitol and hyperventilation may be used.
Where are there Porto-systemic anastomoses ?
Cardia of the stomach => gastric/oesophageal varices
Anus => rectal varices
Retroperitoneal organs => stromal varices
Paraumbilical veins of anterior abdominal wall => caput medusae.
When portal blood flow is obstructed, blood from the portal territory is able to use these collateral routes to return to the heart (as the portal system has no valves, so blood can flow in a reverse direction).
What is portal HTN?
= pressure in the portal vein >10mmHg (normal = 5-10 mmHg)
Causes of portal HTN
PRE / POST-HEPATIC
Portal vein thrombosis (Budd-chiari syndrome)
HEPATIC
Cirrhosis
Hepatitis
Idiopathic non-cirrhotic portal HTN
Schistosomiasis
Congenital hepatic fibrosis
What is Budd-Chiari Syndrome?
= obstruction of hepatic veins, most commonly due to thrombosis or obstruction due to external mass
Portal HTN - manifestations
Variceal Bleeding
Haemorrhoids/caput medusae
Ascites
Splenomegaly
Porto-systemic encephalopathy (toxins bypass liver).
What is Unstable Angina ?
What is the pathology?
(also “crescendo angina”)
= Angina occurring at rest, or sudden increased frequency/severity of existing angina.
Pathologically caused by fissuring of atheromatous plaques, this there is a risk of subsequent total vessel occlusion and progression to MI.
Regional MI
Infarct of one segment of the ventricular wall
Nearly always due to thrombus formation on an atheromatous plaque, giving prolonged ischaemia.
The area of regional infarction depends on the artery occluded.
Regional Subendocardial Infarction
If there is lysis of the thrombus, or a strong collateral supply, the infarct is limited to the subendocardial zone (the most distal point from the blood supply).
Circumferential subendocardial Infarction
Caused by general hypoperfusion of all coronary arteries, usually due to hypotensive episode in arteries already affected by high-grade atherosclerosis.
What is required for a diagnosis of MI?
The diagnosis of MI requires elevations in serum cardiac troponin levels (i.e. cardiac myocyte death)
Additional categorisation based on ECG:
=> ST elevation / new LBBB = STEMI
=> No ST elevation/LBBB = NSTEMI
STEMI vs NSTEMI
STEMI generally correlates with a full-thickness MI
NSTEMI is often a partial-thickness lesion.
MI - RCA
Supplies RA, RV, posterior septum
Gives posterior/inferior MI
=> Leads II, III, aVF
Also supplies the AVN in 80% and SAN in 60%
MI - LCA
Splits into the circumflex and left anterior descending artery.
Gives a massive antero-lateral MI.
=> Leads I, aVL, and V1-V6
MI - circumflex artery
Mainly supplies LA and LV
Gives lateral MI
=> Leads I, aVL, V5 & V6
MI - left anterior descending artery
Mainly supplies the LV and anterior septum
Gives antero-septal MI
=> Leads V1-V4
ECG - lateral region
I
aVL
V5
V6
ECG - inferior region
II
III
aVF
ECG - anterior region
V1
V2
V3
V4
End pathophysiology of MI
The end result is replacement of the necrotic area with collagenous scar, which occurs in a predictable time-course
- 12-24 hours – infarct pale and blotchy, with intercellular oedema
- 24-72 hours – infarcted area excites acute inflammatory response, with dead area soft and yellow with neutrophilic infiltration.
- 10 days to several months – collagen deposition, infarct replaced by collagenous scar
ACS - Symptoms
Severe crushing, gripping or heavy chest pain lasting longer than 20 minutes.
- Not relieved by 3x GTN sprays at 5 minute intervals.
Radiates to the left arm, neck or jaw.
Associated with dyspnoea, nausea, fatigue, sweatiness and palpitations, with distress and a feeling of “impending doom”.
“Silent” MI
MI without chest pain
More common in the elderly and diabetics
MI - O/E
Sympathetic activation – tachycardia, HTN, pallor, sweatiness.
Vagal stimulation – bradycardia, vomiting.
Myocardial impairment – hypotension, narrow pulse pressure, raised JVP, basal crepitations, 3rd heart sound.
Tissue damage – low-grade pyrexia
MI - later signs
Pericardial rub = an extra heart sound due to friction
=> Resembles the sound of squeaky leather and often is described as grating, scratching, or rasping.
=> Best heard between the apex and sternum but may be widespread
Peripheral oedema
Pan-systolic murmur due to papillary muscle rupture/ventriculo-septal defect
MI - Ix
ECG = essential in all patients presenting with chest pain.
=> Repeated every 15 minutes whilst in pain, or continuous monitoring in ACS (due to high chance of arrythmias developing).
Bloods:
- FBC, U&E
- Glucose, lipids
- Cardiac Enzymes to confirm MI
CXR:
- Consider for evidence of cardiomegaly/ pulmonary oedema (heart failure), widened mediastinum (aortic dissection)
If Dx still in doubt => Transthoracic Echocardiography may confirm, or help detect alternative diagnoses.
Cardiac Enzymes in MI
Troponins are 1st Line:
- Rise 4-8 hours following onset of symptoms
- Peak at 24 hours
- Detectable for 10 days
(Also raised in critically unwell patients with non-cardiac causes)
Pattern of ECG wave morphology in STEMIs
a. At onset of pain – the ECG shows a normal sinus complex
b. Within 1 hour – noticeable ST segment elevation has developed
c. Following treatment – subsequently, T-wave inversion may develop
d. 24h later – ST segment has returned to baseline, T-wave inversion persists
e. Days/Months later – deep Q-wave indicating tissue death
=> A deep Q wave will remain on the ECG (i.e. if only pathological Q-waves are present, this could be from a previous MI).
Cardiac chest pain with new onset LBBB
can be assumed as a STEMI, as further interpretation of the ECG is not possible.
How can you differentiate unstable angina from MI?
In unstable angina:
There may be ischaemic ST depression in the leads affected,
There will be NO troponin rise (i.e. no infarction).
ACS - Immediate Mx
INFORMANT
INvestigations
=> ECG, Troponin, U&Es, glucose, Hb, ?angiography
=> If there is ST elevation on ECG, immediate referral to cardiology for PCI is required.
Fondaparinux
=> 2.5 mg SC OD for 2-8 days (until no chest pain for >24 hours)
Oxygen
=> Prescribe, but only indicated if SpO2 <94%
Reassurance
Morphine
=> 5-10mg by slow IV injection initially
=> Usually need to co-prescribe metoclopramide 10mg IV (unless contraindicated).
Aspirin
=> 300 mg PO; such or chew for faster absorption
Nitrate
=> Sublingual GTN (e.g. 400 mucrogram spray)
=> Consider IV infusion if pain continues
Ticagrelor
=> First dose = 180mg PO
=> Continues for 12 months at 90 mg bd
Mx of STEMI
Percutaneous Coronary Intervention (PCI) is gold-standard, if available in a timely fashion.
=> Door to balloon within 90 minutes.
PCI is contraindicated if there are significant co-morbidities
Thrombolysis is indicated in STEMI when PCI is contra-indicated
Mx of NSTEMI / UA
High risk – if GRACE mortality >3% in 6m, or raised troponins, persistent pain, ST depression, or diabetes.
=> Organise semi-elective PCI as an inpatient
Low Risk – i.e. resolved unstable angina or GRACE <3%
=> Potentially can be discharged with long-term medication and outpatient follow up.
ACS - long-term Mx
48 hour bed rest with continuous ECG monitoring
Daily U&Es and cardiac enzymes for 2-3 days
Thromboprophylaxis
=> Fondaparinux s.c. 2.5mg o.d. for max 8 days (until chest pain free for 24h)
DUAL ANTIPLATELET THERAPY
=> Aspirin 75mg o.d. continued for life
=> Ticagrelor OR clopidogrel for ONE YEAR
Bisoprolol for life, titrated to maximum tolerated dose.
ACEI titrated to maximum tolerated dose
Atorvastatin 80mg o.n.
GTN Spray for angina Sx
Address modifiable risk factors
Complications of MI
IMMEDIATE
Arrythmias - VT, VF, AF, bradycardia/block (if AVN/SAN affected)
SHORT-TERM
Pulmonary Oedema
Cardiogenic Shock
Thromboembolism
Ventriculo-septal defect
Ruptured chordae tendinae
Rupture of ventricular wall
LONG-TERM
Heart failure
Dressler’s Syndrome
Ventricular aneurysm formation
Dressler’s Syndrome
= Immune-mediated pericarditis; associated with high ESR and sometimes anti-myocardial antibodies.
Develops in a very small number of cases, 2-10 months after an MI.
Pericarditis gives sharp chest pain (different to that of MI), exacerbated by movement and lying down, relieved by sitting forwards.
O/E – classic pericardial friction rub at lower left sternal edge, with the patient leaning forwards.
Tx = high-dose aspirin/NSAIDs
It is important to recognise that pericarditis (non-immune mediated) can occur at any time following MI, and this is more common than Dressler’s syndrome.
=> Tx = opioids for pain.
Ventricular Aneurysm formation
Gradual Distension of the infarcted part of the ventricular wall, which has been replaced by collagen scar.
Aneurysmal rupture will lead to cardiac tamponade and death.
Rupture of Ventricular Wall
Usually occurs 2-10 days after the infarct, due to re-organisation and softening of the wall.
Leads to haemopericardium, cardiac tamponade and rapid death.
Causes of Heart Failure
Common Causes
1. IHD (most common)
2. Dilated cardiomyopathy
3. HTN
Rarer Causes
* Other cardiomyopathies
* Valvular Disease
* Congenital heart disease
* Cor pulmonale
* Alcohol / drugs
* AF / heart block
* Anaemia
What is Left Ventricular Heart Failure?
The left side of the heart must work harder to pump the same amount of blood.
Poor output of the impaired left ventricle leads to an increase in left atrial and pulmonary venous pressure.
=> causes pulmonary oedema, as the increased pulmonary venous pressure prevents the reuptake of fluid at the level of the capillaries.
What is Right Ventricular Heart Failure?
RV output fails.
Predominantly due to lung disease (cor pulmonale) and pulmonary valvular stenosis.
This typically leads to peripheral oedema.
What is Biventricular Failure?
LVF and RVF may be present at the same time, due to either:
i. Disease (e.g. IHD) affecting both sides of the heart
ii. LVF leading to pulmonary congestion which can then lead to RVF = “congestive heart failure”
LV Failure - Presentation
Symptoms:
- Fatigue
- Exertional dyspnoea, Paroxysmal nocturnal dyspnoea, Orthopnoea
Signs are often very few until late stages (unless failure is acute):
- Pulmonary oedema/congestion
- 3rd heart sound, plus “Gallop rhythm” if tachycardic.
- Cardiomegaly, laterally displaced apex beat.
RV Failure - Presentation
Symptoms:
- Fatigue
- Breathlessness
- Anorexia/nausea (due to hepatomegaly)
- Swollen Ankles
Signs tend to be more prominent than symptoms:
- Jugular venous distension
- Hepatomegaly
- Cardiomegaly
- Peripheral oedema
- Pleural effusions
- Ascites
Cardiac Cachexia
A syndrome of life-threatening weight loss due to a combination of:
- Hepatomegaly (nausea and anorexia)
- Increased metabolic demands
Maladaptive compensatory mechanisms in cardiac failure
- Reduced CO leads to activation of the SNS and RAAS.
- RAAS activation leads to vasoconstriction (increasing afterload) and sodium/water retention (increasing preload) thus further increasing BP and cardiac work.
- SNS activation initially maintains cardiac output by increasing contractility, yet prolonged stimulation leads to myocyte apoptosis and necrosis.
Adaptive mechanisms in cardiac failure
Atrial Natriuretic Peptide (ANP) is released in response to atrial stretch, and acts to antagonise the fluid-conserving effects of aldosterone.
New York Heart Association (NYHA) Classification of Heart Failure
Class I
Disease present, but no limitation of physical activity.
Class II
Dyspnoea present on ordinary activities
Class III
Marked limitation of activity (breathlessness with minimal exercise)
Class IV
Dyspnoea present at rest, any activity causes discomfort.
Cardiac Failure - Ix
Bloods:
- FBC, LFT, U&Es, TFTs
- Cardiac enzymes in acute failure
B-type natriuretic peptide (BNP)
=> Normal level will exclude heart failure, so a good screen for breathlessness in GP
CXR:
=> Cardiomegaly and pulmonary oedema.
ECG:
=> For signs of ischaemia, hypertension or arrythmias.
Echo = gold standard for diagnosis.
=> EF <45% is diagnostic
Management of CCF
Upon confirmed diagnosis of LV dysfunction:
- Lifestyle advice
- ACEi and beta-blocker are 1st line
=> Proven mortality benefit in heart failure! - Add diuretic if symptomatic oedema
- Aldosterone antagonists (e.g. spironolactone) / ARB / hydrasalazine plus nitrate = 2nd line.
- Cardiac resynchronisation therapy / digoxin / ivabradine = 3rd line
Heart failure - lifestyle advice
Patient education
Weight control
Dietary modification (fluid and salt restriction in severe heart failure)
Smoking cessation
Physical Activity:
=> Bedrest is important following an exacerbation
=> Low level endurance exercise is recommended in all patients with compensated heart-failure.
Vaccination – against pneumococcal disease and flu.
Sex – patients should not take Viagra.
ACEIs in heart failure
Work to reverse the neurohormonal adaptation in CHF.
Low dose used and titrated upwards.
Beta-blockers in heart failure
Used to block the SNS activity causing maladaptation.
Also anti-arrhythmic effects.
By reducing sympathetic drive, the symptoms initially become worse!
=> WARN THE PATIENT!!!
=> Low dose and then titrate up.
Diuretics in heart failure
Mainly used for symptomatic relief of oedema, but also venodilate.
Thiazides (Bendroflumethiazide) are used in mild failure or in elderly patients, where massive diuresis may be intolerable.
Loop diuretics (furosemide) are used especially in pulmonary oedema.
Both types can cause hypokalaemia (thus can be useful to counteract the hyperkalaemia from ACEi)
Spironolactone = potassium-sparing diuretic
=> Used at low (non-diuretic) dose of 25mg to reverse the neurohormonal adaptation
Digoxin in heart failure
Used in refractory heart failure.
Positive ionotrope and negative chronotrope
=> increases force of contraction but decreased heart rate.
Impairs AVN conduction and also increases vagal activity.
Contra-indicated in heart block and bradycardia.
DOSING:
- Dosage is according to eGFR (drug is 2/3rds renally cleared).
- Dosage titrated to make sure HR does not fall below 60 bpm.
NARROW THERAPEUTIC WINDOW
=> toxicity suggested by anorexia, nausea, visual disturbances, diarrhoea.
Renal function in heart failure
Always monitor renal function in patients being treated for heart failure:
- Digoxin is renally cleared
- Thiazides are ineffective in renal failure
- ACEis are used with caution in renal failure
- Diuretics and ACEis can lead to hyperkalaemia.
Acute Heart Failure - Mx
Sit the patient up and give high flow oxygen
IV Furosemide 40-80mg
GTN spray 2 puffs SL (unless SBP <90)
Continue with necessary history and investigations
If SBP >100 – start IV infusion of nitrate
=> Consider NIV (e.g. CPAP) if not improving
If SBP <100 – treat as cardiogenic shock, alert ICU
=> May require invasive ventilation
What is angina?
episodic pain that takes place when there is increased myocardial demand (usually upon exercise), in the presence of impaired perfusion by blood.
Causes of myocardial ischaemia
REDUCED PERFUSION – atheroma, embolus, thrombosis, spasm or inflammation of coronary arteries, generalised hypotension.
REDUCED BLOOD OXYGENATION – anaemia, carboxyhaemoglobinaemia
INCREASED TISSUE DEMANDS – increased CO2, cardiac hypertrophy.
Arteriosclerosis
Non-specific thickening and hardening of the walls of arteries, causing a loss of contractility and elasticity and decreased blood flow.
Often due to prolonged HTN in smaller arteries
pathophysiology of atheroma formation
Damage to the endothelium due to a variety of RFs => allows entry of LDLs into the intima.
The lipid is taken up by macrophages in the intima, and accumulates excessively as it is able to bypass normal receptor mediated uptake, forming a “fatty streak”
As the macrophages take up more and more lipid, they release free lipid into the intima.
The macrophages also stimulate cytokines, which lead to collagen deposition by inflammatory cells and the intimal lipid plaque becomes fibrotic.
At this stage it appears raised and yellow, and leads to pressure atrophy of the media an disruption of the elastic lamina.
Increased secretion of collagen forms a dense fibrous cap to the plaque, which is now hard and white.
Advanced plaques also show free lipid as well as lipid in macrophages
The endothelium is fragile and often ulcerates, allowing platelet aggregation.
Stable Angina - Sx
Ischaemic pain of the myocardium
=> Varying from a mild ache to a severe pain that provokes sweating and fear
Pain provoked by exercise
=> Especially after meals, in the cold, and if the patient is angry/excited.
Pain fades quickly with rest / GTN
In some, the pain occurs predictably at certain levels of exertion.
May be some associated SoB
Stable Angina - O/E
Usually no abnormal findings O/E
Occasionally a 4th heart sound
BP should always be taken
What are some variants of stable angina?
- Decubitus angina
- Variant / Prinzmetal’s Angina
Decubitus angina
angina precipitated by lying down (as there is increased venous return to the heart)
=> Associated with LVF
Variant / Prinzmetal’s Angina
occurs without provocation at rest, as a result of coronary artery spasm
=> There is ST elevation during the episode, so consider if ST elevation but no troponin rise.
Angina - Ix
Clinical assessment alone can be sufficient to confirm stable angina.
Exclude other causes
=> FBC, glucose, lipids, TFTs
Resting 12-lead ECG – usually normal, may be signs of previous infarction
=> Consider aortic stenosis if LVH / LBBB
Consider stress 12-lead ECG
Then use clinical assessment and ECG findings to estimate the likelihood of coronary artery disease using the NICE tool.
Stress 12-lead ECG
if resting ECG is normal, use Bruce protocol on treadmill, with ST depression >1mm indicating ischaemia.
=> If positive within 6 minutes then angiography indicated (only 70% sensitive).
Stable Angina - Mx
Education & lifestyle advice:
- Explain diagnosis
- Inform that the disease has a good prognosis
- Healthy balanced diet, weight loss if necessary
- Reduce alcohol, smoking cessation
Treat underlying problems and co-morbidities
Symptomatic Tx:
- SL GTN Spray = 1st line for relief
- Add beta-blocker OR RL CCB to reduce symptoms
- 2nd line = combination therapy (beta-blocker and NON-RATE LIMITING CCB) or Nicorandil
Secondary Prevention:
- Consider Statin (if QRISK high)
- Consider low-dose aspirin (75mg o.d.)
Refer to cardiology if any doubt over the diagnosis, atypical features or refractory symptoms.
How should patients with angina be advised to use their GTN spray?
Patients should be advised to:
- Sit down, rest and spray once beneath the tongue
- Wait for 5 mins
- Spray again if there is still pain
- If there is still pain at 10 minutes, call 999 and unlock the door
They can also be used prior to performing activities that will provoke angina.
How do nitrates work in managing angina?
Nitrates cause marked venorelaxation, thus REDUCES pre-load and afterload, and INCREASES coronary artery dilation.
=> decreases the oxygen requirement of the myocardium, and coronary vasodilation leads to increased oxygen delivery.
(Nitrates also relieve the coronary artery spasm of Prinzmetal angina. )
How do beta-blockers work in angina?
beta1 selective blockers are used to reduce cardiac rate and force (this reduces myocardial oxygen consumption), with as little broncho-constrictive effect as possible.
They also have anti-arrhythmic effects (class II)
How do CCBs work in angina?
Both types work to prevent smooth muscle contraction, reducing afterload and causing coronary vasodilatation.
The rate-limiting agents also act on cardiac calcium channels in the AVN to control the heart rate, exhibiting class IV anti-arrhythmic effects
CCBs are 1st line in Prinzmetal angina
Common SEs of CCBs
Flushing and headache (as with all vasodilators)
Ankle swelling
Constipation
In what conditions are murmurs of each valve area heard best?
Mitral
= Patient on their left hand side
Aortic
= Patient leaning forward, breath held in expiration
Pulmonary
= Breath held in inspiration
Tricuspid
= Breath held in inspiration
Mitral Stenosis - causes
Post-inflammatory scarring (history of rheumatic fever in >50%)
Mitral stenosis - pathophysiology
- The LA is unable to empty, leading to pulmonary HTN.
- The LA becomes dilated and hypertrophied
- Pulmonary HTN leads to RHF
- AF commonly develops due to muscular hypertrophy.
Mitral Stenosis - Sx
Dyspnoea & haemoptysis – pulmonary HTN
Fatigue, weakness, abdominal / LL oedema – RHF
Palpitations – secondary AF
Mitral Stenosis - O/E
Inspection:
* Malar flush – due to vascular stasis
* Small volume regular pulse (or irregularly irregular in AF)
* Raised JVP
Palpation:
* Left parasternal heave, due to RV hypertrophy (aka right ventricular heave).
Auscultation:
* “Rumbling” mid-diastolic murmur, loudest at the apex, just prior to systole.
* Also a loud S1, and “opening snap”
Mitral stenosis - Mx
Treat AF appropriately
Diuretics – reduces pre-load & pulmonary venous congestion
Surgical Mx => If medical measures fail (symptoms still limiting activity)
- Balloon valvuloplasty if valve pliable / non-calcified
- Open valvotomy.
Mitral Regurgitation - Causes
Post-inflammatory scarring – commonly rheumatic
Post-infarction papillary muscle dysfunction
LV dilation – i.e. in LVF, hypertrophic cardiomyopathy
Mitral prolapse
Mitral Regurgitation - O/E
Inspection:
* Signs of LHF/RHF develop in later disease
* AF can also develop (but less common than in mitral stenosis)
Palpation:
* Laterally displaced apex beat
* Systolic thrill
Auscultation:
* Pansystolic murmur at the apex, radiating to the axilla.
* Soft S1
* Prominent third heart sound (due to sudden rush of blood into dilated LV in diastole if decompensated).
Mitral Regurgitation - Mx
Treat AF
Treat Heart failure
Surgery if Sx are deteriorating to prevent irreversible LV impairment
=> Generally considered at NYHA grade 2
Aortic Stenosis - causes
Calcification of congenital bicuspid valve
Post-inflammatory scarring – rheumatic fever
Senile calcific degeneration – no known cause
Aortic Stenosis - pathophysiology
Progressive outflow obstruction leads to LV hypertrophy, which may lead to angina.
There is a risk of sudden cardiac death due to arrythmias
Without surgical intervention prognosis is poor with death in 2-3 years.
Aortic Stenosis - Sx
Exercise induced syncope
Angina
Dyspnoea
Aortic Stenosis - O/E
Inspection:
* Small pulse volume, slow rising carotid pulse
* Narrow pulse pressure (e.g. 110/95) as stroke volume small
* Signs of LVF then CCF
Palpation:
* Normal apex beat
* May be systolic thrill in aortic area
Auscultation:
* Ejection systolic murmur with a crescendo-decrescendo characteristic.
* Best heard in the aortic valve area
* Can radiate to carotids
* S2 is soft
Aortic Stenosis - Mx
Prompt valve replacement if symptomatic
Percutaneous valvuloplasty if unfit for surgery.
Aortic Regurgitation - causes
- Post-inflammatory scarring
- Infective endocarditis
- Age-related calcification
- Dilation of the aortic root
Aortic Regurgitation - Sx
Usually asymptomatic until acute left ventricular failure.
Symptoms may include angina (due to low diastolic BP) and dyspnoea.
Aortic Regurgitation - O/E
Inspection:
* Bounding/collapsing pulse
* Wide pulse pressure (e.g. 140/40)
* Signs of LVF
Auscultation:
* Early diastolic murmur with a “decrescendo” quality.
Specific Signs in severe disease:
* Quinke’s sign – capillary pulsation in nail beds
* De Musset’s sign – head nodding with each heartbeat
* Duroziez’s sign – murmur on the femoral arteries if pressure applied distally.
* Pistol shot femorals – sharp bang in time with the heartbeat if femorals auscultated.
Aortic Regurgitation - Mx
Aim to replace valve before there is significant LV dysfunction (indicated if there are increasing Sx, cardiomegaly, ECG deterioration).
Tricuspid Valve Disease - signs
STENOSIS
- Symptoms of RHF
- Signs of pre-systolic liver thrill and mid-diastolic murmur.
REGURGITATION
- Symptoms of RHF
- Signs of systolic liver thrill and pan-systolic murmur.
- Classic in cor pulmonale.
Pulmonary Valve Disease
STENOSIS
- Symptoms of RHF
- Signs of RV heave and ejection systolic murmur
REGURGITATION:
- Usually asymptomatic, with a diastolic murmur.
- Can occur secondary to pulmonary HTN
Systolic Murmurs
Aortic Stenosis
Mitral Regurgitation
Pulmonary Stenosis
Tricuspid Regurgitation
VSD/ASD
Diastolic Murmurs
Aortic Regurgitation
Mitral Stenosis
Pulmonary regurgitation
Continuous murmurs
= continuous throughout systole and diastole
Patent Ductus Arteriosus
Eisenmenger’s Syndrome - causes
occurs when there is a right to left shunt across a structural heart lesion, bypassing the lungs.
Occurs due to VSD, ASD or PDA
=> Can develop after 1-2 years with large defects or in adulthood with small defects.
Eisenmenger’s Syndrome - pathophysiology
Initially left-to-right shunt as pressure is higher in LV => blood still travels to the lungs
Over time the extra blood flowing into the right side of the heart and the lungs increases the pressure in the pulmonary vessels.
=> PULMONARY HTN.
When the pulmonary pressure exceeds the systemic pressure, the shunt switches to right-to-left.
This causes deoxygenated blood to bypass the lungs and enter the body => CYANOSIS
Eisenmenger’s Syndrome - O/E
RV heave
Clubbing
Cyanosis
Loud S2 (due to forceful shutting of the pulmonary valve)
A murmur depending on where the shunt is:
- Atrial septal defect: mid-systolic, crescendo-decrescendo murmur loudest at the upper left sternal border
- Ventricular septal defect: pan-systolic murmur loudest at the left lower sternal border
- Patent ductus arteriosus: continuous crescendo-decrescendo “machinery” murmur
Eisenmenger’s Syndrome - Mx
Ideally the underlying defect should be managed optimally or corrected surgically
Once significant pulmonary HTN has developed, the structural defects are considered irreversible and the only Tx is heart and lung transplant.
What should be considered with a fever and a new murmur?
INFECTIVE ENDOCARDITIS until proved otherwise
What is IE?
Who does it affect?
= an infection of the endocardial surface of the heart.
Patients with a structural abnormality of the heart (e.g. valve disease, valve replacements, congenital cardiac defects)
=> insidious onset, caused by normal GI/skin commensals
Patients with structurally normal heart valves (often IVDU)
=> Acute, fulminating presentation; Pathogenic organisms that directly invade the valve
Common bacteria involved in IE
Staphylococcus viridans = most common
Staph aureus / Strep epidermis both also seen
IE - RFs
- Previous IE
- Acquired valvular heart disease
- Valve replacement
- Structural congenital heart disease (excl. ASD or fully-repaired VSD/PDA)
IE - symptoms
Classical presentation = acute febrile illness plus a new murmur.
However, may present as insidious illness (malaise, lethargy, anorexia, arthralgia) and thus high index of suspicion is required.
Other Presentations may be distal infarctions or AKI due to immune complex deposition.
IE - O/E
Fever + changing / new heart murmur
Microscopic haematuria
Splenomegaly
Osler’s Nodes
Roth’s Spots
Janeway Lesions
Clubbing
Splinter haemorrhages
Petechial rash
Digital infarcts
IE - Ix
Bloods:
=> FBC, CRP/ESR, U&E
=> Cultures – 3 sets at different sites
Urinalysis:
=> Look for proteinuria and microscopic haematuria
ECG:
=> At regular intervals – can get MI due to emboli or conduction defects.
CXR:
=> To look for evidence of heart failure or abscess / emboli
Transthoracic Echocardiography:
=> Should be done in all patients with ?IE
=> Negative echo does not rule out endocarditis.
Duke’s Criteria
MAJOR
Positive culture (typical organism in 2 cultures)
Endocardial involvement on echo (vegetations, abscess, new regurgitation)
MINOR
Predisposition
Fever >38o
Vascular / immunological signs
Culture / echo positivity not sufficient for “major” criteria
–
Diagnosis can be made if there are 2 major or 1 major and 3 minor criteria.
Acute Infective Endocarditis
Bacterial proliferation in the valve leads to necrosis of the valve tissue, with rapid perforation of the valves.
Leads to acute cardiac failure.
Subacute Infective Endocarditis
As the infective organisms are poorly virulent, there is very gradual onset and destruction of the valves
Stimulation of thrombus formation leads to systemic embolization, and the persistent low grade inflammation leads to immunological phenomena
IE - complications
Systemic Emboli (or pulmonary abscess in right-sided disease)
Valvular incompetence and CCF
Glomerulonephritis
IE - management
If suspected, consult a microbiologist early.
EMPIRICAL Tx:
- Amoxicillin and gentamicin IV for 4 weeks
- Different regimen if prosthetic valve endocarditis or penicillin allergic.
Subsequent therapy is dependent on the organisms and sensitivities
IE - prevention
ABX prophylaxis is no longer recommended for people undergoing dental procedures (no evidence of any benefit)
Patients at risk of infective endocarditis should be:
=> Advised to maintain good oral hygiene;
=> Told how to recognise signs of infective endocarditis, and advised when to seek expert advice.
Blunt cardiac trauma
=> cardiac contusion
can give ECG changes similar to MI
Management is conservative.
Cardiac Tamponade - signs
Cardiac Tamponade is suggested by Beck’s triad:
- Hypotension
- Raised JVP
- Muffled heart sounds
Penetrating cardiac trauma
Complex investigation and management (often surgical) will be required.
CXR is vital due to risk of damage within the thoracic cavity, and should be upright if possible
Can cause cardiac tamponade
Cardiac Tamponade - Ix and Mx
Ix:
- CXR may show cardiomegaly with or without an epicardial fat pad sign suggesting a pericardial effusion.
- Echo = 1st line for diagnosis (diagnosis and approach planning for pericardiocentesis)
- CT provides valuable information about the possible nature of pericardial effusions based on the attenuation measurements
Tx:
- Time is bought with pericardiocentesis, prior to sternotomy and repair.
Myxoma
Signs, diagnosis & management
= Most common myocardial tumour
Benign, usually sporadic
Signs:
- Mimic either IE or mitral stenosis
Ix:
- Confirmed on echocardiogram
Tx:
- Excision
Constrictive Pericarditis
Pericardial Inflammation can result in constriction of the whole pericardium.
Causes - TB, RA, Pericardial trauma / radiotherapy
Clinical signs:
- Pulmonary and systemic congestion (as it affects all 4 heart chambers)
Tx:
- Excision of whole pericardium
Lifestyle limitations post-ACS
Work:
- May return to office work after two months
- Certain occupations (e.g. pilots, divers) should not return to work
- Heavy manual labourers should seek lighter work
Travel:
- Avoid air travel for 2 months
Sex:
- Avoid intercourse for 1 month
Driving:
- The DVLA do not need to be notified
- If successfully treated with PCI, driving can continue after 1 week
- Otherwise driving may recommence after 4 weeks
Driving Limitations with angina
The DVLA do not need to be notified.
Driving can continue unless angina occurs at rest / whilst driving / with emotion.
Recommence when adequate symptom control gained.
Driving Limitations with AAA
Notify the DVLA if >6cm
Annual review to permit licensing, will be disqualified if >6.5cm
Cardiac conditions and HGV Drivers
In general, all CV diagnoses lead to revocation of licenses for 6 weeks
=> 3 months post-CABG
Re-licensing can then be permitted if exercise / other functional requirements are met
Pathophysiology of pulmonary oedema
Occurs due to an increase in fluid in the alveolar wall (pulmonary interstitium), which then affects the interstitial spaces.
Pulmonary Oedema - Clinical Features
Dyspnoea
Paroxysmal nocturnal dyspnoea
Orthopnoea:
- Due to increased venous return on lying down
- Can be measured objectively by number of pillows required to sleep
Cough:
=> Producing frothy, blood-stained sputum
Presentation of acute pulmonary oedema
Severe dyspnoea
Productive cough
Anxiety and sweating
Cheyne-stokes respiration in LVF:
=> Cycling apnoea / hyperventilation due to impaired response of respiratory centre to CO2
Pulmonary Oedema - O/E
Tachypnoea
Tachycardia, with gallop rhythm
Raised JVP
Peripheral shutdown
Auscultation:
- Widespread course crackles / reduced breath sounds
- Wheeze can also be associated with pulmonary oedema and is referred to as ‘cardiac asthma’.
Pulmonary Oedema - Ix
ABG:
- Initially T1RF due to hyperventilation
- Later T2RF due to impaired gas exchange.
Bloods:
- FBC, U&E, glucose, D-dimer, CRP
CXR:
- Diffuse haziness (“bat wings”)
- Kerley B lines
- Upper zone vessel enlargement
- Cardiomegaly (HF)
- Pleural effusions
ECG:
- Tachycardia
- Arrythmia
- Signs of cardiac cause
Echo:
- To demonstrate a cardiac cause
Causes of pulmonary oedema
MOST COMMON = LVF
Increased capillary pressure:
- Cardiogenic – LVF, valve disease, arrythmias, VSD, cardiomyopathies, negatively inotropic drugs.
- Pulmonary venous obstruction
- Iatrogenic fluid overload
Increased capillary permeability:
- ARDS
- Infection – pneumonia/ sepsis
- DIC
- Inhaled toxins
Reduced plasma oncotic failure:
- Renal / Liver failure – hypoalbuminaemia
Lymphatic Obstruction:
- Tumour / parasitic infection
Others:
- Neurogenic – raised ICP / head injury
- PE
- Altitude
Pulmonary HTN in pulmonary oedema
Pulmonary HTN secondary to prolonged pulmonary oedema leads to irreversible structural changes to pulmonary arteries.
This in turn puts more pressure on the right ventricle of the heart, which eventually leads to RV hypertrophy and RHF => “cor pulmonale”
Acute Respiratory Distress Syndrome
= a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs
Due to the pulmonary response to either direct (inhalation) or indirect (blood-borne) insults, leading to non-cardiogenic pulmonary oedema
Causes of ARDS
DIRECT
Aspiration of gastric contents
Smoke / toxin inhalation
Pneumonia
Near-drowning
INDIRECT
Sepsis
Multiple trauma
Pancreatitis
Transfusion reactions
Anaphylaxis
Drug reactions
Pathophysiology of ARDS
Neutrophil infiltration of pulmonary capillaries leading to increased capillary permeability and protein-rich pulmonary oedema.
There is also damage to type 2 pneumocytes, leading to surfactant depletion and alveolar collapse due to lack of lung compliance.
ARDS - clinical features
SOB, tachypnoea, cyanosis
Hypoxaemia
Absence of signs of raised right atrial pressure
Diffuse bilateral infiltrates on CXR
Impaired lung compliance.
ARDS - Mx
These patients will often be admitted to ICU for respiratory / circulatory support.
Sit the patient up with 100% oxygen
Non-invasive positive pressure ventilation (e.g. CPAP) used initially
=> BUT most will require mechanical ventilation
IV nitrates titrated upwards until clinical improvement seen (or drop in SBP)
IV furosemide (40-80mg)
IV morphine + anti-emetic
Aminophylline if bronchospasm also present
The patient will then be kept on bed rest with continuous monitoring, and investigation / Tx for underlying cause.
Haemophilia A
- what is the deficiency?
- what is the mode of inheritance?
Factor VIII deficiency
X-linked recessive inheritance (but a high rate of new mutations)
Haemophilia B
Factor IX deficiency
(Also known as Christmas disease)
X-linked recessive inheritance
Haemophilia A/B - presentation
Major bleeds following minor trauma
Recurrent haemarthroses leading to crippling arthropathies
Compartment syndrome / nerve palsies can develop due to pressure effects.
Women can be CARRIERS and have a milder version of the disease.
Haemophilia A and B - Ix
- FBC
- Clotting screen – raised APTT
- Fibrinogen activity
Upon contacting haematology:
=> vWF
=> Intrinsic factor assays:
- Low factor VIII or IX (depending on type)
Haemophilia A and B - Mx
Avoid NSAIDs and IM injections
Minor bleeding:
- Compression & elevation
- Desmopressin (recombinant ADH) – raises factor VIII levels and may be sufficient
Major bleeding (e.g. haemarthrosis):
- Recombinant factor VIII / IX to raised factor levels to 50% of normal
Life-threatening bleeds:
- Raise levels to 100% of normal
Von Willebrand’s Disease
= the absence or abnormal function of vWF:
TYPE 1 – most common and least severe; due to reduced levels of vWF;
=> bleeding is mostly only a problem if after surgery/ injury/ dental surgery
TYPE 2 – vWF does not work properly
TYPE 3 – most severe and rarest; very low or no vWF;
=> Bleeding from the mouth, nose and gut is common
=> Also joint and muscle bleeds after an injury.
von Willebrand’s Disease - Presentation
This gives symptoms of platelet type disorder:
=> Mucocutaneous bleeding - Epistaxis / menorrhagia / petechial rash
Haemarthroses are rare
Mode of inheritance of von Willebrand’s disease
autosomal recessive or autosomal dominant
=> Recessive – type 3 / complete absence of detectable vWF (20%)
=> Dominant – type 1 or 2; less severe depletion of vWF (80%)
Von Willebrand’s disease - Mx
Expert Mx is required:
- Transexamic acid for mild bleeding
- Desmopressin / recombinant factor VIII for more severe bleeds (vWF has a secondary role of binding factor VIII to prevent destruction, so low factor VIII levels co-exist).
What are causes of clotting factor deficiency
- Haemophilia
- Liver disease
- DIC
- Vitamin K deficiency
- Anticoagulant drugs
Bleeding Disorder Assessment - Hx
Site of bleed:
=> Muscle / joint bleeds – coagulation issue
=> Purpura / epistaxis / menorrhagia / GI haemorrhage – platelet issue
=> Recurrent bleeds at one site – local endothelial abnormality
Duration of Hx / FHx
=> Congenital vs. acquired
Seriousness?
=> Spontaneous bleeds indicate a more serious issue than post-traumatic bleeds
Surgical Hx
=> Bleeding that starts immediately after => suggests platelet issue
=> Bleeding that starts several hours later => suggests coagulation issue
PMHx:
=> Renal / liver failure ?
DHx:
=> Anticoagulants
=> Steroids / NSAIDs
Bleeding Disorder Assessment - O/E
Skin:
=> Any bruises / purpura / telangiectasia?
Joints:
=> Any evidence of haemarthrosis?
Abdomen:
=> Splenomegaly?
=> Evidence of hepatic dysfunction?
Secondary Haemostasis
= the process of stabilisation of the soft haemostatic plug through a complex interaction between platelet membrane, enzymes and coagulation factors
Clotting Factor I and Ia
I = Fibrinogen
Ia = Fibrin
Clotting Factor II and IIa
II = prothrombin
IIa = thrombin
Coagulation cascade
Clotting factors are primarily synthesised in the liver, and many act as serine proteases to activate other factors.
INTRINSIC or EXTRINSIC pathway can be activated, but both activate a final common pathway that leads to production of fibrin and thus a thrombus can be formed.
At the same time, thrombin, in the presence of calcium ions, activates factor VIII which stabilises the fibrin clot by cross-linking fibrin molecules.
Sources of vitamin K
Found in leafy green vegetables, dairy products and soya beans.
Intestinal flora can also synthesise many forms of vitamin
Vitamin K - actions
What can cause deficiency and what can this lead to?
VitK is a co-factor necessary for the production of some clotting factors.
=> Factor II, VII, IX and X
Deficiency of VitK thus leads to clotting factor deficiencies, leading to an increased PT and haemorrhage.
Deficiencies arise from:
- Malabsorptive conditions (VitK = fat soluble vitamin)
- Cholestatic jaundice (no bile salts)
- ABX (gut flora disturbances).
Physiological Inhibitors of Coagulation
Anti-thrombin III – serine protease inhibitor (potentiated by heparin)
Activated protein C – also generated by vitamin K, and activated by thrombin.
=> APC acts with the co-factor protein S to induce fibrinolysis
=> It destroys factor V and VIII, reducing further thrombin generation and inhibits stabilisation of the fibrin clot.
Fibrinolysis
Plasminogen is converted to plasmin by tissue plasminogen activator (t-PA), produced by the endothelium.
Many mediators, including thrombin and APC, stimulate the release of t-PA.
Plasmin is a serine protease that breaks down fibrinogen and fibrin into fibrin degradation products (FDPs) – e.g. D-dimer
=> D-dimer presence in the plasma thus indicates that the coagulation mechanism has been activated.
Lab tests for primary haemostasis
FBC and Blood Film – platelet number and morphology
Platelet function tests – e.g. PFA/closure time, platelet aggregometry.
Complex platelet test by specialist
Von Willebrand factor assays
Lab tests for secondary haemostasis
CLOTTING SCREEN
=> PT (extrinsic)
=> APTT (intrinsic).
=> INR
=> APTT ratio
=> derived fibrinogen
Prothrombin Time (PT)
Tests the extrinsic pathway, by addition of a tissue factor substitute to the patient’s plasma.
Prolonged in:
- Liver disease
- Patients on warfarin
Activated partial Thromboplastin Time (APTT)
Addition of a surface activator to the plasma
Tests the intrinsic (contact) pathway
Used for monitoring of unfractionated heparin (not required for LMWH)
INR
Ratio of patient’s PT to a normal control whilst using an international reference preparation (standardises laboratories worldwide)
0.9 – 1.1 = normal range
Used for warfarin dosing
Thrombin Time:
Addition of thrombin to the patient’s plasma
Prolonged with:
- Fibrinogen deficiency / abnormal function
- Inhibitors such as heparin
Primary Haemostasis
= Characterised by vascular contraction, platelet adhesion and formation of a soft haemostatic plug.
How does the endothelium prevent platelet aggregation in homeostatic conditions?
when the endothelium is in continuity it secretes mediators such as prostacyclin (PGI2) and nitric oxide that prevent platelet adhesion.
How does endothelial damage initiate primary haemostasis?
Vasoconstriction => slows blood flow, enhances platelet adhesion and activation.
Exposed collagen and vWF => triggers platelet adhesion
Platelet adhesion leads to degranulation of the platelets, releasing ADP
ADP stimulates further platelet aggregation at the site
Platelets also synthesise the prostaglandin thromboxane A2 (TXA2), which causes both vasoconstriction and further aggregation.
Receptors on the platelet surface then activate the coagulation cascade, which generates fibrin to form a fibrin/platelet thrombus (= soft haemostatic plug).
This process is short-lived and the weak plug is easily sheared off.
Aspirin antiplatelet MOA
Low-dose (75mg) aspirin irreversibly inhibits COX enzyme, preventing conversion of arachidonic acid to endoperoxides such as PGI2 and TXA2.
After administration of aspirin, the nuclei of endothelial cells are quickly able to secrete mRNA for PGI2 production.
The anucleate platelets cannot form TXA2, so levels decrease until new platelets are formed (in approximately 7 days).
Low-doses of aspirin every 24-48 hours thus decrease synthesis of TXA2, without massively affecting PGI2 production.
MOA of clopidogrel
can be used as an alternative or an adjunct to aspirin
It works as an ADP receptor antagonist, thus preventing glycoprotein expression and platelet aggregation.
Thrombocytopaenia - Causes
REDUCED PRODUCTION
Aplastic Anaemia
Marrow Infiltration
Marrow Suppression
EXCESS DESTRUCTION
Immune thrombocytopaenic purpura (ITP)
Other autoimmune causes – SLE, CLL, viruses
Thrombotic thrombocytopaenic purpura (TTP)
Haemolytic uraemic syndrome (HUS)
Sequestration – hypersplenism
Thrombocytopaenia - presentation
Bruising / purpura of the skin
Epistaxis / menorrhagia
Major haemorrhage is very rare
Physical examination is generally normal.
Immune Thrombocytopaenic Purpura
= isolated thrombocytopaenia without an isolated cause.
Presentation:
- In children, ITP is usually acute and self-limiting – following a virus or immunisation.
- In adults, the presentation is usually less acute, classically in women with other autoimmune disorders.
Immune Thrombocytopaenic Purpura - Ix
FBC – only thrombocytopaenia seen
Clotting screen – to r/o other clotting disorders
Bone marrow examination:
- Not usually performed in children
- Normal / increased megakaryocyte numbers found, otherwise normal
Platelet autoantibodies
=> Positive in 70% of patients, but does not confirm diagnosis.
Immune Thrombocytopaenic Purpura - Mx
Children are not usually treated.
=> If clinically necessary, they may be treated with prednisolone or IVIG
Chronic thrombocytopaenia is rate, and requires specialist management.
In adults:
=> corticosteroid are 1st line
=> IVIG can be used if a rapid rise in platelets is required
=> Splenectomy may be 2nd line
Platelet transfusions are reserved for severe haemorrhage.
What hormones does the anterior pituitary synthesise and secrete?
Growth Hormone (GH)
Prolactin
Adrenocorticotropic Hormone (ACTH)
Thyroid-stimulating Hormone (TSH)
Gonadotrophin Luteinizing Hormone (LH)
Follicle Stimulating Hormone (FSH)
What hormones does the posterior pituitary store and secrete?
stores and secretes hormones that were produced in the hypothalamus (connected by the pituitary stalk)
Anti-diuretic Hormone (ADH)
Oxytocin
Pituitary Adenoma
Benign tumour of the glandular tissue (BUT can be life-threatening due to mass effects or secretory actions)
Size:
- >1cm = macroadenoma
- <1cm = microadenoma
Tumours are classified as “functioning” or “non-functioning” (silent) on the basis of whether they are secretory or not.
Non-functioning Pituitary Adenoma -Presentation
Bitemporal Hemianopia – due to compression of the optic chiasm
Ocular Palsies – due to compression of CN III, IV or VI
Hypopituitarism – destroys the normal functioning tissue
Signs of raised ICP
Hypothalamic compression symptoms – altered appetite, thirst, sleep/wake cycle
Functioning Pituitary Adenoma - Presentation
Acromegaly – excessive GH production
Hyperprolactinaemia – excessive prolactin production
Cushing’s Syndrome – excessive ACTH production
Functioning Adenomas can also cause any of the mass effects.
Many tumours can secrete multiple hormones, however tumours producing TSH / LH / FSH are very rare.
Hyperprolactinaemia
Prolactin stimulates milk production in the breast, and also inhibits GnRH and gonadotropin production.
Clinical Features:
- Gynaecomastia
- Galactorrhoea in females (spontaneous and expressible)
- Oligo/amenorrhoea
- Decreased libido
- Subfertility
- Arrested puberty in younger patients
In the long-term, osteoporosis may develop due to androgen/oestrogen deficiency.
Causes of hyperprolactinaemia
- Pituitary Adenoma
- Breast stimulation / stress
- Drug induced
- Idiopathic
Pituitary Adenoma - Ix
pituitary MRI
Pituitary Adenoma - Mx
Dopamine Agonists are 1st line (dopamine inhibits prolactin release)
=> Lifelong Ropinirole / bromocriptine
=> These reduce tumour bulk without the surgical risks
=> Sx usually recur on stopping medication
Surgery is 2nd line if medical Tx ineffective
Excess growth hormone
GH stimulates skeletal and soft tissue growth
Excess GH can cause:
=> Gigantism in children (if prior to epiphyseal plate closure)
=> Acromegaly in adults
Causes of acromegaly
Acromegaly is almost exclusively due to pituitary tumours
Rarer causes – paraneoplastic release of GH from non-pituitary tumours.
Acromegaly - Ix
Raised IGF-1 level
- Used as this level correlates with GH levels over the past 24 hours (GH levels themselves are too variable)
- Mainly used for monitoring rather than diagnosis
Glucose tolerance test:
- Normally will suppress GH secretion
- In acromegaly, concentrations are >2mcg/mL at 2 hours.
Acromegaly - Symptoms
Change in appearance
Increased hand/foot size
Tiredness
Excessive sweating
Poor libido
Symptoms of diabetes
Headaches
Visual Deterioration
Symptoms of hypopituitarism
Acromegaly - Signs
Protruding mandible
Prominent supraorbital ridge
Interdental separation
Large tongues
Spade-like hands/feet
Tight rings
Visual field defects
HTN
Acromegaly - Mx
Somatostatin analogues may be used to shrink the tumour
=> Short-term prior to surgery
=> Long-term if surgical removal not possible.
Surgical Mx = via transphenoidal approach
Cushing’s Syndrome - causes
- Exogenous administration of steroids (most common)
- Cushing’s disease = Increased ACTH from the pituitary
- Ectopic ACTH (non-pituitary ACTH-secreting tumour – classically small cell lung cancer)
- Excess adrenal cortisol production
How does Cushing’s Syndrome differ from Cushing’s disease?
Cushing’s syndrome = umbrella term describing the symptoms of increased circulating glucocorticoid.
Cushing’s disease = specifically due to increased ACTH from the pituitary
Cushing’s Syndrome - Presentation
SYMPTOMS
Central weight gain
Change of appearance
Depression
Insomnia
Poor libido
Thin skin/easy bruising
Excess hair growth / acne
Diabetes symptoms
SIGNS
Moon face
Frontal balding
Striae
HTN
Pathological Fractures
“Buffalo hump”
Proximal myopathy
(There may also be hypokalaemia due to the mineralocorticoid activity of cortisol)
Cushing’s Syndrome - Ix
- Overnight dexamethasone suppression test
=> Normal = negative feedback leads to cortisol level <50 mmol/L
=> Cushing’s = failure to suppress cortisol secretion - If abnormal, localisation tests are required:
=> Plasma ACTH – if undetected, adrenal cause is likely => adrenal CT
=> If ACTH is detectable, pituitary vs. ectopic sources must be separated. - High-dose dexamethasone suppression test:
- Complete / partial suppression indicates Cushing’s disease (the pituitary retains some feedback control) => MRI pituitary
- No suppression indicates an ectopic source => CXR/find primary tumour
What is Panhypopituitarism?
How can it present?
How is it diagnosed?
= Defective production of all pituitary hormones
PRESENTATION
- Fatigue, myalgia, hypotension – GH/ ACTH deficiency
- Diabetes insipidus – ADH deficiency
- Hypothyroidism – TSH deficiency
Can have pituitary or hypothalamic causes
DIAGNOSIS
- Pituitary hormones = low
- Effector gland hormones = low
- Low response to stimulation tests
- Imaging to localise pathology
Panhypopituitarism - causes
Pituitary causes:
- Obliteration of the pituitary by primary/metastatic tumour
- Surgical removal / irradiation of pituitary
- Ischaemic necrosis due to hypotensive shock
Hypothalamic causes:
- Destruction of hypothalamus by primary tumour/ infection/ sarcoid/ infection.
Posterior pituitary disease
Occur mainly as a result of damage to the hypothalamus (e.g. tumour invasion or infarction).
Failure of ADH production leads to Cranial diabetes insipidus (as opposed to nephrogenic DI)
Excessive ADH production leads to SIADH
Diabetes Insipidus
Failure of ADH production leads to cranial diabetes insipidus
=> Presents with polyuria and polydipsia, hypernatraemia
Ix:
- Low urine osmolality
- High serum osmolality
- Water deprivation test
Mx = treat underlying cause; desmopressin (synthetic ADH) can be used in cranial DI.
Causes of SIADH
Post-operative from major surgery
Infection, particularly atypical pneumonia and lung abscesses
Head injury
Medications (thiazide diuretics, carbamazepine, vincristine, cyclophosphamide, antipsychotics, SSRIs, NSAIDSs,)
Malignancy, particularly small cell lung cancer
Meningitis
Excess pituitary secretion
What is SIADH?
Excessive ADH production results in excessive water reabsorption in the collecting ducts.
This water dilutes the sodium in the blood so you end up hyponatraemia
The excessive water reabsorption is not usually significant enough to cause a fluid overload, therefore you end up with a “euvolaemic hyponatraemia”.
The urine becomes more concentrated as less water is excreted by the kidneys therefore patients with SIADH have a “high urine osmolality” and “high urine sodium”.
SIADH - Ix
- Assess Fluid status – euvolaemia
- U&Es – hyponatraemia
- Urine sodium and osmolality will be high
SIADH - Mx
Treat cause;
Fluid restriction (0.5 – 1 L);
Correct sodium SLOWLY (~10 mmol/day)
Potentially ADH receptor blockers or Demeclocycline (a tetracycline antibiotic that inhibits ADH)
Goitre
= painless enlargement of thyroid gland. It can be defined by certain characteristics:
- Diffuse vs. nodular – pattern of swelling
- Simple vs. toxic – actively secreting thyroid hormone
- Benign vs. malignant
Diffuse Goitre - causes
Physiological
- Puberty
- Pregnancy
Autoimmune
- Grave’s disease
- Hashimoto’s disease
Thyroiditis
- Subacute (De-Quervain’s) thyroiditis
- Riedel’s thyroiditis
Endemic
- Iodine deficiency
Drugs
- Anti-thyroid drugs
- Lithium
- Iodine excess
- Amiodarone
Nodular Goitre - causes
Multinodular
- Toxic multinodular goitre
- Subacute thyroiditis
Solitary Nodule:
- Follicular adenoma
- Benign nodule
- Thyroid malignancy
- Lymphoma
- Metastasis
- OR one prominent nodule from a multinodular goitre
Infiltration (rare):
- TB
- Sarcoid
Goitre - Ix
FBC – assess for related anaemia
ESR – may indicate thyroiditis / autoimmune disease
TFTs
Thyroid autoantibodies
CT neck and thorax – if pressure Sx
USS – to distinguish between solid and cystic masses (not required in all cases)
Fine needle aspiration for cytology (FNAC) – if concern regarding malignancy.
Goitre - Mx
Mx depends on whether the patient is hyperthyroid or hypothyroid.
In a euthyroid patient, Tx is not required for a non-malignant nodule unless it is causing pressure Sx.
Hyperthyroidism / thyrotoxicosis - causes
COMMON
Grave’s Disease
Toxic multinodular Goitre
LESS COMMON
Solitary Toxic Adenoma
Thyroiditis
Drug-induced - Amiodarone; Excess levothyroxine
Exercise Iodine intake
Hashitoxicosis (the hyperthyroid phase of Hashimoto’s disease)
RARE
Secondary causes:
- TSH secreting pituitary adenoma
- Resistance to thyroid hormone
Grave’s Disease - pathophyisiology
IgG autoantibodies stimulate thyroid follicular cells, out of the normal pituitary feedback mechanism => HYPERTHYROIDISM
Toxic multinodular Goitre / Solitary Toxic Adenoma
Both causes of hyperthyroidism
hyperactive nodule(s) develop, outside of TSH control
Hyperthyroidism - symptoms
Anxiety / irritability
Heat intolerance
Increased appetite
Palpitations
Weight loss
Tremor
Diarrhoea
Fatigue / weakness
Can rarely present with thyroid crisis/thyroid “storm”
Hyperthyroidism - Signs
which signs are specific to Grave’s disease?
Lid retraction / lid lag
Goitre
Systolic HTN
Tachycardia / AF
Tremor
Hyperreflexia
Warm peripheries
Proximal Weakness
Pre-tibial myxoedema
Grave’s Ophthalmopathy*
Acropachy*
Grave’s Ophthalmopathy
Lagophthalmos – inability to close eyes completely
Exophthalmos / proptosis – bulging eyes
Ophthalmoplegia – especially affecting upwards and lateral gaze
Periorbital oedema
!! Graves’ Ophthalmopathy is much more common in smokers.
Thyroid crisis / “storm” - presentation and management
Generally occurs in periods of stress (infection, surgery, childbirth) in people with untreated/uncontrolled hyperthyroidism.
- Hyperpyrexia
- Severe tachycardia
- Profuse sweating
- Confusion / psychosis
- If untreated, coma and death
Treat with:
- Propylthiouracil, propranolol, sodium iodide, high dose steroids
- Supportive measures
Hyperthyroidism - Ix
TSH – fully suppressed (unless in rare cases of pituitary adenoma)
Free T3/4 – elevated
=> Typically both elevated, in rare cases there can be T3-toxicosis with T4 within reference range.
TSH receptor antibody (TRAb) – sensitive and specific for Grave’s disease
Thyroid Peroxidase (TPO) is not elevated in all Grave’s patients, so no longer routinely used.
Technetium uptake scan – if TRAb not present
=> Diffuse pattern of uptake in Grave’s disease
=> One or more “hot” nodules in toxic multinodular goitre
=> Reduced/absent uptake in thyroiditis
Radioiodine scans can be used, but are less common
CT/MRI Orbit – to assess extent of eye disease in Grave’s
Management of hyperthyroidism in primary care
Non-selective beta-blocker – e.g. propranolol
=> 20-40 mg t.d.s for rapid relief of symptoms
=> May be the only Tx required for cases of thyroiditis
Refer to specialist endocrinologist
=> Options include antithyroid drugs, radioactive iodine therapy, surgical management.
Management of hyperthyroidism in secondary care (endocrinologist)
Patients with Grave’s disease are usually offered an intermediate course of antithyroid therapy (titration vs. block and replace)
In other pathologies, antithyroid drugs control but do not cure the disease:
=> Patients are offered a choice of radio-active iodine (RAI) therapy or surgical management.
- RAI generally first line
- Drugs will always be used prior to RAI / surgery to render the patient euthyroid before definitive Tx.
- Antithyroid drugs may be used long-term if these therapies are unsuitable.
Different regimens of antithyroid drug therapy
Titration regimens – start at a high dose and titrate down until the patient is euthyroid.
“Block and replace” – maintain a high dose, and thyroxine added in.
What are the two Antithyroid drug options?
How do they work?
What are possible side effects?
Carbimazole is 1st line
Propylthiouracil is 2nd line
=> Due to risk of severe liver injury
Both act as preferred substrate for thyroid peroxidase, the key enzyme in thyroid hormone synthesis.
SEs:
- Both can cause skin rashes or the more serious agranulocytosis/thrombocytopaenia.
- Carbimazole can also cause cholestatic jaundice.
Radioactive Iodine Therapy
131I is used as first line in non-Grave’s pathology; or following failure of drug therapy in Grave’s.
It is taken up by the thyroid cells, and induces DNA damage and cell death.
Antithyroid drugs must be discontinued prior to therapy for at least 1 week to allow adequate uptake.
What are the contraindications for RAI in hyperthyroidism
What are the implications for fertility/pregnancy?
- Pregnancy
- Active Grave’s ophthalmology (can cause worsening of eye symptoms)
Patients should avoid prolonged contact with children for 3 weeks after treatment, and should not attempt to conceive for 6 months
When is surgery indicated for hyperthyroidism
Surgery is indicated if:
- other measures have failed or are contraindicated,
- There is suspicion of malignancy
- To manage a large toxic goitre
Causes of hypothyroidism
COMMON
Hashimoto’s Thyroiditis (goitre)
Atrophic Thyroiditis (no goitre)
Previous Tx for hyperthyroidism
LESS COMMON
Drugs (Amiodarone, iodine excess, lithium)
Iodine Deficiency
Thyroiditis
Secondary causes (Hypothalamic/pituitary disorders)
RARE
Congenital agenesis
Neoplastic infiltration
Hashimoto’s Thyroiditis
= most common cause of hypothyroidism in the UK
T-cell destruction of the gland, plus B-cell secretion of inhibitory TSH-receptor antibodies.
Often an initial hyperthyroid phase.
There will be a goitre
Hypothyroidism - Symptoms
Fatigue
Depression / psychosis
Cold intolerance
Weight gain
Constipation
Menorrhagia
Myxoedema coma (rare)
Hypothyroidism - signs
Hair loss
Loss of outer third of eyebrow
Anaemia
Hoarse voice
Goitre
Bradycardia
Dry skin
Hyporeflexia
Hypothyroidism - Ix
FBC – anaemia
=> Macrocytic due to co-morbid pernicious anaemia
=> Microcytic due to menorrhagia
TFTs:
=> Raised TSH, reduced free T4 in primary causes
=> Low TSH in hypothalamic disease or “sick thyroid syndrome” (due to non-thyroidal illness)
TPO autoantibodies
=> Raised in Hashimoto’s
Cholesterol – can be raised in hepatic hypothyroidism
Hypothyroidism - Mx
Levothyroxine
=> Low starting dose, titrated up to clinical effect
=> Reassess every 4-6 weeks, until TSH is in the lower half of the reference range in primary disease.
=> TSH is unreliable in secondary disease, titrate based on free T4 levels and clinical symptoms
Acute Thyroiditis
Relatively uncommon
May follow an URTI
Presentation:
- Initially fever and malaise, plus thyroid swelling and tenderness
- Initially there are thyrotoxic features, as stored hormone is released.
- After this, the patient develops hypothyroidism, which is usually transient but can occasionally be permanent
There is classically low/absent uptake on technetium scanning
Tx:
- Propranolol in thyrotoxic phase
- Simple analgesia
- Occasionally prednisolone 30mg/day is used.
Calcium distribution in the body
99% of the body’s calcium is in the bone – combined with phosphate as hydroxyapatite.
40% of plasma calcium is bound to albumin, and thus is inactive (Only free Ca2+ is biologically active)
=> Acidotic states increase ionised calcium, by decreasing albumin binding.
=> Alkalotic states decrease ionised calcium, by increasing albumin binding
How can serum albumin have an effect on serum calcium levels?
40% of plasma calcium is bound to albumin
Many labs will adjust for a low/high serum albumin to give a measure of the ionised calcium present (“adjusted calcium”)
Normal Plasma Calcium
Plasma calcium normal range = 2.2 - 2.6 mmol/L
Maintaining calcium at optimum range ensures normal excitability of nerve and muscle.
Calcium is also required for clotting and complement cascades
When and from where is PTH secreted?
There are 4 pea-sized parathyroid glands, lying just posteriorly to the thyroid.
=> These glands have calcium and vitamin D receptors.
The chief cells of the parathyroid glands are responsible for secreting parathyroid hormone (PTH):
=> when plasma calcium levels are low.
=> in response to low vitamin D, or high phosphate levels.
What are the effects of PTH?
PTH works to increase plasma calcium by:
- Directly stimulating calcium reabsorption from bone, via increased osteoclast activity.
- Directly increasing renal tubular calcium reabsorption.
- Indirectly stimulating increased GI calcium absorption.
=> Via increased vitamin D activation in the kidney.
PTH also has a secondary effect of increasing renal phosphate excretion
Vitamin D sources
ENDOGENOUS - synthesised in the skin, forming D3 (cholecalciferol).
=> Action of UV light on the precursor to vitD (7-dehydrocholesterol)
EXOGENOUS - ingested as D3/D2
=> D3 – found in fish, liver, dairy products
=> D2 – found in plants/fungi (less potent than D3)
Calcitonin
Calcitonin is secreted by the parafollicular/ “C” cells of the thyroid gland
Secreted in response to increased plasma calcium levels.
It acts to decrease plasma calcium levels, by antagonism of the effects of PTH on the bone.
=> Reducing osteoclast activity
=> Decreasing renal resorption of calcium and phosphate.
HOWEVER the effects of calcitonin are controversial (evidence that there aren’t many effects).
Possible causes of hypercalcaemia
- Excessive PTH secretion
- Hyperparathyroidism
- Ectopic PTH secretion (rare) - Malignant disease
- Myeloma
- Bone metastases
- PTH-related protein secreting tumours (e.g. SCC of lung/other tissues) - Excess action of Vit D
- Excessive calcium intake - “Milk-alkali syndrome”
- Drugs
- Hereditary - Familial hypocalciuric hypercalcaemia
Features of hypercalcaemia
Mild hypercalcaemia (<3.0 mmol/L) is usually asymptomatic.
Symptoms in hypercalcaemia (>3.0 mmol/L):
- BONES – bone pain, muscle weakness, chondrocalcinosis
- STONES – renal colic (stones), polyuria, AKI/CKD
- ABDOMINAL GROANS – abdominal pain, vomiting, constipation, pancreatitis, GI ulcers
- PSYCH MOANS – depression, confusion, tiredness, hypotonicity.
ECG will slow reduced QT interval, and this can lead to cardiac arrest.
Primary Hyperparathyroidism
80% due to parathyroid adenomas
20% due to diffuse hyperplasia of the glands
PTH levels raised, calcium levels raised.
Tx = Parathyroidectomy
Parathyroidectomy in hyperparathyroidism
Tx for primary and tertiary hyperPTH
Indicated even in many asymptomatic cases, due to potential long-term adverse effects.
Serum calcium should return to normal within 24h post-surgery
There may be post-op hypocalcaemia (AdCal is usually given for 14 days post-op)
Secondary Hyperparathyroidism
PHYSIOLOGICAL hypertrophy of all parathyroid glands in response to hypocalcaemia
Seen in renal disease or VitD deficiency
PTH levels raised, calcium levels are low/normal
Tx = PTH will return to normal if the cause of hypocalcaemia can be corrected.
Tertiary hyperparathyroidism
Occurs after long-standing secondary hyperparathyroidism
Most commonly occurs in renal failure
Plasma calcium is raised, PTH levels raised
Phosphate is often grossly raised
Tx = Parathyroidectomy usually necessary.
How can you differentiate primary and tertiary hyperPTH?
Primary can be separated from tertiary hyperparathyroidism fairly easily based on clinical presentation, and phosphate levels are also helpful
=> Phosphate low/normal in primary, grossly raised in tertiary.
Hyperparathyroidism - Ix
- PTH – raised
- Ca2+ – raised (if primary/tertiary)
- PO43-
- ALP – raised
- 24h urinary calcium – raised
- DEXA scan – vital to assess extent of osteoporosis
- Tumour localisation:
=> Technetium scanning – show areas of increased uptake
=> USS (requires highly skilled operator)
MEN Syndromes
= multiple endocrine neoplasia
AUTOSOMAL DOMINANT INHERITANCE
MEN 1
- Pancreatic endocrine tumours – gastrinoma / insulinoma
- Pituitary adenoma
- Parathyroid adenoma (causing hyperPTH)
MEN2a:
- Thyroid – medullary carcinoma
- Adrenal – PCC
- Parathyroid – hyperplasia (causing hyperPTH)
MEN 2b:
- Thyroid – medullary carcinoma
- Adrenal – PCC
- Mucosal neuromas
- Marfanoid appearance.
Mx - Acute Hypercalcaemia
If Ca2+ = >3.5 mmol/L and severe symptoms:
- IV Fluids
=> 0.9% NaCl to increase calcium clearance.
=> Aim for 3-6L over the first 24 hours.
(Diuretics no longer routinely used, but may be considered if there is a risk of fluid overload.) - Bisphosphonates:
- Single dose of pamidronate
- Lowers calcium over 2-3 days. - Calcitonin:
- May be used to rapidly reduce levels in life-threatening hypercalcaemia (however effects are short-lived) - Dialysis:
=> May be required if there is renal impairment
Further Mx is related to investigating and treating the cause of hypercalcaemia.
Causes of HYPOcalcaemia
- ARTIFACT of low serum albumin if not “corrected”.
- With low PTH (hypoparathyroidism)
- Idiopathic / primary hypoparathyroidism
- H&N surgery / radiation
- Infiltration – sarcoid / malignancy
- Congenital absence of the gland (DiGeorge Syndrome)
- Severe hypomagnesaemia (impairs PTH secretion) - With High PTH:
- Vitamin D deficiency
- Acute pancreatitis
- Alkalosis
- Acute hypophosphatemia – renal failure, rhabdomyloysis, tumour lysis
- Drugs – bisphosphonates, calcitonin
What electrolyte disturbance goes hand-in-hand with hypocalcaemia?
What is the clinical relevance?
Severe hypomagnesaemia impairs PTH secretion
Always check serum magnesium levels
Replacing magnesium is essential (calcium will not increase otherwise)
Hypocalcaemia - presentation
Signs of Peripheral irritability:
- Tetany / cramps
- Carpo-pedal spasm
=> Happens especially after occlusion of brachial artery (Trousseau’s sign)
=> Tapping over facial nerve causes twitches – Chvostek’s sign - Seizures
- Depression / anxiety
- Perioral paraesthesia
- Cataracts
Hypocalcaemia - Ix
Serum calcium – low
Serum PTH – high / low
=> Check parathyroid antibodies if low
Serum vitamin D – r/o deficiency
ECG – prolonged QT interval
Hypocalcaemia - Mx
Mild/moderate symptoms:
=> AdCal (calcium and vitamin D)
Severe symptoms:
=> Calcium gluconate IV, 10ml of 10% bolus, then maintenance infusion.
=> Start AdCal without delay.
=> Find and treat the cause.
If hypomagnesaemia, replace magnesium as calcium will not increase otherwise.
Mycobacterium Tuberculosis
Small rod-shaped bacteria (bacilli)
Have a waxy coating that makes gram staining ineffective. They are resistant to the acids used in the staining procedure (“acid-fastness”).
=> “ACID FAST BACILLI”
They then stain red with Zeihl-Neelsen staining
Infection affects predominantly the lungs, lymph nodes and gut.
TB - RFs
- Non-UK born patients (areas where TB is endemic – e.g. South Asia, Africa)
- Immunocompromise
- Those with close contacts with TB.
- People living in overcrowded conditions
- Alcohol /drug abuse
Multi-Drug Resistant TB
strains that are resistant to more than one TB drug making them very difficult to treat.
The most common drug resistance in the UK is isolated isoniazid, with resistance to Rifampicin being the marker for MDR-TB
Primary TB - pathophysiology
= the syndrome produced by M. tuberculosis infection in those not previously affected
There is a mild inflammatory response at the site of the infection:
- Common sites of initial infection are sub-pleural in the mid zones of the lungs, in the pharynx or terminal ileum
- Infection will then spread to hilar, cervical or mesenteric nodes respectively.
1-2 weeks after infection, with the onset of immune sensitivity, the tissue reaction at both sites of the primary complex changes to form characteristic caseating granulomas
Viable bacteria may remain within the primary complex, giving latent TB.
TB - primary complex
= The combination of infective focus and lymph node involvement is known as the primary complex.
TB - Ghon focus
the infective focus of TB in the lung
Primary TB - presentation
Usually asymptomatic or have a single enlarged lymph node that may be palpable if cervical.
There are several methods by which primary TB can become symptomatic:
- The Ghon focus can erode through the visceral pleura to discharge organisms and cause TB pleurisy / pleural effusions
- Enlarged hilar lymph nodes can cause bronchial obstruction and collapse
- The hilar lymph nodes can also erode into the bronchus and rupture, causing TB bronchopneumonia
- The enlarging nodes can erode into vessels, giving miliary dissemination to the lung or systemic dissemination.
- Erythema nodosum is common in primary disease.
Symptomatic presentation is more common in patients with incomplete immunity.
Secondary TB - pathophysiology
M. tuberculosis re-infection in tuberculin-sensitive individuals.
=> Infection can be from exogenous sources or more commonly from “reactivation” from a healed primary complex
There is immediate granulomatous response to the disease, thus regional lymph involvement is not common
The lesion may heal with fibrosis and calcification if the immune system is strong.
=> Will progressively enlarge in those with poor immune systems.
=> This has greater risks of eroding into vessels / airways
TB - Assman focus
Secondary infection in the lung => classical apical lesion termed an Assman focus, with destruction of the lung parenchyma leading to cavitation.
Secondary TB - presentation
Earliest symptoms are non-specific – malaise, night sweats, anorexia, weight loss.
Specific symptoms can occur late:
- Productive cough
- +/- small amounts of haemoptysis
- Pleural pain
Can present with pneumonia or pleural effusion
O/E:
- May only be a fever and apical crepitations
- May be clubbing in advanced disease
Ix for Suspected active pulmonary TB
SPUTUM SAMPLES – at least 3, including one morning sample.
=> Microscopy for acid-fast bacilli, results within 24h
=> PCR – if rapid diagnostic results are required or suspected MDR-TB (however this will not differentiate between active and latent TB)
=> Culture = gold-standard diagnostic test; but takes 6 weeks.
If sputum samples are negative, bronchoscopy with biopsy or bronchoalveolar lavage may be useful.
CXR
Investigate for extra-pulmonary disease as clinically indicated.
How might TB appear on CXR?
Primary TB may show patchy consolidation, pleural effusions and hilar lymphadenopathy
Reactivated TB may show patchy or nodular consolidation with cavitation (gas filled spaces in the lungs) typically in the upper zones
Disseminated Miliary TB gives a picture of “millet seeds” uniformly distributed throughout the lung fields
Ix for Latent TB
- Mantoux test
- Interferon-gamma Release Assay
=> also required to diagnose latent TB in immunocompromised individuals, as they can have false negatives in skin tests
Positive results should lead to assessment for active TB (these tests cannot differentiate between active/latent TB)
=> If no evidence then treat for latent TB
Mantoux test
TB antigen (does not contain live bacteria), injected intradermally on the arm; size of wheal reaction monitored:
=> A positive result indicates either previous vaccination, latent or active TB.
Reactions >5mm
Considered positive in immunosuppressed individuals, those with prior TB or recent contacts
Reactions >10mm
Considered positive in those with RFs
Reactions >15mm
Considered positive in any individual
Active TB - Mx
Consider admission if severely unwell
Assess risk factors for MDR TB (and assess with PCR if suspected)
Normal ABX Regimen:
R Rifampicin => 6 months
I Isoniazid(+ prophylactic pyridoxine) => 6 months
P Pyrazinamide => 2 months
E Ethambutol => 2 months
(If CNS involvement, the isoniazid and rifampicin are continued for 12 months)
NOTIFIABLE DISEASE
What are risk factors for MDR TB?
- Previous TB treatment
- From endemic areas
- Contact with MDR-TB
- Poor adherence to current Tx
- Aged 25-45
- HIV co-infection
directly observed therapy in TB
People considered to be at high risk of poor adherence to Tx may have DOT – drug treatment is given under the observation of a key worker
TB - contact tracing
All household members and close contacts should be traced and assessed for latent/active TB
Casual contacts should be traced only if the person with TB is particularly infectious OR if casual contacts are at an increased risk of infection
MDR TB - Mx
Continue infection control measures until pulmonary / laryngeal disease has been excluded
Treat with at least 6 drugs to which it is sensitive
Latent TB - Mx
Treat with 3 months of Rifampicin and Isoniazid (with pyridoxine).
TB Drug Side Effects
Rifampicin
=> Abnormal LFTs, pink urine
Isoniazid
=> Peripheral neuropathy / encephalopathy
=> Very rare when prophylactic pyridoxine co-prescribed
Pyrazinamide:
=> Hepatotoxic (rare but severe)
Ethambutol
=> Optic neuritis – assess with colour vision testing
Non-pulmonary TB
haematogenous spread => some bacilli settle in specific organs and may remain dormant for many years – appearing later to cause disease.
Painless lymphadenopathy – Lymphatic TB
Monoarthritis – joint / spinal TB
Sterile pyuria – Renal TB
TB meningitis
Erythema nodosum / lupus vulgaris – cutaneous TB
TB pericarditis
What is Extrinsic Allergic Alveolitis ?
(AKA hypersensitivity pneumonitis)
= immune reactivity in the lungs due to inhaled antigens.
Can cause an acute type III hypersensitivity response with immune complex formation.
Or with repeated exposure there is a type IV cell mediated hypersensitivity reaction and granuloma formation.
The chronic inflammation eventually results in interstitial fibrosis.
Causes of extrinsic allergic alveolitis?
Farmer’s Lung
=> Caused by micopolyspora
Bird Fancier’s lung
=> Caused by proteins in bird droppings
Malt worker’s lung
=> Caused by aspergillus
extrinsic allergic alveolitis - presentation
Features of acute exposure come on 4-6 hours post-exposure.
=> Fevers, rigors and myalgia.
=> Dry cough and dyspnoea, possibly wheeze
Chronic features are as per idiopathic pulmonary fibrosis
Extrinsic allergic alveolitis - Ix
FBC – neutrophilia
Serum precipitant levels – only indicate exposure
CXR/CT/ lung function tests – confirm interstitial disease
Bronchoalveolar lavage – confirm diagnosis
=> Shows increased T lymphocytes and mast cells
Extrinsic Allergic Alveolitis - Mx
Aim for prevention, with no exposure/face masks/etc.
Long-term prednisolone may give physiological improvement
Established fibrosis cannot be treated.
Compensation available for patients with Farmer’s lung.
RFs for lung cancer
SMOKING is the most common risk factor (90% of cases). .
Other RFs:
- Passive smoking
- Urban living
- Occupational exposure (asbestos, etc.)
What are the types of lung cancer?
small cell disease (20%)
non-small cell disease (80%).
=> SCC; adenocarcinoma ; large cell anaplastic tumours
Lung cancer - SCC
NON-SMALL CELL
Arise from squamous metaplasia of the normally pseudostratified ciliated columnar epithelium, in response to cigarette smoke exposure.
They are usually central and close to the carina
=> Thus frequently present with collapse/infection secondary to obstruction.
May secrete PTH, causing hypercalcaemia.
=> (Beware as hypercalcaemia can also be due to bone mets)
They are relatively slow growing compared to other tumours, and may be resectable.
What is atelectasis?
What are the causes?
= partial collapse (or incomplete inflation) of a lung
OBSTRUCTIVE
=> mucous plug , foreign body, mass
OTHER
=> PTX, surfactant deficiency, scarring/fibrosis
Lung cancer - adenocarcinoma
NON-SMALL CELL
Equal gender incidence, and less related to smoking.
Characteristically originate in peripheral locations, potentially in areas of previous lung scarring.
(Bronchoalveolar carcinoma is a special type of adenocarcinoma)
Accounts for <5%, but a better prognosis.
Lung cancer - large cell anaplastic carcinoma
NON-SMALL CELL
Features showing SCC or adenocarcinomatous origins may be seen, but they are not differentiated enough to be classified.
Have a poor prognosis
Often widely disseminated at diagnosis.
Lung cancer - small cell carcinoma
AKA oat cell carcinoma (as the cell nuclei resemble oat grains).
Usually centrally located, and rapidly growing.
Most highly malignant of all lung cancers.
=> Often metastasised at diagnosis.
Originate from the bronchial epithelium, but differentiate into neuroendocrine cells to secrete active products (ADH / ACTH)
What paraneoplastic syndromes can be caused by hormone secretion from lung cancer?
ADH => symptoms of SIADH (i.e. dilutional hyponatraemia)
ACTH => Cushing’s syndrome
Hypertrophic pulmonary osteoarthropathy
Eaton Lambert Syndrome
Hyper PTH
Eaton Lambert Syndrome
Rare - sometimes seen in Pts with small cell lung cancer
Myasthenia Gravis-like symptoms
=> Proximal muscle weakness and reduced tendon reflexes.
=> Can be accompanied by dry eyes, sexual impotence and neuropathy.
!!! Symptoms get better with usage, unlike MG !!!
Lung cancer - presentation
Symptoms:
- Persistent cough (80%)
- Haemoptysis
- Dyspnoea
- Chest pain
- B-symptoms
O/E:
- Clubbing
- Cachexia
- Signs of anaemia
- Hypertrophic pulmonary osteoarthropathy
- Paraneoplastic syndrome – clubbing and painful peri-osteitis of small joints of the hand.
- Chest signs of collapse/consolidation/effusion
- Signs of metastases.
Lung cancer - Ix
FBC, LFTs, U&Es, calcium
CXR – ANY patient with haemoptysis should have a CXR
=> Symptomatic tumours are almost always visible.
=> A normal CXR in a symptomatic patient should warrant further Ix for central tumours.
Sputum/pleural fluid cytology
Staging CT – head to pelvis
Biopsy:
- CT guided if peripheral (risk of PTX)
- Via bronchoscopy if central.
Pulmonary function tests – useful if planning surgery
PET scan / radionucleotide bone scan – ?mets
Signs of local invasion of lung cancer
Recurrent laryngeal nerve palsy
=> Change in voice
=> If present, indicates inoperability.
Phrenic nerve palsy
SVC obstruction
Pancoast syndrome:
- Horner’s syndrome (miosis, ptosis, anhidrosis)
- Shoulder pain, radiating along ulnar forearm and into hand
- Atrophy of hand/arm muscles
- Oedema (due to blodd vessel compression)
Where does lung cancer most commonly metastasise to?
Brain,
Bone,
Liver
Adrenal gland
Non-small cell lung cancer - Mx
Surgical excision if peripheral enough, with no LNs/metastatic spread; with adjuvant chemotherapy.
=> Must be >2cm from carina.
Curative radiotherapy can be an alternative if poor respiratory reserve, with adjuvant chemotherapy.
Small cell lung cancer - Mx
Nearly always disseminated at presentation
May respond to chemotherapy +/- radiotherapy
May have prophylactic cranial radiotherapy
Obstructive Sleep Apnoea
= Interrupted and repeated collapse of the upper airway during REM sleep, associated with hypopnoea/apnoea and desaturations
Hypoxia leads to increasing respiratory effort, until the patient overcomes the resistance.
The combination of central hypoxia and respiratory effort briefly wakes the patient, leading to excessive daytime sleepiness.
The patient is unaware of the awakenings from sleep.
Correctible factors causing OSA
Respiratory Depressants
=> Opioids, alcohol, sedatives
Nasal Obstruction
=> Adenoids, rhinitis, polyps
Encroachment on the pharynx:
=> Obesity, acromegaly.
Obstructive Sleep Apnoea - presentation
Loud snoring during sleep
Daytime sleepiness
Morning headaches
Decreased libido
Nocturnal choking
Witnessed apnoeic episodes
Obstructive Sleep Apnoea - Ix
- Epsworth sleepiness Scale – to distinguish from simple snoring.
- Endoscopic examination of the upper airway by ENT
- Polysomnography = gold standard for diagnosis
=> Diagnostic, but rarely used.
Diagnosis is made with the occurrence of >15 episodes of apnoea/hypopnoea during one hour of sleep.
What is assessed in polysomnography?
Inpatient assessment of variable parameters (EEG, EMG, electro-oculogram, respiratory airflow, thoraco-abdominal movement, ECG, oximetry, snoring sound and video).
Obstructive sleep apnoea - Mx
Behavioural changes – allow partner to sleep first, sleep on side.
Weight reduction
Avoidance of alcohol and tobacco
CPAP via nasal mask = gold-standard management
=> Positive pressure keeps the airway open
=> 50% will not tolerate CPAP
Alternatives to CPAP include:
- Intra-oral devices
- Daytime stimulants – e.g. modafinol
- Upper airway surgery – if pressure assessments can localise a level of obstruction.
What is pneumoconiosis?
What is the pathophysiology behind it ?
= disease of the lungs caused by inhalation of dusts, generally used to refer to pathology caused by coal dust
The dust is toxic to macrophages (the normal defence for inhaled dusts) => INFLAMMATORY RESPONSE
If this becomes chronic, there will also be fibrosis leading to restrictive lung disease.
Simple Coalworker’s Pneumoconiosis
Presence of small nodules (2-5 mm) on CXR, not associated with any clinically significant impairment of respiratory function.
May develop to PMF.
Progressive Massive Fibrosis (PMF)
Presence of large nodules (>10mm) on CXR, and the disease progresses relentlessly, leading to a mixed obstructive and restrictive pattern.
May present long after active exposure to coal dust and culminates in COPD (often with black sputum)
Can progress to respiratory failure.
Compensation available to patients with PMF
Asbestos-related Lung Disease
- Asbestos Bodies
- Pleural Plaques, Effusion and Thickening
- Mesothelioma
- Asbestosis
There can be a latent period of up to 50 years between exposure and clinical onset of disease.
The risk of disease is proportionate to intensity of exposure
Asbestos bodies
Not pathological in themselves, merely act as a marker of asbestos exposure
Can only be seen histologically, following lung biopsy
=> stain golden brown, assuming the shape of fusiform or beaded rods with a translucent centre
Asbestos Pleural Plaques
Can occur after light exposure and are normally asymptomatic (may be associated with recurrent pleural effusions)
There may be mild restrictive deficit on spirometry, with pleural thickening and calcification on CXR
Locations most commonly encountered include posterolateral, mediastinal, and diaphragmatic pleura
More heavy exposure can cause diffuse pleural thickening (affecting >1/4 of the pleural surface), which will produce restrictive deficits
Asbestos-related Mesothelioma
Caused by light exposure
Interval of 20-40 years between exposure and disease onset.
Presentation:
- Pleuritic chest pain
- Increasing dyspnoea
- Unilateral pleural effusion on CXR
Survival is poor (median survival 2 years from diagnosis).
Asbestosis
Caused by heavy exposure
Interval of 5-10 years from exposure to disease.
Progressive dyspnoea
Diffuse bilateral streaky strikes on CXR with honeycombing
Outcome is poor – can progress after exposure ceases.
Compensation in asbsestos-related lung disease
Patients can claim occupational compensation for:
bilateral diffuse pleural thickening,
asbestosis,
mesothelioma
asbestos-related bronchial carcinoma.
Angiography
Contrast injected (usually via a catheter introduced into the femoral artery)
Fluouroscopy is then used to visualise the arterial system
Risks = contrast reaction, haematoma/ pseudoaneurysm/ AVF formation / arterial occlusion
CT / MR Angiography (CTA / MRA)
= now more commonly used to assess the arterial system
CTA => carotid/cerebral disease
MRA => thoracic, abdominal or limb disease
Primary Headache Disorders
Tension headache
Migraine
Cluster headache
Secondary Headache Syndromes
Raised ICP
Idiopathic intracranial HTN
HTN
Meningeal irritation (SAH/meningitis)
Post-traumatic
Giant cell arteritis
Sinusitis
Metabolic disturbances
Drugs (nitrates, vasoactive agents).
What is a tension headache?
Continuous, severe pressure felt bilaterally over the vertex, occiput and eyes.
=> Can be “band like” and of variable intensity.
Classically occurs every day and can persist for year/months
Standard analgesics are ineffective, and if used continuously may exacerbate the situation when their effects wear off (analgesic/rebound headache)
Few associated symptoms
Tension headaches - Mx
If episodic (<15 days/ month)
=> Paracetamol and aspirin/NSAIDs
=> Advise that can lead to a medication overuse headache.
If medications are being used on more than two days per week, consider preventative Tx
=> Low dose amitriptyline
=> 75mg initially, titrated upwards if partial response
Chronic tension headache is more difficult to treat
=> Reassurance, relaxation techniques
=> Addressing underlying stressors
=> Medication overuse headache and clinical depression should be ruled out/ treated.
What are cluster headaches?
Short-lived (30-120 mins) episodes of severe, unilateral pain; typically centred on one eye and come on very suddenly.
Associated with AUTONOMIC features on the affected side.
- Red eye
- Eye/nose watering
- Ptosis
- Vomiting
They may occur several times per day and be recurrent for several weeks/months before the disorder remits
Up to 20% will experience an aura; and some may have mild background pain between attacks
Alcohol is a common precipitant
Cluster headache - Mx
Exclude secondary causes, and other causes of eye pain (e.g. angle closure glaucoma).
S.C. (or nasal) triptan to take at the start of an attack
=> Home oxygen for use during the attack
=> At least 12L/min through a non-rebreather (unless COPD)
Oral triptans/oral analgesia not effective for acute attack
Prophylactic Tx = alcohol avoidance (and verapamil – off licence).
What can migraines be associated with?
menstruation
OCP use
physical exercise
alcohol
specific food groups (cheese, chocolate, Chinese, red wine, etc)
emotional states.
Migraines - pathogenesis
= poorly understood
Vasodilation after a period of vasoconstriction (aura phase) is thought to correlate with the onset of headache.
Many vasoactive peptides mediate this process.
Migraine headache presentation
Migraine headache= throbbing headache with anorexia, N&V, and photophobia is seen.
Begins locally and spreads bilaterally.
Aggravated by movement
Can last several hours/days
Neurological Exam is relatively normal
Subtypes of migraine
Classical Migraine with Aura
Migraine without aura (common migraine)
Opthalmoplegic Migraine
Hemiparetic/ facioplegic migraine
Classical Migraine with Aura
Starts with sense of ill health (several hours), followed by visual aura in the field of vision opposite to the side of headache.
Sensory aura symptoms are less common, speech disturbance is very rare.
Thereafter, the headache begins.
Migraine without aura (common migraine)
Classic visual/sensory aura is absent, however patients may feel non-specifically unwell prior to onset of headache.
Opthalmoplegic Migraine
Migraine + 3rd or 6th nerve palsy.
Hemiparetic/ facioplegic migraine
Hemiparetic = headache plus temporary hemiparesis.
Facioplegic = headache plus unilateral facial weakness
Migraine - Ix
Examine to r/o other differentials:
- Signs of focal neurology, raised ICP, meningism, temporal arteritis, retinal haemorrhage (SAH).
Headache diary:
- Assess frequency, severity of attacks, precipitants, and exacerbating/relieving factors.
Migraine - Acute Mx
1st line is PO NSAID or paracetamol, plus anti-emetic (e.g. metoclopramide).
Offer PO triptan (sumatriptan) if attacks are severe
- Taken ASAP at the start of symptoms
- Can be intranasal if vomiting prevents oral Tx.
- Avoid if IHD, uncontrolled HTN, coronary artery spasm.
Opioids should NOT be used.
Follow up – repeated unsuccessful triptan treatment is rare if the underlying diagnosis is actually migraine.
Migraine - preventative Tx
TRIGGER AVOIDANCE
Consider Tx if migraine attacks are causing significant disability (e.g. if >2/month).
Topiramate and Propranolol are 1st line
=> Propranolol in women of child-bearing age.
2nd Line = Amitriptyline/anticonvulsants if these aren’t successful/tolerated
Menstrual-related migraines can be treated with mefenamic acid from the first day of menses, throughout menstruation; or triptans started 2 days before expected menses.
COCP should be avoided in women with migraine with aura, however contraceptive methods that prevent menstruation can be tried.
Hemiplegic Migraine vs TIA
In TIAs, the maximum deficit is present immediately, and headache is unusual.
Idiopathic Intracranial HTN - cause and presentation
IIH is most common in young obese women
Symptoms and signs of raised ICP, but no mass lesion on imaging.
It is thought to be a disorder of CSF reabsorption.
Most common presentation = visual disturbances (diplopia/obscuration) and headaches.
=> Sometimes associated with pulsatile tinnitus and 6th nerve palsy.
O/E: bilateral papilloedema.
Idiopathic Intracranial HTN - Ix
CT/MRI will be normal
LP will confirm increased CSF pressure.
Idiopathic Intracranial HTN - Mx
Weight loss may facilitate spontaneous remission.
A trial of corticosteroids may be successful
Definitive Mx is a surgical shunt (necessary to prevent optic atrophy due to prolonged raised pressure).
Trigeminal Neuralgia - cause and presentation
Compression / pathology (MS) of the trigeminal nerve root.
Agonising, sharp pain over the distribution of the nerve on one side, lasting only seconds.
Often with a sensory trigger from a certain point
Trigeminal Neuralgia - O/E
Look for any localising CNS signs, but examination usually normal.
trigeminal neuralgia vs. post-herpetic neuralgia
post-herpetic neuralgia
- pain is usually less severe and associated with itching/sensory changes.
- patient will have had shingles previously
Trigeminal Neuralgia - Mx
Simple analgesics are ineffective
Carbamazepine offers good symptom control
Sometimes TCAs (e.g. amitryptiline used)
Atypical Facial Pain
Episodic aching in non-anatomical distributions of the head/neck.
Commonly associated with depression/anxiety.
May respond to antidepressants.
What is Bulbar Palsy?
What are common and rarer causes?
= LMN weakness of muscles supplied by cranial nerves with cell bodies in the medulla (i.e. the “bulb”)
=> CN IX, X and XII
Most commonly degenerative (MND) or vascular (stroke) in origin.
More rare causes are inflammatory (Guillain-Barre), infective (botulism), neoplastic (brainstem tumours) or congenital.
Examination findings in Bulbar Palsy
Inspect the tongue – wasted, flaccid and fasciculation, can be moved rapidly.
Ask about dysphagia (do not test unless controlled environment)
Ask the patient to say “AHHH” – look for poor elevation of the soft palate.
Ask the patient to repeat sentences – quiet, nasal speech
Assess jaw jerk/gag reflex – may be absent.
Pseudobulbar Palsy
= Bilateral UMN disease of the medullary cranial nerves.
Most common causes are degenerative (MND) and vascular (stroke).
Also seen in MS and can follow head trauma.
Examination findings in pseudobulbar palsy
Inspect the tongue – stiff/spastic tongue with slow movements, not wasted.
Ask about dysphagia
Ask the patient to say “AHHH” – normal elevation of the soft palate.
Ask the patients to repeat sentences – gravelly, “Donald duck” speech
Assess jaw jerk/gag reflex – preserved, may be exaggerated jaw jerk.
May be mood disturbances
Cerebral hemisphere lesions
Cerebral lesions lead to impairment in higher function – the type of function affected gives clues to the location affected.
FRONTAL
- Intellectual impairment, personality change, urinary incontinence and monoparesis/hemiparesis.
- Broca’s aphasia (if left frontal area).
LEFT TEMPORO-PARIETAL (dominant hemisphere):
- Agraphia, alexia, acalculia
- Wernicke’s aphasia
- Contralateral sensory neglect
RIGHT TEMPORO-PARIETAL:
- Failure of face recognition
- Contralateral sensory neglect.
OCCIPITAL:
- Visual field defects
- Visuospatial defects
Lateral cerebellar lesions
cause IPSILATERAL pathological signs
Broad, ataxic gait
Titubation – rhythmic head tremor
Dysarthria - Slurred, staccato speech
Nystagmus - Course and horizontal, towards the side of the lesion
Hypotonia
Mild hyporeflexia
Dysmetria – imprecise movements/coordination
=> Finger to nose test – misses target, may be intention tremor which worsens as the patient approaches the target.
Dysdiadochokinesis – clumsy rapid alternating movements
How to assess for cerebellar dysarthria
Ask the patient to repeat “British constitution” / “baby hippopotamus”
Staccato speech - each syllable will be pronounced individually
Cerebellar exam - DANISH
- Dysdiadochokinesia
- Ataxia (gait and posture)
- Nystagmus
- Intention tremor
- Slurred, staccato speech
- Hypotonia/heel-shin test
To complete cerebellar examination – perform a full neurological examination of the CNS and PNS.
Midline Cerebellar lesions
Rolling, broad ataxic gait
Difficulty standing and sitting unsupported
=> Cannot perform Romberg’s test with eyes open or closed
=> Ask the patient to sit forward with arms across their chest.
Vertigo and vomiting if extension into fourth ventricle.
Common causes of Cerebellar Dysfunction
BILATERAL
Alcohol
Drugs – phenytoin, anti-epileptics
Paraneoplastic cerebellar degeneration
UNILATERAL
MS
Stroke
Tumour
=> Especially acoustic neuroma, meningioma
What investigation is useful in ?Paraneoplastic cerebellar degeneration
Anti-neuronal antibodies = +ve
Basal Ganglion Lesion - signs
Bradykinesia (can progress to akinesia)
Muscle rigidity
Involuntary movements
- Tremor
- Dystonia – spasms/abnormal muscle contractions
- Athetosis – writhing involuntary movements of hands/face/tongue
- Chorea – jerky involuntary movements
- Hemiballismus – violent involuntary movements, restricted to proximal muscles of one arm
What is meningitis?
= inflammation of the leptomeninges (i.e. the arachnoid and pia mater, and underlying CSF).
causes of meningitis
Outside of the neonatal period, 70% of acute bacterial meningitis cases are caused by:
Neisseria meningitidis
Streptococcus pneumoniae
Other:
- Listeria monocytogenes – common in the elderly/immunosuppressed
- Haemophilus influenzae
- Staph aureus
- TB
- Viral causes: Enteroviruses, HSV, VZV
- Fungal causes (in immunosuppressed patients)
TB Meningitis
Most commonly caused by blood-borne spread of M. tuberculosis to the brain following primary infection or miliary TB
RFs – immunosuppression, malnourishment, multiple comorbidities, recent contact with TB
May present as per acute bacterial meningitis, but more commonly as an insidious illness with fever, weight loss, and progressive confusion/cerebral irritation, eventually leading to coma
Meningitis - Routes of Infection
Blood-borne
Para-meningeal suppuration
=> e.g. otitis media, sinusitis
Direct spread through a defect in the dura
=> e.g. post-surgery, trauma
=> CSF leaking out of the nose/ear is a sign of a defect in the dura
Direct spread through the cribriform plate
=> rare
Meningitis - Presentation
Meningitic syndrome Triad:
1. Headache
2. Neck stiffness
3. Fever (+/- rigors)
Other symptoms include:
- Photophobia
- Vomiting
- Intense malaise (coming on over hours)
- Confusion / altered mental state
- Seizures
O/E:
- Kernig’s Sign positive
- Brudzinski’s sign positive
- Signs of raised ICP and/or cranial nerve palsies
In uncomplicated meningitis, consciousness will remain intact
Positive Kernig’s Sign
Flex the hip and knee
extending the knee causes pain
Positive Brudzinski’s sign
Passive flexion of the neck leads to flexion of the knees/hip
What symptoms may indicate complications in meningitis?
What are possible complications ?
Progressive drowsiness, lateralising signs or cranial nerve lesions
- Venous sinus thrombosis
- Severe cerebral oedema
- Hydrocephalus
Suspected meningitis - investigations
Bloods:
- FBC, U&E, clotting, glucose, lactate
- Cultures (prior to ABX if possible, but do not delay).
Serum PCR for pneumococcal and meningococcal antigens
LP – if no clinical suspicion of mass lesion / raised ICP
- Send for MCS, protein, glucose and meningococcal / pneumococcal viral PCR
- Do not delay LP unless signs of raised ICP
CT prior to LP – if ?raised ICP
Throat swabs – 1 for virology, 1 for bacteriology.
What causative pathogens may be suggested by CSF staining?
Gram positive intracellular diplococci = pneumococcus
Gram negative cocci = meningococcus.
Ziehl-Neelsen stain for acid-fast bacilli = TB
Indian Ink = fungi
CSF Findings - Bacterial Meningitis
Leucocytes - VERY HIGH
Protein - HIGH
Glucose - LOW (normal = 50-80% of blood level)
CSF findings - viral meningitis
Leucocytes - SLIGHTLY RAISED
Protein - SLIGHTLY RAISED
Glucose - NORMAL (normal = 50-80% of blood level)
Appearance = yellow/turbid
CSF findings - Viral Meningitis
Leucocytes - SLIGHTLY RAISED
Protein - SLIGHTLY RAISED
Glucose - NORMAL (normal = 50-80% of blood level)
Appearance = clear
CSF Findings - TB meningitis
Leucocytes - RAISED
Protein - RAISED
Glucose - VERY LOW (normal = 50-80% of blood level)
Appearance = yellow/viscous
Meningitis - Mx
If meningitis is suspected => LP within 1 hour
If this cannot be achieved, empirical ABX should be given immediately after blood cultures.
Meningitis is managed with:
* Antibiotics
* Adequate oxygenation
* Prevention of hypoglycaemia and hyponatraemia
* Anticonvulsants – if patient is fitting
* Decrease intracranial hypertension – prevent brain herniation
* Notifiable Disease – inform public health of ALL cases.
Meningitis - empirical Tx
If non-blanching rash:
=> Benzylpenicillin 1.2g IM
=> 2.4mg 4-hourly is then the treatment of choice in hospital
=> Cefotaxime can be used in penicillin allergic patients
If <60 and not immunosuppressed:
=> IV ceftriazone 2g BD (IV chloramphenicol in penicillin allergic patients)
=> IV dexamethasone given with 1st dose of ABX and 2nd dose after 6 hours
If >60 or immunosuppressed:
- IV ceftriaxone 2g BD
- IV amoxicillin 2g 4-hourly
- IV dexamethasone
Add IV acyclovir if ?HSV encephalitis (i.e. if drowsy, mood changes)
Meningitis - treatment for contacts
Meningococcal meningitis contacts:
=> Single dose of ciprofloxacin given to all close contacts as prophylaxis.
What is encephalitis?
= inflammation of the brain parenchyma, usually viral (similar organisms to viral meningitis).
HSV-1 => causes necrotising encephalitis, affecting the temporal lobes.
HSV-2 => causes meningitis in adults
Encephalitis - clinical features
Normally mild
=> Headache, drowsiness, fever, malaise and confusion.
Rarely, serious illness can occur:
=> High fever, mood changes, progressive drowsiness over hours/days; leading to seizures and coma
=> Most commonly caused by HSV-1
=> Carries a mortality of 20%
Encephalitis - Ix
Head CT/MRI
=> Diffuse oedema, classically in the temporal lobes
Lumbar puncture:
=> Raised opening pressure, Raised lymphocytes, Raised protein
=> Normal glucose
=> Positive viral PCR
Viral serology:
=> Blood and CSF culture
HSV Encephalitis
Clinical features as for viral encephalitis
CSF PCR = diagnostic
Mx = IV acyclovir for >10 days
Mortality = 20%
Complications of bacterial meningitis
ACUTE:
- Sepsis
- DIC
- Hydrocephalus
- Adrenal haemorrhage (Waterhouse-Friedrichsen syndrome)
LONGER-TERM:
- Brain abscesses
- Seizure disorders
- CN palsies – sensorineural hearing loss or gaze palsies
- Ataxia / muscular hypotonia
Long-term sequelae are most common in pneumococcal meningitis
Brain Abscess
Generally very rare, most commonly complicating otitis media/paranasal sinus infections or secondary to bacterial endocarditis.
May be a Hx of head trauma/neurosurgery
Presentation:
- Features of expanding mass lesion
- Fever
- Possible systemic illness
Brain Abscess - Mx
Surgical drainage
Broad-spectrum ABX
High dose corticosteroids
Mortality is high; and many of those who survive go on to develop epilepsy.
Epidural Spinal Abscess
Presents with fever, back pain and later spinal root lesions
Caused by S. aureus
Requires emergency imaging, ABX and surgical decompression
What is epilepsy?
= the continuing tendency to have recurrent, unprovoked seizures.
Types of Seizure
- Generalised:
- Tonic clonic
- Absence
- Myoclonic
- Tonic
- Atonic - Focal:
- Temporal
- Frontal
- Occipital
- Parietal
Generalised seizures
- Discharge from both hemispheres
- No warning
- Always have LOC
Focal seizures
- Discharge from ONE part of ONE hemisphere
- May have a preceding aura
- May or may not have LOC
- May lead to generalised tonic-clonic seizure if LOC
Tonic clonic seizure
TONIC PHASE
- body becomes rigid for up to a minute, usually fall to the ground
- Accompanied by tongue biting and incontinence
- holds breath (cyanosis)
CLONIC PHASE
- lasts seconds to minutes
- rhythmical jerking
- irregular breathing, cyanosis, salivation
- tongue biting, incontinence
POST-ICTAL PHASE
- drowsiness/ sleep / LoC (up to several hours)
Absence seizure
“blanking out” / staring
Absence of motor symptoms
Brief onset and termination
Myoclonic seizure
repetitive, jerky movements
Tonic seizure
generalised increase in tone => fall
Atonic seizure
loss of muscle tone => fall
Temporal seizure (focal)
Aura - fear/deja vu sensation
Smell / taste / sound distortions
Lip smacking / chewing
Frontal seizure (focal)
Clonic movements spread proximally
Occipital seizure (focal)
Visual disturbances
Parietal seizure (focal)
Contralateral sensory disturbance
Tingling/numbness
Todd’s paresis.
= when focal seizures are associated with temporary paresis of the originally affected limb after the attack
Epileptic vs non-epileptic seizures
EPILEPTIC = Seizure due to excessive, hyper-synchronous neuronal discharge in the cerebral cortex
NON-EPILEPTIC = Seizures not involving abnormal electrical activity in the brain
Dissociative Seizures
a type of non-epileptic seizure
Caused by mental or emotional processes, rather than by a physical cause.
=> E.g. Seizure can happen as a cut-off mechanism to prevent bad memories being relived.
Often caused by traumatic events
- Such as major accidents, bereavement, psychological stress (e.g. divorce), physical or sexual abuse, bullying.
Seizures - Investigations
- History = MOST IMPORTANT
- Frequency, triggers, length, symptoms
- Any impairments, educational/psychological/social impacts
- Video of seizure if possible - Examination:
- CNS and PNS
- CVS and resp
- Skin markers for neurocutaneous syndromes - EEG
- Can show neuronal excitability in epilepsy (sharp waves/complexes).
- NB – may be normal in epilepsy or abnormal in non-epilepsy
- If normal, consider sleep-deprived EEG/24hr ambulatory - Imaging
- MRI/CT – if neuro signs between seizures (r/o tumour or CVD)
- PET/SPECT – detect areas of hypo/hypermetabolism - Tests to r/o other causes
- ECG – cardiac causes
- Bloods – metabolic disturbances
- FBC, U&Es, LFTs, Ca, Mg, glucose.
- Toxicology/drug screen if indicated.
Generalised seizures - immediate management
Most seizures will only last a few minutes and end spontaneously – best immediate management:
- Place the patient in the recovery position
- Remove harmful objects around them
If the seizure lasts over 3 minutes, or starts outside of hospital and is still ongoing once in hospital – treat as status epilepticus:
- ABCDE
=> 100% oxygen, IV access, bloods including glucose, magnesium and calcium, VBG/ABG, ECG.
=> If hypoglycaemia, give IV glucose.
=> If any suspicion of alcohol withdrawal, give IV pabrinex.
IV/PR/SL Lorazepam
=> 2-4mg bolus, repeated after 5 mins if no response.
In females of childbearing age, perform pregnancy test.
If seizure is continuing despite x2 doses of lorazepam – initiate 2nd anti-convulsant.
=> Often IV phenytoin 15mg/kg slow infusion with continuous ECG monitoring.
If seizure is continuing 20 minutes from first presentation, then ICU should be called.
=> They may choose to intubate under GA.
=> Thiopentone = agent of choice.
Long-term management of epilepsy
TRIGGER AVOIDANCE = VERY IMPORTANT
=> Common triggers are lack of sleep, alcohol/drugs, hypoglycaemia, caffeine, stress, flashing lights.
Most specialists will start AED treatment after 2 seizures, after ruling out organic causes.
Drug depends on type of seizure:
GENERALISED:
- 1st line is valproate (or Lamotrigine in females of child-bearing age).
- Adjuncts may be clobazam, carbamazepine or Levetiracetam
- Ethosuximide is generally 1st line for Absence seizures.
FOCAL:
- 1st line is Carbamazepine (or Lamotrigine in females of child-bearing age).
- Multiple adjuncts are used.
Withdrawal from anti-epileptic medications
Withdrawal from AEDs may be considered if Pt is seizure free for 2-4 years.
Drug should be dose-reduced every 4 weeks
Patient has to stop driving for the withdrawal.
Sodium valproate - SEs
Weight gain
Hair loss
Teratogenic
Carbamazepine - SEs
Agranulocytosis
Teratogenic
CYP140 inducer
Hyponatraemia
Phenytoin - SEs
Increased gum growth
Nystagmus
Enzyme inducer
Zero order kinetics, thus requires TDM
Pregnancy and AEDs
Ideally patients should withdraw from AEDs if possible prior to conception.
However, treatment is preferable to hypoxic seizures during pregnancy
Carbamazepine, Valproate, and Phenytoin all lead to NTDs (although carbamazepine has the lowest risk of the 3)
Lamotrigine is now 1st line in a woman of child-bearing age and in pregnancy for generalised seizures.
Any drug should be given with 5mg folic acid daily in the 1st trimester and vitamin K in the 3rd trimester (due to risk of neonatal bleeding).
Driving laws for seizures / epilepsy
Patients must tell the DVLA immediately and stop driving if they have had a seizure.
If the attack was whilst awake and involved LOC, the license will be revoked.
Patients can apply for their license back if they haven’t had a seizure for 6 months (after one seizure)
After repeated attacks (true epilepsy), you can reapply after 1 year being seizure free.
Patients with sleep-related epilepsy can drive if they have only had seizures while sleeping during the past 3 years.
What features are required for a diagnosis of dementia?
- Evidence of memory loss
- At least one of:
* Language impairment
* Impaired executive function (e.g. problem solving, emotions).
* Apraxia (difficulty motor planning)
* Agnosia (difficulty recognising objects) - No other medical or psychiatric explanation
- Present for at least 6 months
What is Mild Cognitive Impairment ?
= evidence of early memory decline on formal memory tests (e.g. MMSE) without clinical evidence of the other features of dementia.
Types of Dementia
- Alzheimer’s Disease – 2/3rd
- Vascular Dementia – 20%
- Lewy Body Dementia – 5%
- Frontotemporal Dementia – 2%
- Other rarer causes
Alzheimer’s Disease - pathology
Characteristic beta-amyloid plaques and neurofibrillary tangles.
Brain atrophy, particularly the hippocampus.
Enlarged ventricles
Tends to be a gradual, progressive decline.
Alzheimer’s Disease - presentation
= Progressive memory loss that affects function.
- Forgets names, people, places
- Repeat themselves
- Cannot remember new info
- Misplace items
- Confusion about time of day
- Problems finding words
- Mood/behaviour problems
Causes of Alzheimer’s Disease
Early onset (<65) there is some familial risk
Association with APO-E gene
Association with CVD risk factors.
Vascular Dementia - pathophysiology
= 2nd most common type of dementia.
Caused by reduced blood supply to the brain
=> Due to diseased blood vessels
Usually stepwise progression
=> Stable and then sudden decline – e.g. after a stroke.
Risk factors – HTN, cholesterol, alcohol, smoking, DM, male, etc.
Vascular Dementia - symptoms
= problems with memory, thinking and reasoning.
Problems planning/organising/decision making/problem solving.
Difficulty following steps/instructions
Slower thought speed
(Often overlaps with symptoms of Alzheimer’s)
Lewy-Body Dementia - pathophysiology
Characterised by alpha-synuclein deposits in the brain.
Cause is unknown.
Lewy-Body Dementia - symptoms
Early stages – hallucinations and delusions, mood swings/ short tempered, short attention span, fluctuating alertness.
Late stages – Motor deterioration, similar to Parkinson’s.
Fronto-temporal dementia - symptoms
Different Variants:
- Behavioural (2/3)
- Progressive non-fluent aphasia
- Semantic dementia
Symptoms of behavioural variant:
- Loss of inhibition – rude and compulsive
- Personality changes – loss of interest in people, loss of sympapthy/empathy
- Crave food – often sweet/fatty, eat until vomit.
- Speech, language difficulties
- (A cognitive deficit is not so obvious).
What are some rarer causes of dementia?
- Wernicke-Korsakoff Syndrome
- Down’s Syndrome
- Huntington’s
- Multiple Sclerosis
- Parkinson’s Disease Dementia
- Creuzfeldt-Jakob disease
- Pugilistic Dementia (repetitive head trauma).
Dementia - Investigations
Detailed History (often collateral)
=> Duration of Sx, effects on ADLs
=> r/o dementia mimics – e.g. delirium/depression
Physical examination
=> CNS/PNS, gait, CVS, thyroid.
Blood tests +/- lumbar puncture
=> “Confusion bloods” = FBC, CRP, U&E, LFT, TFT, glucose, calcium, B12, folate.
Medication Review
=> Look for any correlation of medications and duration of symptoms
Cognitive tests – e.g. MMSE/MOCA
CT/MRI
=> To exclude other causes.
“Confusion bloods”
= FBC, CRP, U&E, LFT, TFT, glucose, calcium, B12, folate.
Dementia - Management
There is NO CURE – eventually progresses to dependence and palliative care.
- Referral to Psychiatric Services
=> Memory clinic, Rapid response Liaison Psychiatry (RRLP) - Pharmacological – alleviate symptoms/slow progression
- Non-pharmacological
- Social services care plan
- OT input
- Consider capacity – organise ADs/LPAs/DNACPRs while the patient still has capacity.
- Cognitive Stimulation Therapy – may slow decline.
Dementia - pharmacological management options
Cholinesterase Inhibitors – e.g. donepezil, rivastigmine, galantamine.
=> Alzheimer’s, LBD and Parkinson’s (mild-moderate disease).
NMDA Receptor Antagonists – e.g. Memantine
=> Alzheimer’s only (moderate-severe disease).
NB – there is no treatment for vascular/FT dementia.
For behavioural/psychological symptoms, consider – anti-depressants, antipsychotics, laxatives, analgesia.
Driving rules for patients on insulin
can drive a car as long as they have hypoglycaemic awareness, not more than one episode of hypoglycaemia requiring the assistance of another person within the preceding 12 months and no relevant visual impairment.
They are required to check their blood glucose levels every 2 hours when driving.
