KCP Flashcards
Why are women advised to take folic acid during pregnancy?
Has been shown to reduce neural tube defects.
Closure of the neural tube requires rapid proliferation of neuroepithelial cells, which requires amino acids, supplied by folic acid.
What are the effects of foetal alcohol syndrome?
Facial dysmorphism is common, such as low nasal bridge, thin upper lip, smooth philtrum and small palpebral fissures.
Irreversible nervous system effects.
Low birth weight
Intellectual difficulties
How much alcohol should a pregnant women consume?
Max 1 unit a week, but ideally none.
What are the features of mothers in higher-risk pregnancies?
Women with epilepsy, diabetes, congenital cardiac disease, autoimmune disorders, obesity or mental illness.
What is the ideal diet of a pregnant women?
- Eat fruit, vegetables, starchy foods, protein and dairy.
- Should avoid foods such as soft mould cheeses, pate, raw shellfish, liver products and cured meat
- Vegetarians and vegans are at risk of nutritional deficiency.
- Cut down on caffeine before pregnancy to less than 300mg daily.
- do not take Vit A
What supplements should be taken during pregnancy?
Make sure Vit D levels and calcium levels are adequate as well as iron levels.
400 micrograms of folic acid should be taken daily from trying to conceive to 12 weeks in pregnancy
What are the risks with being an older mother?
- Older mothers have higher cases of miscarriage, medical comorbidity and maternal/foetal mortality.
- Risks of diseases such as obesity, diabetes and heart disease increase with age.
- Older women need C-sections more often due to poorer uterine contractibility.
What is methotrexate and can it be used in pregnancy?
Treatment for rheumatoid arthritis. It is a competitive inhibitor of DHF, which causes a decrease in cell division and amino acid synthesis.
Should be off methotrexate for 3 months before conception and during pregnancy. Safe DMARDs are a replacement option
What is sodium valoproate and can it be used in pregnancy?
Used to treat epilepsy
Can cause neural tube-like defects and associated with cardial, oral and urogenital malformations. Must not be used in women or girls of child-bearing age unless in a Pregnancy Prevention Programme.
What drugs should be avoided during pregnancy?
- methotrexate (0-14 days)
- sodium valporate
- Cytotoxic drugs, eg chemotherapy
- Retinoids used in acne
- Warfarin (especially first trimester)
- ACE inhibitors
- statins
- certain antibiotics, eg tetracyclines Sulfonamides
What are ACE inhibitors and angiotensin receptor blockers and can they be used in pregnancy?
ACEi and ARBs are used for treatment for hypertension, heart failure, and renal disease.
Stop for any duration of pregnancy and during conceiving
May reduce placental blood flow- reduced foetal growth, reduced amniotic fluid, foetal renal damage, low blood pressure.
What are NSAIDs and can they be used during pregnancy?
Medication used to reduced inflammation, can cause premature closure of the ductus arterious, which leads to pulmonary hypertension, Cardiac failure and Foetal hydrops (fluid accumulation in tissues and organs)
What is the ductus arteriosus in a foetus and what can NSAIDs do to it?
The DA enables oxygenated blood to pass from the pulmonary artery to aorta, bypassing the lung. The blood vessel is kept open by prostaglandin E (after birth levels drop and it closes). NSAIDs stop PRE being produced, resulting in a premature closing of the DA
What topics should be discussed in a pre-conception counselling?
GP should ask about occupation (exposures), diet (vegan?), health conditions, smoking, alcohol intake, exercise, attempts to get pregnancy, previous pregnancies, family history, current medications.
What are some foetal neural tube defects?
Birth defects of the brain, spine and spinal cord Spina bifida (neural tube does not close properly)
Does pregnancy impact pharmokinetics?
Yes, effects metabolism and excretion rates. important to monitor drug levels to ensure there is maternal or foetal toxicity
Should pregnant women take over the counter drugs?
Consult doctor before taking them.
Stay away from NSAIDs eg ibuprofen
Paracetamol is safe
What stages of foetal development are different parts of the body effected?
What is the microbiome and what roles does the microbiome have in weight?
The microbiome is the bacteria, fungi and viruses that colonise the body. The gut, skin and vagina all have their own microbiome.
Two common gutmicrobes are bacteroidetes and firmicutes. Firmicutes generate more harvestable energy, and are more common in obese people.
F/B ratio important, high= obesity, low= inflammatory bowel disease
What are risk factors for type 2 diabetes?
- Being overweight/obesity
- age
- low social-economic status
- sedentary lifestyle
- unhealthy diet choices
- cigarette smoking
- genetic ancestry
- family history of type 2 diabetes
- psychosocial stress and depression
What are the symptoms and diagnosis techniques for Diabetes mellitus?
Symptoms of hyperglycemia are polyuria, polydipsia and thirst. Other symptoms are fatigue, recurrent infections and weight loss (for type 1).
Random plasma glucose or after a 75g glucose load > 11.1 mmol/L, a fasting plasma glucose > 7 mmol or haemoglobin A1c > 48 mmol/mol. In asymptomatic patients need two investigations separated in time.
What is Haemoglobin A1C-glycated haemoglobin and why is it important in diabetes?
In diabetes, attachment of glucose to haemoglobin increases the amount in the HbA1 (glycated Hb) and the fraction of HbA1 to HbA0 (non-glycated) can be separated by chromatography. This can help diagnose diabetes
Normal range is 20-42 mmol/mol
Important to rememberthat HbAlc takes time to be elevated as red blood cells live for 3 months.
What are the differences in type 1 and type 2 diabetes?
What is the pathophysiology of type 1 diabetes?
A T-cell mediated autoimmune disease involving destruction of the beta cells in the pancreatic islets. Susceptible individuals who are exposed to a environmental trigger then developed β-cell autoimmunity that led to progressive loss of β cells. This process was seen to take place over a prolonged period.
The pathology in the pre-diabetic pancreas is characterised by an inflammatory lesion within islets, ‘insulitis’, with infiltration of the islets by mononuclear cells containing activated macrophages, helper cytotoxic and suppressor T lymphocytes, natural killer cells and B lymphocytes.
This leads to the beta cells no longer producing and excreting insulin around the body.
What is the pathophysiology of type 2 diabetes?
The primary cause of insulin resistance remains unclear, one theory is intra-abdominal ‘central’ adipose tissue (which is metabolically active) and releases large quantities of free fatty acids, which may induce insulin resistance because they compete with glucose as a fuel supply for oxidation in peripheral tissues such as muscles
What is the treatment for type 1 diabetes?
Requires insulin therapy.
Common to have a basal long-acting insulin combined with meal insulin boluses of short-acting insulin (basal-bolus). Continuous subcutaneous insulin pumps can also be used.
What is the treatment for type 2 diabetes?
Lifestyle advice, nutritional advice and weight loss advice.
Exercise, stop smoking and reduce alcohol.
Other drug treatments are metformin which sensitises insulin action and opposes action of glucagon and causes increased glucose uptake by muscle. It causes weight loss and the most common side effect is GI upset.
Other drugs are also used:
What are the complications of having diabetes?
- hypertension
- cardiovascular disease
- kidney disease
- retinopathy
- neuropathy
- increased risk of infections
What is the anatomy of the pancreas?
The normal adult pancreas contains about 1 million islets of langerhans. The core of each islet consists of β cells that produce insulin, and is surrounded by a cortex of other cells such as alpha cells (produce glucagon)
What is the significance of urine and blood ketones in diabetes?
Ketonuria (high levels of ketone in your urine) may be found in people who have been fasting or exercising strenuously for long periods, vomiting repeatedly, or eating a diet high in fat and low in carbohydrate.
Ketonuria is therefore not pathognomonic of diabetes but, if it is associated with glycosuria (glucose in the urine), the diagnosis of diabetes is highly likely
Measured in a lab
What is the clinical presentation of type 1 diabetes?
Polyuria (excessive urination), polydipsia (excessive thirst), and polyphagia (excessive eating), along with exhaustion, nausea, and blurred vision
What is the islet autoantibody test?
A blood test
Islet autoantibodies are markers that appear when insulin producing beta cells in pancreas are damaged.
Used to tell difference between type 1 (positive) and type 2 (will be negative)
What is the negative feedback loop pf glucose control?
What is health screening?
Tests of a healthy population to identify risk factors or early stages of disease.
It is different to using a test for diagnosis even if it is the same test
What are features of a good screening test?
- Simple
- Inexpensive
- Widely available
- Reliable (minimal false positives and negatives)
- Minimal discomfort
- There is a treatment for the disease being screened
- It will lead to improved health outcomes
What are the risks of health screening?
False reassurance with false negatives
Anxiety caused by false positives
Complications from follow up investigations
Overdiagnosis
What is overdiagnosis?
Where disease that would not have caused harm to people in their lifetime is detected.
More resources are used to treat the disease when it may not have shortened life expectancy.
What are the feastures of breast screening in the UK?
For women aged 50-70, every 3 years
Screening is a mammogram
Two views are taken- takes around 20-30mins.
What are the risk factors for breast cancer?
- Family history
- Obestiy post-menopause
- alcohol
- HRT
- inactivity
- Early pubery and late menopause (increased expsoure to oestrogen)
What reduces risk of breast cancer?
Pregnancy, especially an earlier one
Breast feeding
What is the clinical signs of breast cancer?
Lump in the breast
Skin changes
Lump or swelling in armpits
Change in appearance of nipple
Lymphadenopathy (changes in lymph nodes)
What are the conponents of a triple assessment done to a patient with suspected breast cancer?
What are the different treatment methods in treating breast cancer?
What are the main principles of breast cancer surgery?
Main principle is to do the least possible
Remove tumour with a margin of at least 1mm or normal tissue.
What are the main adjuvant therapies used in breast cancer?
Can give local radiotherapy
Chemotherapy
Can use drugs such as Trastuzumab-monoclonal antibody for HER2 positive patients or aromatase inhibitors for hormone receptor postive cancer.
What are common causes of breathlessness?
- Asthma
- COPD
- Heart failure
- Anaemia
- Bronchiectasis (widening of airways)
- Idiopathic pulmonary fibrosis
What components is the total lung volume made of?
Inspiratory reserve volume
Tidal volume
Expiratory reserve volume
Residual volume
How can asthma be diagnosed?
Using a spirometery whilst normal, and then repeating the test after taking a beta-agonist
What are FEV1 and FVC?
FEV1= the amount of air that can be breathed out in 1s
FVC= forced vital capacity, the volume of the lung
What will a spirometery graph look like for a normal, COPD and asthmatic patient?
What is the fractional exhaled nitric oxide test?
Used to diagnose asthma
Asthma is an autoimmune respiratory disease which causes airway inflammation; nitric oxide is produced by respiratory epithelium in response to inflammation
Can be measured in exhaled breath
Does not work in smokers
What is the treatment for asthma?
Smoking cessation, including those around you
Allergen avoidance
Weight loss
Reliever= beta-2 agonist
Preventer= inhaled corticosteroid
What is heart failure due to?
Due to impaired ability to fill or eject blood
What is atrial nutriuretic peptide?
It is released from the atria in response to stretch, this would occur with fluid overload (with LV is not ejecting enough blood, which increases pressure and stretch in LA)
Can be detected
Has a wide range of effects such as natriuresis (sodium loss through kidney), diuesis and lower blood pressure.
What are the biomarkers of heart failure?
Atrial natriuetic peptide
Brain-type natriuertic peptide
How is heart failure diagnosed?
Detected by presence of biomarkers
If these are elevated, confirmed by echocardiology
What does the echocardiology measure?
Compares the amount of blood in the ventricle before and after each contraction.
What is and what causes finger clubbing?
FINGER CLUBBING= increase in distal finger size, loss of nail bed angle, increased nail curvature
CAUSES= disease of the heart or lungs which cause chronically low blood levels of oxygen. Diseases which cause malabsorption, such as cystic fibrosis or celiac disease can also cause clubbing
What is cyanosis?
A bluish discolouration of skin or mucous membranes.
Caused by an increasenin concentration of deoxyhaemoglobin
Harder to see in dark skin tones- measured oxygen saturation much more reliable
What is the pathology of idiopathic pulmonary fibrosis?
It is a chronic, progressive fibrotic disorder.
Proliferation of mesenchymal cells causes increased production and deposition of disorganised collagen
Causes a stiffness of lungs and loss of normal alveolar-capillary interface
This causes V/Q mismatch and hypoxaemia
How is pulmonary fibrosis diagnosed?
Diagnosed by x-ray, CT chest scan and pulmonary function tests
In x-ray, diagnosed by shaggy and hard to spot edges of the lungs
Has a reduced FEV1/FVC ratio
What causes acute breathless?
Acute pulmonary oedema
Acute asthma or COPD
Pneumothroax
Pneumonia
Metabolic acidosis
Causes of a cough?
Asthma
Allergies
Cold, flu and pneumonia
COPD
pulomary fibrosis
Lung cancer
Common causes of haemoptysis?
Lung cancer
Pneumonia
bronchitis
Tuberculosis
What is the pathophysiology of asthma?
A chronic inflammatory disorder of the airway which is associated with airway hyper-responsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness and coughing, particularly at night and in the early morning.
What is the pharmacological treatment of asthma?
There is a stepwise pattern:
- Mild asthma= short acting beta-2 agonist, e.g. salbutamol
- Regular anti-inflammatory therapy by inhaled glucocorticoids
- dose increase, long-acting beta-2 agonist
- Prednisolone therapy daily (steriods)
What is the treatment of an acute asthma attack?
High concentration oxygen
High doses of bronchodilators and systemic glucocortoids
What are the symptoms of an acute asthma attack?
Blood gases will show hypoxia
Peak expiratory flow is 33-50% of predicted
What is the peak expiratory flow?
PEF is the highest peak flow number a patient can achieve over a 2-3 week period when their asthma is under control.
What dose a hoarse cough with stridor indictate?
Partial obstruction of a major airway and it requires urgent treatment
What drug can cause patients to develop a cough?
Antiotensin-converting enzyme (ACE) inhibitors
What are the risk factors for COPD?
Tobacco smoke, coal dust exposure, age,
What is COPD?
Defined as a preventable and treatable disease characterised by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases.
What is the pathophysiology of COPD?
It has both pulmonary and systemic components. The presence of airflow limitation combined with premature airway closure leads to gas trapping and hyperinflation, adversely affecting pulmonary and chest wall compliance.
What are the clinical features of COPD?
- breathlessness
- cough and associate sputum production
breath sounds are quiet
What investigations should be done in patients with COPD?
Spirometery used- FEV1/FVC < 70%
Chest x-ray must be used to rule out alternate diagnoses
What is the treatment of COPD?
Bronchodilator therapy needed. Long acting beta agonist and inhaled glucocortoid are given.
Exercise should be encouraged
Oral glucocorticoids can be used in exerbations
How is COPD severity measured?
The following CAN be used:
What is the process of carbohydrate digestion?
Carbohydrate digestion begins in the mouth with the mechanical action of chewing and the chemical action of salivary amylase. Carbohydrates are chemically broken down in the small intestine.
Carbs are broken down into glucose, maltose and lactose.
What is glucose used for in the body?
Through the below pathway, it creates energy for the body.
What is the structure of insulin?
It is a protein composed of two chains, an alpha and beta chain which are linked by sulfur atoms.
What factors regulate insulin secretion?
Blood glucose levels
Free fatty acids and amino acids
Hormones such as leptin and melatonin
When is glucose converted to fats?
When the glucose intake exceeds the body’s energy needs.
Acetyl CoA begins the process of fatty acid synthesis to triglycerides that are stored in the fat tissues of your body.
Regulated by insulin.
What is glucagon?
Glucagon is a hormone produced by alpha cells in the pancreas.
It’s role is to prevent blood sugar levels dropping
It does this by stimulating the conversion of stored glycogen (stored in the liver) to glucose and It promotes the production of glucose from amino acid molecules.
What does the blood pressure reading mean?
Systemic arterial blood pressure
Systolic / diastolic
Why is there two values for blood pressure?
Blood pressure varies throughout the cycle.
Systolic is when the heart contracts and diastolic is when it is relaxed
What is the water tower analogy related to blood pressure?
How can blood flow be calculated?
Q = P / R
Where Q= flow, P= change in pressure gradient and R= resistance
How is blood pressure controlled?
There are baroreceptors that sense short term ABP control. These send signals to brains and the autonomic nervous system sends them back.
The kidneys and the renin-angiotensin/ aldosterone system are longer term.
What is the difference between primary and secondary hypertension?
Secondary is the result of an underlying medical condition
Primary the cause is not known- 90% of cases
What can cause a high blood pressure?
- Exercising
- Failure of kidneys to excrete salt and water (kidney failure, use of NSAIDs)
- Sympathetic nervous system activated (high salt diet, stress, cocaine)
- RAAS system activated
- Confused sensors e.g. renal artery stenosis
What is hypertension?
A blood pressure that is high enough to cause disease
140/90 in most guidelines.
What are the long term consequences of hypertension?
- Stroke
- MI
- heart failure
- kidney failure
- retinopathy
What are the risk factors for hypertension?
BIO= genes for drug metabolism and salt excretion, existing co-morbidities, race
PSYCHO= stress, depression
SOCIAL= smoking, diet, economic status, education, engagement with healthcare
What lifestyle changes can made to intervene for hypertension?
Exercise
Lower potassium and salt intake
Fresh fruit consumption
Weight loss
What are the drugs used in anti-hypertensive therapies?
VASODILATORS= Calcium channel blockers, ACEi, alpha adrenergic receptor blocker
DIRURETICS= thiazides
What is the drug pathway that should be given to black African, type II diabetic or over 55 hypertensive patients?
What are common side effects of calcium channel blockers?
Ankle oedema
What is spironolactone?
Spironolactone is in a class of medications called aldosterone receptor antagonists. It causes the kidneys to eliminate unneeded water and sodium from the body into the urine but reduces the loss of potassium from the body.
Used to treat hypertension but also can cause hyperkalaemia
What are thiazides?
Thiazide diruretics are a class of drugs that inhibit the reabsorption of of luminal sodium in the distal convoluted tubule of the nephron (kidney)
Side effects inlcude hypoatraemia, hypokalaemia and hyperunaemia (can lead to gout).
What is a common side effect of all anti-hypertensive drugs?
Dizziness, which can lead to falls
Why is ambulatory and home measured blood pressure important to monitor?
Due to white coat hypertension, in a clinical practise may be higher.
Ambulatory can provide the ability to detect masked or white-coat hypertension, determine nocturnal blood pressure patterns, and evaluate the impact of antihypertensive treatment.
What are the 3 grades of hypertension?
What are the baroreceptors that are involved in blood pressure control?
These are found in the large veins and in the walls of the atria of the heart. They detect the level of stretch on the heart.
What is endocrine hypertension?
Endocrine causes such as primary aldosteronism, which is excessive aldosterone production by the adrenal glands leads to fluid retention. This leads to hypertension
What is renal hypertension?
Hypertension caused by the narrowing of kidney arteries, causing kidneys to not recieve enough blood and they release renin, which causes an increased blood pressure.
How can hypertension cause damage to the heart?
Excessive pressure can harden arteries, decreasing the flow of blood and oxygen to the heart. This can cause heart failure or a heart attack when the heart muscle is not being adequately perfused.
How does hypertension lead to an increased risk of stroke?
Hypertension causes damage to the arteries, including an increased rate of athlerscleorisis , which causesan increased risk of clots. If this clot blocks blood flow to brain, this can cause a stroke.
What damage to the kidneys can hypertension cause?
High blood pressure can damage the blood vessels in and leading to the kidneys.
Kidney scarring (glomerulosclerosis) occurs when tiny blood vessels within the kidney become scarred and unable to effectively filter fluid and waste from the blood. Glomerulosclerosis can lead to kidney failure.
What damage can hypertension cause to the eyes?
High blood pressure can damage the tiny, delicate blood vessels that supply blood to the eyes, causing damage to the blood vessels in the retina (retinopathy)
This can lead to bleeding in the eye, blurred vision and complete loss of vision.
What vascular damage can hypertension cause?
igh blood pressure can damage the cells of the arteries’ inner lining. When fats from the diet enter the bloodstream, they can collect in the damaged arteries. Eventually, the artery walls become less elastic, limiting blood flow throughout the body.
What are the natural defences against respiratory infections?
- mucus production/ mucus-ciliary escalator
- immune system
- cough reflex
- nose hair
- stomach acid
- conchae
- sneezing
How do chest infections present clinically?
- fever
- Cough
- sputum production, can be green/brown/red/yellow
- breathlessness
- chest pain, often pleuritic
- confusion
What investigations should be done on a patient who has the symptoms of a chest infection?
- PCR test
- chest x-ray
- full blood count
- C reactive protein tests
- sputum
- Arterial blood gases
- blood cultures
What is measured in a full blood count?
provides important information about the kinds and numbers of cells in the blood: red blood cells, white blood cells and platelets
What is measured in arterial blood gas test?
Measures partial pressure of oxygen and carbon dioxide
Also pH and bicarbonate levels
What is the C-reactive protein test?
The level of C-reactive protein (CRP) increases when there’s inflammation in your body. A simple blood test can be done to check your C-reactive protein level.
What is the CURB65 scoring system?
Used to assign risk levels to patients with suspected community-acquired pneumonia
What is the treatment for COVID-19?
Oxygen- aim for saturation > 94%
Glucocorticoids
Anti-virals e.g. remdesivir
However treatment pathway information changes regularly.
What is the treatment for a patient diagnosed with pneumonia?
Oxygen via a face mask if needed
Use the local microbiological guide to decide what antibiotics to use.
What is PCP (Pneumocystis Jirovectii)?
A fungus that causes pneumocystis pneumonia.
Most people who get PCP have a compromised immune system.
Some healthy adults can carry the Pneumocystis fungus in their lungs without having symptoms, and it can spread to other people through air
What is the common anti-microbial treatment of pneumocystis pneumonia?
High dose intravenous cotrimoaxaole and corticosteroids
What are the common microbial causes of pneumonia?
What is the difference between hospital-acquired pneumonia and community pneumonia?
Hospital= Refers to a new episode of pneumonia occurring at least 2 days after admission to hospital.
Community= picked up in the community, usually by droplet infection
What factors that increase risk of respiratory tract infections?
Smoking
Alcohol
Old age
pre-existing lung disease
HIV
indoor air pollution
glucocorticoid therapy
What is the treatment of pneuomina?
In most patients, a 5 day course is adequate.
Axicillin is used for mild severity and other anti-microbials can be given such as clarithromycin and benzylpenicillin if is more severe.
What are some complications of pneumonia?
Deep vein thrombosis
Pleural effusion- build-up of excess fluid between the layers of the pleura outside the lungs.
Retention of sputum causing lobar collapse
Empyema- a collection of pus in the pleural space.
What are common clinical features of an upper respiratory tract infection?
Coughing, runny nose, sneezing and throat pain. You may also get a fever.
What are the clinical features of Tuberculosis?
A cough that lasts more than three weeks
Loss of appetite and unintentional weight loss
Fever
Chills
Night sweats
What is tuberculosis?
It is caused by infection of Myobacterium tuberculosis.
There are 3 stages of TB disease- exposure, latent TB and disease.
he person could have a positive or negative skin or blood test for TB and a positive chest X-ray or biopsy.
How is TB treated?
For latent TB. Often a 3- to 9-month course of 1 or 2 antibiotics will be given to kill off the TB organisms in the body
For active TB. Your healthcare provider may prescribe 2 to 4 or more antibiotics in combination for 6 to 9 months or longer
What are the risk factors for rheumatoid arthritis?
Family history (genetics)
Lower socioeconomic status
Smoking
Chronic inflammation
Silica exposure
Stress
What is Rheumatoid arthritis?
An autoimmune disease
There is a loss of immune tolerance in people who are susceptible, and the immune system starts to attack and damage host cells
What triggers rheumatoid arthritis?
Most of the time the trigger is uknown, however can be due to joint trauma or microenvironement changes
What is citrullination?
The conversion of the amino acid arginine in a protein into the amino acid citrulline. Citrulline is not one of the 20 standard amino acids encoded by DNA in the genetic code. Instead, it is the result of a post-translational modification.
What is the first step in rheumatoid arthritis?
Post-translational modifications of proteins result in citrullinated proteins with a changed structure
The immune system will recognise these as non-sense
Normally the immune system will develop peripheral tolerance, but this breaks down in RA
These are presented to T cells and B cells which create antibodies for the proteins
How do T cells come into contact with citrullinated proteins in RA?
An antigen presenting cell presents an antigen’s peptides to a T cell on a MHC molecule
What is peripheral tolerance?
Activation of T and B cells requires recognition of danger. recognition of antigen in the absence of danger causes lymphocytes to become anergic (inactive) or die
What happens in stage two of rheumatoid arthritis?
- The barrier to synovial fluid is compromised
- inflammatory cells enter the synovial membrane
- Pro-inflammatory CD4 positive short-lived effector T cells eneter and undergo pyroptosis- cell death that triggers inflammation and further immune response
What is stage three of rheumatoid arthritis?
Synovial fibroblasts are activated and macrophages infiltrate.
Pro-inflammatory cytokines produced such as IL-1, TNF and IL-6
T cells also produce RANKL= stimulates osteoclasts= cartilage damage and bone erosions
There is also increased blood flow to the area to bring in more inflammatory cells
What is the typical presentation of rheumatoid arthritis?-
- Bi lateral joint pain
- Aged 50-55 and more likely to be female
Deformity of hands
Morning stiffness
Swelling
Mainly effects smaller joints
Fatigue, tiredness and difficulty concentrating
What functional problems do patient’s complain of with RA?
- Pain
- morning stiffness
- lack of fine motor skills
- loss of grip strength
- hand to do day-to-day tasks, e.g. showering, getting out of bed
- have to take time off work
- difficulty concentrating
How are patients diagnosed with RA?
The diagnosis is clinical
Lab investigations can help confirm:
Anti-cyclic citrullinated peptide antibodies can be detected in blood
Raised c-reactive protein can detect general infection
What do x-rays look like in RA?
Can be initally normal but erosions occur with advanced disease
Joint deformity and joint space narrowing occur too
What is the treatment for RA?
Initially pain relief- NSAIDs and analgesics
Start immunosuppressive treatment early
Prednisolone (a corticosteroid)- short course
Methotrexate
What are the complications of RA?
What is key about the treatment pathways of RA?
Early and aggressive treatment key
What are adjacent drugs that can be given on top of key treatnment for RA?
Biological agent
disease-modifying anti-rheumatic drug
What are examples of when blood clotting can cause disease?
What occurs after a cut in the blood stream?
Vasoconstriction, then platelets adhere to site of injury and a plug formation occurs. There is an activation of the coaglugation cascade leading to formation of fibrin
What prevents blood clotting?
- A healthy endothelium
- anti-thrombosis drugs
- protein C and S inactive clotting factors
- Fibrinolysis
What calculator is used to calculate the probablility of deep vein thrombosis?
Well’s calculator
How does the scoring system on Well’s calculator work?
0 or less = low risk
1-2= moderate risk
3+ = high risk
What is the pathway to confirm diagnosis if the Well’s calculator comes back positive?
D-dimer test or a proximal leg vein ultrasound.
What is wrong with a D-Dimer test in diagnosing deep vein thrombosis?
D-Dimer is a screening test, it is not diagnostic
Many conditions can cause a positive D-Dimer test
What is treatment for deep vein thrombosis?
Most patients treated with factor Xa inhibitors, e.g. apixaban
Low molecular weight heparin e.g. dalteparin followed by a factor Xa inhibitor or warfarin
What are the issues with using warfarin to treat deep vein thrombosis?
It requires alot of monitoring as it has a narrow therapeutic range
What is the triad that can cause thrombosis?
Virchow’s triad
Why is deep vein thrombosis so common in the legs?
Gravity- blood drops down into the legs after not moving for a while
Why do the presence of cancers predispose to deep vein thrombosis?
Tumours release tissue factor molecules- cause hypercoagulability
Tumours produce molecules that damage endothelium- vessel wall injury
What calculator is used to calculate the probability of pulmonary embolism?
Well’s calculator
What investiagtions should be done for low, moderate and high probability pulmonary embolisms?
D-Dimer then subsequent CT if needed for low cases
CT pulmonary angiogram for moderate/high cases
What is the presentation of pulmonary embolism?
- Breathlessness
- Pleuritic chest pain
- Cough
- Calf or leg swelling
- Haemoptysis (less common)
- Syncope (less common)
- Crackles or reduced breath sounds
- Elevated jugular venous pressure
What is the treatment for pulmonary embolism?
Oral factor Xa inhibitor such as apixaban rivaroxaban- option for majority
Low molecular weight heparin e.g. dalteparin followed by warfarin or thrombin inhibitor
What is warfarin?
Vitamin K antagonist
How long does treatment for pulmonary embolism and depp vein thrombosis last?
3 months
Why is venothromboembolism risk increased in hospital patients?
Lass mobile, stasis, likely to be injured in the first place or having surgery
age, cancer, inflammation
What measures reduce the risk of venothromboembolism?
- get them moving
- profilactant coagulant (prevents a clot)
- compression socks and trousers
- adequate hydration
What are the risk factors for deep vein thrombosis?
- Recent surgery or trauma
- Obesity
- Use of oral contraceptives
- Prenancy
- Age > 65 years
- Heart failure
- Previous DVT
What might you find on examination of a patient with deep vein thrombosis?
- Dilated superficial veins
- Unilateral oedema
- Warmth, swelling, tenderness
- Difference in calf diameter
What is a D-Dimer test?
D-Dimer is a degredation product of cross-linked fibrin.
What is a pulmonary embolism?
It is an obstruction of a pulmonary artery or a branch by material such a thrombi, or fat.
What are the symptoms of pulmonary embolism?
Dyspnoea, followed by chest pain and cough
Where are pulmonary emboli thought to arise from?
Lower extremity proximal veins such as iliac, femoral and popliteal
What are some cardiovascular causes of chest pain?
Ischaemic heart disease
Pericarditis
Aortic dissection
What are respiratory causes of chest pain?
Pneumothorax, pneumonia, pulmonary embolus, pleurisy and asthma
Usually accompanied by cough and breathlessness
What are some of the causes of chest pain due to the muscoskeletal system?
- Muscle strain
- Rib fracture
- Constochondritis (inflammation in the costochondral joint) and myositis
Usually worse with movement
What are some gastrointestinal causes of chest pain?
Oesophageal reflux
Peptic ulcers
Pancreatitis
Gallstones
Hiatus Hernia
Usually related to eating and symptoms of heartburn
What are some neural causes of chest pain?
Shingles, nerve entrapment, anxiety and neuropathic pain
Usually follows a dermatomal pattern, might be related psychiatric symptoms
When does ischemic heart disease start to happen, and to who?
Starts to happen in early 20s, more likely men and smokers
What is the simple summary of how heart disease occurs?
What are the 3 layers of arteries normally?
The normal artery contains three layers.
- Inner layer, tunica intima is lined by a monolayer od endothelial cells that is in contact with blood
- Middle layer, tunica media contain smooth muscle cells within a ECM
- Outer layer, adventitia contains mast cells, nerve endings and microvessels
What is the first step shown below in atherosclerosis?
First steps include adhesion of blood leukocytes to the activated endothelial monolayer, directed migration of the bound leukocytes into the intima, maturation of monocytes (the most numerous of the leukocytes recruited) into macrophages, and their uptake of lipid, yielding foam cells.
What is the second step below in athlerosclerosis?
Smooth muscle cells migrate from the media to the intima
There is heightened synthesis of ECM macromolecules such as collagen, elastin and proteoglycans
Macrophages and smooth muscle cells die
Extracellular lipid dervived from dead cells can accumulate in the central region of a plaque, often denoted the lipid or necrotic core
What is the third step in atherosclerosis shown below?
If a plaques fibrous cap ruptures which enables blood coagulation components to come into contact with tissue factors in the plaque’s interior, triggering the thrombus that extends into the vessel lumen, where it can impede blood flow.
How do the different atherosclerosis stages link to clinical problems?
Stage 1= angina
Stage 2= unstable angina
Stage 3= plaque rupture can lead to acute myocardial infraction
What is angina and what are the symptoms?
A mismatch between cardiac oxygen supply and delivery.
Exertional chest pain, relieved by rest
There is pain/tightness/discomfort in central chest but can radiate to throat/arm/back
Often worse in cold and windy weather
How are angina symptoms relieved?
Sublingual glyceryl trinitrate (GTN) spray
What examinations should be done on a patient presenting with chest pain?
What is included in management of angina?
Lifetsyle= stop smoking, weight loss, exercise, diet
Drugs= GTN spray, beta-blockers, aspirin, calcium channel antagonists
What type of chest pain is caused by acute coronary syndrome?
Chest pain- tightness, pressure, crushing with gardual onset
Wrose with exertion
Radiates to neck, jaw and arms
Usually lasts no more than 20 minutes
Accompanied by nausea, vomiting, sweating and breathlessness
What are the risk factors for acute coronary syndrome?
Smoking
Diabetes
Hypertension
Hypercholsterolaemia
History of ischemic heart disease
What are investiagtions to do in patients with suspected acute coronary syndrome?
12 lead ECG
Serum highly sensitive troponin
What changes in an ECG during a acute coronary attack?
There is ST elevation in 2 contiguous leads
How does an ECG change over time after a heart attack?
hours after, a deeper Q wave arises- which never goes away after an MI
What is ST depression in a ECG a sign of?
Ongoing ischemic heart disease, where the artery is not fully blocked
What are secondary prevention drugs of a heart attack?
- Aspirin
- Beta blockers
- ACE inhibitors
- Treat diabetes
- Life style interventions
What is Pericarditis and what causes it?
The inflammation of the lining of the heart due to viral infection, autoimmune disease, post-MI or cancer
Uusally worse on inspiration and leaning forward can make it better
What is aortic dissection, what are the symptoms and what are it’s effects?
Aoric dissection is when a tear occurs in the aorta
Is acute severe chest pain- knife like, tearing and radiates to back
Can occlude (obstruct) arterial branches including the coronary arteries, can also ruptures into pericardial sac.
What are cardiac causes of breathlessness?
Myocardial infarction
Angina
Pericarditis
Aortic dissection
What are causes of palpitations?
Tachyarrhythmias
Ectopic beats (extra heartbeats)
Anxiety
Hyperthyroidism
Drugs
What are causes of syncope or presyncope?
Arrhythmias
Postural hypertension
Aortic stenosis (narrowing of aortic valve opening)
Simple faints
Epilepsy
Anxiety
What is important to obtain in a patient’s history with chest pain?
Onset of pain (abrupt, gradual)
Provocation (which activites provoke/alliviate pain)
Quality of pain (squeezing or sharp)
Radiation
Site of pain
Timing (constant or episodic)
What investigations should be done in a patient with suspected aortic dissection?
ECG- to rule out myocardial infarction
Echocardiology
Chest x-ray and CT
What is the chest pain felt like in myocardial ischemia, stable angina and unstable angina?
Myocardial ischemia= dull, tight or pressing feeling. Felt diffusely across chest and may radiate to arms, throat or jaw
Stable angina= caused by chronic narrowing in one or more arteries, pain is felt in exertion, in the cold/windy weather. Pain is prompted by rest.
Unstable angina= caused by a sudden severe narrowing in a coronary artery, usually abrupt onset or worsening of chest pain, occur on minimal exertion
What is the difference between myocardial ischaemia and myocardial infarction?
Myocardial ischemia occurs when blood flow to your heart is reduced, preventing the heart muscle from receiving enough oxygen
A heart attack (myocardial infarction or MI) is a serious medical emergency in which the supply of blood to the heart is suddenly blocked
What is pleurisy?
a condition in which the pleura — two large, thin layers of tissue that separate your lungs from your chest wall — becomes inflamed. Also called pleuritis, pleurisy causes sharp chest pain (pleuritic pain) that worsens during breathing.
What are risk factors for ischaemic heart disease?
Men over 45 years and women over 55.
Smoking
High Blood Pressure.
Hypercholesterolemia.
Diabetes.
Genetics.
Sedentary lifestyle.
Obesity.
What is the inital managment of myocardial infract?
- Give them angiogram to see where the blockage is
- Remove the blockage surgery- stent
- If cannot do this- give them anticoagulants e.g. eminase, or tPA
What are different thrombilytic drugs and what do they do?
Break up fibrin clots
The most commonly used clot-busting drugs – also known as thrombolytic agents – include: Eminase (anistreplase) Retavase (reteplase) Streptase (streptokinase, kabikinase) t-PA
What is syncope and presyncope?
Syncope is loss of consciousness due to reduced cerebral perfusion, presyncope usually refers to light-headedness when some feels they may be about to lose consciousness.
What is key when taking a history of a patient experiancing syncope?
- Ensure you understand what the patient means
- Detailed description of timing, what patient was doing, what they experienced, how long they were unconscious for and how they felt afterwards
- Obtain a witness account if possible
- Past medical history, eg are they diabetic and are having a hypo?
- Split history into 3 parts; before the syncope, during the syncope (witness account important here) and after.
What are the common causes of syncope?
- cardiovascular causes such as arrhythmias or structural heart disease
- Postural or orthostatic (elderly) hypotension
- epilepsy
- Vasovagal syncope
- Drug intoxications
- hypoglycaemia
What is the route that electrical impulses take around the heart?
What is sinus tachycardia, bradycaardia and arrhythmia?
How do you measure HR on a ECG?
Count the number of sqaures between the R waves
Divide 300 by this number
What is the difference between arrhythmias and palpitations?
Arrthythmias are a contant abnormal heart beat
A palpitation can be a one off event (does not have to be however)
What drinks can cause palpitations?
Energy drinks
Coffee- caffine
Alcohol
What is this an ECG of?
QRS complex are normal duration
Fast heart beat
= supraventricular tachycardia
What is supraventricular tachycardia?
Supra=above
There is a problem above the ventricles (e.g. SA node, atria or AV node) that is causing the ventricles to beat faster than 90
QRS complexes are normal
What is atrial fibrillation?
What influences the SA node?
Sympathic nervous system from sympathetic chain- speeds up HR
Parasympathetic nervous system from vagus nerve- slows down HR
Adrenaline- catecholamines faster
Acetylcholine (muscarinic) slows
What does the ECG for atrial fibrillation look like?
No P waves
QRS normal
Highly irregular- differences in distance between QRS
What innervates vagus nerve and slows down conduction rate and what does this treat?
Carotid sinus massage
Valvsalva manoeuvre
Cold water on face
=SUPRAVENTRICULAR TACHYCARDIA
What drug blocks the AV node?
Intravenous adenosine
What are alternate causes for lightheadedness other than syncope?
Hypoglycaemia- diabetes
Vertigo
Hyperventilation (could be caused by anxiety)
What is the peak age of diagnosis of cancer?
85-89 years
What are the most common cancers in men and women?
Prostate and breast
Trachea, bronchus and lung
Colorectal
What are the lifestyle changes that can reduce the risk of cancer?
- Stop smoking
- Protect skin from sun damage
- Reduce alcohol intake
- Reduce meat consumption, eat healthy and eat fibre
- Don’t re-use single use plastics
- Avoid environmental pollution/ abestos
- Get the HPV vaccine
- Breastfeed if possible and earlier pregnancy
If a patient comes in with suspected lung cancer, what investigations should be done?
Chest x-ray, full blood count, CT and sputum testing
If a patient comes in with suspected colorectal cancer (due to lower abdominal pain and weight loss)?
Full blood count, urea and electrolytes, liver function tests and colonscopy
For what cancers mean having a lower socioeconomic status mean there is less chance of survival?
All cancers, except for malignant melanoma
What cancers have the highest probability of survival?
The highest five-year survival estimates are seen in patients with testicular cancer (97%), melanoma of skin (92.3%) and prostate cancer (88%).
What cancers have the lowest probability of survival?
The cancers with the lowest five-year survival estimates are mesothelioma (7.2%), pancreatic cancer (7.3%) and brain cancer (12.8%).
What are signs and symptoms indicative of cancer?
- Fatigue or extreme tiredness
- Weight loss or gain
- Eating problems such as not feeling hungry, trouble swallowing, belly pain, or nausea and vomiting
- Swelling or lumps anywhere in the body
- Thickening or lump in the breast or other part of the body
- Pain, especially new or with no known reason
- Skin changes
- Cough or hoarseness that does not go away
- Unusual bleeding or bruising for no known reason
What is the presentation of lung cancer?
Most common presenting symptoms are cough, chest pain, haemoptysis, dyspnoea, and weight loss.
What are the symptoms of colorectal cancer?
- rectal cancer
- change in bowel habits
- abdominal pain
- weight loss
- anorexia
What are red flag symptoms and signs for back pain?
- Weakness/numbness in both legs
- Saddle anaesthesia
- Urine retention or incontinence, faecal incontinence
- Nocturnal pain
- Weight loss
- Fevers
- Thoracic pain
- Recent trauma
What are signs and symptoms of cauda equina and spinal cord compression?
- Weakness/numbness in both legs
- Saddle anaesthesia
- Urine retention or incontinence, faecal incontinence
What investiagtions should be done in a patient with spinal cord compression?
Full blood count, urea and electrolytes, calcium, prostate specific antigen
MR scan spine
What is a spinal cord compression?
Spinal cord compression is caused by any condition that puts pressure on your spinal cord.
Malignant SCC can happen when cancer grows in the bones of the spine or in the tissues around the spinal cord.
What is cauda equina syndrome?
Cauda equina syndrome is a rare and severe type of spinal stenosis where all of the nerves in the lower back suddenly become severely compressed.
The doctors will usually give you high doses of a steroid (dexamethasone) to reduce pressure and swelling around the spinal cord and reduce the pain.
Then radiotherapy, chemotherapy or surgery are used.
How can you tell the difference between epileptic seizures and syncope?
Epileptic seizure is spontaneous
Often syncope is preceded by a prodrome or period of presyncope
One of the most important clues usually comes from an observant bystander who witnesses the event and is able to report if the person went limp then convulsed (syncope) or if the episode began with convulsions- shaking (seizure).
What are the initial investigations for a patient presenting with syncope?
Clinical history and physical examination key
12 lead ECG
The pulse rate and rhythm and the BP- supine and standing
What are common symptoms of patients with cardiac arrhythmias?
Palpitations
Loss of consiousness- syncope
Breathlessness
Fluttering in chest/high/low heart beat
Lightheadedness or dizziness
What is the treatment for atrial fibrillation?
- Drugs to control HR- atenolol and propanolol (beta blockers)
- Calcium channel blockers
- Sodium and potassium channel blockers
- Anticoagulants such as apixaban and Heparin to stop risk of stroke
What are complications of artrial fibrillation?
People with atrial fibrillation are at increased risk of having a stroke. In extreme cases, atrial fibrillation can also lead to heart failure.
When the upper chambers of the heart (atria) do not pump efficiently, as in atrial fibrillation, there’s a risk of blood clots forming
If your atrial fibrillation is persistent, it may start to weaken your heart.- in extreme cases can lead to heart failure
What are side effects and complications of anti-coagulants
Excessive bleeding- for example in urine or nosebleeds
Possible other side effects include: diarrhoea or constipation, feeling and being sick, indigestion, dizziness and headaches
What part of the heart does sinus, supraventricular and ventricular tachycardia occur?
Sinus= sinus depolarising too fast, e.g. fight or flight
Supraventricular tachycardia= problem in atrial muscle or AV node
Ventricular tachycardia= problem in bundle of his, connecting branches of muscle
What are the P wave, QRS wave and T wave associated with?
P= atrial depolarisation
In between= AV node conduction
QRS= ventricular depolarisation
T wave= repolarisation of wave
QRS hides atrial repolarisation
What does the ECG of ventricular tachycardia look like?
What is the problem with developing complete heart block?
The ventricle has too slow a pace and CO decreases- causes lack of perfusion and can cause fainting
What is the treatment for ventricular tachycardia?
Defibulator (DC cardioversion)
What are the different types of heart block?
First degree= slow conduction through AV node
Second degree= - Mobitiz 1= P wave and QRS get out of sync until a QRS is missed
Mobitz 2= miss a QRS randomly
2:1= every 2 p waves there is one QRS
What does the ECG look for first degree heart block?
What does the ECG look like for Second degree (Mobitz I, Mobitz II and 2:1 block)?
What does the ECG look like for Complete heart block/ 3rd degree heart block?
What is the emergency treatment for complete heart block?
