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
