The Patient - Semester 2 Flashcards
1
Q
What are the conducting airways and what are the components?
A
Anatomic dead space
Nose, mouth, pharynx, larynx, trachea, bronchi, bronchioles, terminal bronichioles
2
Q
What adaptation prevents the trachea and bronchi from collapsing?
A
Cartilage in the walls
3
Q
What are the respiratory airways and what are the components?
A
Sites of gas exchange
Respiratory bronchioles, alveolar ducts, alveoli
4
Q
What does one respiratory cycle consist of?
A
One inspiration and one expiration
5
Q
Define ventilation
A
Bulk air entry caused by a drop in pressure as a result of increased lung volume
6
Q
What are the pleural sacs and what are they connected to?
A
Fluid filled sacs surrounding the lungs
Inner membrane is connected to the lung and outer membrane is connected to the thoracic wall (spinal column, ribs and intercostal muscles) and diaphragm by connective tissue
7
Q
How do the lungs expand?
A
Contraction of the diaphragm and intercostal muscles pulls on the pleural sacs which subsequently pulls on the elastic lung tissue, causing them to expand
8
Q
What are the functions of the conducting airways?
A
- Low resistance airflow pathway
- Speech (larynx)
- Efficient O2/CO2 exchange - Warms and moistens air entering
- Infection defence by macrophages
- Mucus secretion - immune defence
9
Q
How does mucus provide a barrier to infection in the conducting airways?
A
Mucus traps dust and microorganisms, cilia then wafts mucus towards pharynx where it can be swallowed to kill bacteria
10
Q
How is movement of the mucus maintained?
A
Cl- moves out of epithelial cells through CFTR channel in apical membrane, watery fluid follows by osmosis
11
Q
What is cystic fibrosis?
A
Defective CFTR results in inefficient Cl- movement and therefore a build up of mucus, increasing chances of infection as pathogens are not removed
12
Q
What is a pneumothorax?
A
Breakage of pleural sac as a result of disease or injury - this results in air entering the chest cavity
The external air pressure causes the chest wall to expand and the lungs to collapse
13
Q
How is injury to the lung contained to one side?
A
Lungs are isolated in pleural cavities so damage to one side prevents both lungs collapsing
14
Q
What diseases can cause a pneumothorax?
A
Pneumonia and emphysema
15
Q
What are the treatments for a minor, moderate and severe pneumothorax?
A
- Minor: Monitor by x ray and let body absorb air
- Moderate: Remove external air using a needle and tube
- Severe: Surgically repair lung or remove if damage is too severe
16
Q
Define tidal volume, residual volume and vital capacity
A
- Tidal volume is the amount of air inhaled and exhaled during normal breathing
- Residual volume is the amount of air left in the lungs even after a forced exhalation
- Vital capacity = total volume - residual volume, can be worked out by measuring air expelled after taking a deep breath and and then a forced exhalation
17
Q
What is the volume of an approximate inhalation/exhalation?
A
~500ml
18
Q
What are the two ways of measuring ventilation and why are they important?
A
- Minute ventilation: Tidal vol. x Resp. Rate (ml/min)
- Alveolar Ventilation: (Tidal vol. - Dead Space) x Resp. Rate (ml/min)
Differences can highlight respiratory issues (e.g. shallow breathing which would result in inefficient gas exchange)
19
Q
What is the volume of anatomical dead space?
A
~150ml
20
Q
What are the lung function tests and what measurements are taken?
A
Spirometry, peak flow meter
FVC: Forced vital capacity
FEV1: Forced expiratory volume (in 1 sec) - Usually about 80% of FVC
21
Q
What observations are made in Obstructive Lung Disease?
Give examples of conditions
A
- Normal FVC but FEV1 less than 80% due to resistance in airways
Asthma, COPD, CF
22
Q
What observations are made in Restrictive Lung Disease?
Give examples of conditions
A
- Reduced FVC and FEV1 but FEV1 still ~80% due to poor expansion of the lungs
Fibrosing alveolitis, malignant infiltrations (e.g. tumours)
23
Q
What is lung compliance?
How is it worked out?
A
Ease of expansion of the lungs - depends on relationship between transpulmonary pressure (difference in pleural and alveolar pressure) and lung volume
Cl = Change in vol/Change in pressure
24
Q
Describe what would be seen in normal, low and high compliance
List conditions that may alter compliance
A
Normal: Increase in TP causes increase in lung volume
High: Small increase in TP causes large increase in lung volume (emphysema)
Low: Large increase in TP causes small increase in lung volume (fibrosis, pneumonia, oedema)
25
What are the two types of cells in the lungs?
Type 1: Gaseous exchange cells
| Type 2: Cuboid cells, surfactant producers
26
What is the purpose of surfactant in the lungs?
Reduces lung surface tension to prevent alveoli collapsing
27
What is Newborn Respiratory Distress Syndrome?
Underdeveloped type 2 cells result in less surfactant production so lungs cannot stay open
28
What other conditions (generic) can cause low lung compliance?
Disorders affecting rib/spinal column articulation as the pleural sacs are connected to these
29
Why do ventilation and perfusion need to be matched?
Inequality results in reduced O2 entry to body
30
What is emphysema?
What causes it and how is it treated?
Degeneration of alveolar/bronchiole walls by proteases (produced by leukocytes), surrounding capillaries may also be affected
Usually caused by smoking and insufficient oxygen intake results in patient being put on O2
31
What is asthma? What causes it?
Inflammation of the conducting airways due to excess mucus and contraction of smooth muscle
Caused by environmental allergens
32
How are bronchodilators used to treat asthma?
- Beta receptors agonists: Mimic action of adrenaline by activating adenylate cyclase so ATP is converted to cAMP, cAMP caused relaxation of smooth muscle
- Phosphodiesterase inhibitors: These inhibit cAMP breakdown, maintaining relaxation of the airway smooth muscle
33
How are corticosteroids used to treat asthma?
- Corticosteroid binds to glucocorticoid receptor in epithelial cell cytoplasm
- Heat shock proteins dissociate from the receptor, allowing the receptor-drug complex to move to the nucleus where is binds to regions of DNA that transcribe for cytokines
- Reduction of cytokines results in reduced inflammation
34
What is the allergic component of asthma?
Overproduction of IgE - IgE binds to Fce region on mast cells, basophils and dendritic cells which causes release of histamine, cytokines, prostaglandins and leukotrienes
35
How are monoclonal antibodies used to treat asthma?
Give an example of one
- MAbs bind to Fc region on IgE to prevent binding to inflammatory cells
- Release of inflammatory markers inhibited
Omalizumab
36
What structures control breathing?
Pons and Medulla in the brainstem
37
What neurones are involved in breathing control and how do they have this effect?
Inspiratory, expiratory and mixed neurones from the pontine respiratory group
Impulses from neurones cause contraction of diaphragm and intercostal muscles
38
Where are central chemoreceptors found and what do they monitor?
- Brain stem medulla
| - pH and pCO2 of cerebrospinal fluid
39
Where are peripheral chemoreceptors found and what do they monitor?
- Carotid and aortic bodies
| - pH, pCO2 and pO2 of arterial blood
40
Why is high CO2 dangerous and how is it controlled?
High CO2 is toxic to respiratory neurones in the medulla
High levels detected by receptors which results in increased contraction of intercostal muscles and diaphragm
41
What causes reversible bronchospasm in asthma?
Release of cytokines by T-lymphocytes
42
What are the symptoms of asthma?
Shortness of breath, cough, dyspnoea, wheeze
43
What are the aims of asthma treatment?
Symptom control, prevent exacerbations and requirement of rescue pack, improve lung function, promote self care, minimise side effects
44
How can asthma be managed without medicines?
```
Avoid trigger
Avoid cold air exposure
Lifestyle changes (weight, smoking)
Avoid use of NSAIDs and beta-blockers
Buteyko breathing technique - slow, gentle breathing through nose to prevent drying airways
```
45
What routes can be used for administration of asthma drugs?
Oral or inhaled
46
What are the types of inhaled formulations?
Inhalers as relievers (SABAs), controllers (LABAs) and preventers (ICS)
Nebulisers in cases where coordination cannot be controlled
47
How are beta-2 agonists used in asthma treatment?
Relaxation of bronchial smooth muscle and enhanced mucus clearance by cilia
48
What are the side effects of b-2 agonists?
Tremor, nervous tension, headache, peripheral vasodilation, tachycardia, hyperkalaemia
49
What are the different types of corticosteroid treatment in asthma?
- Inhaled for prevention (beclometasone)
- 40-50mg orally for 5 days post-acute attack (prednisolone)
- IV in case of inability to take orally (hydrocortisone)
50
When is an ICS used as a preventer in asthma treatment?
- Exacerbation in the last 2 years
- Experiencing symptoms and use of b-agonist more than 3 times weekly
- Experiencing waking frequently
51
What are the side effects of an ICS?
Dysphonia, oral thrush, adrenal suppression, hypertension, osteoporosis, skin thinning, hyperglycaemia, moon face, acne
52
How are leukotriene antagonists used in asthma treatment?
- Given orally
| - Prevention of bronchoconstriction, oedema and mucus production
53
Give two examples of leukotriene antagonists
Montelukast, Zafirlukast
54
What are the side effects of leukotriene antagonists?
Abdominal pain, headache, thirst, rash, sleep disturbance, effects on the CNS
55
How are methylxanthines used in asthma treatment?
Phosphodiesterase inhibitors - maintain bronchodilation (cAMP)
Prevent synthesis of leukotrienes
56
Give two examples of methylxanthines and their RoA
Theophylline - Oral
| Aminophylline - Oral/IV
57
What are the issues with methylxanthines?
Narrow therapeutic index
| CYP450 metabolism - drug interactions
58
What are the side effects of methylxanthines?
Nausea, diarrhoea, nervousness, headache, vomiting, insomnia, arrhythmia, hyperglycaemia, convulsions, death by overdose
59
What factors can reduce clearance of methylxanthines?
Congestive heart failure
Liver disease
Obesity
Enzyme inhibition
60
How are cromones used in asthma treatment? Give an example
Inhibit histamine release from mast cells
| Nedocromil
61
What are the side effects of cromones?
Nausea and vomiting, bitter taste, indigestion (dyspepsia)
62
Give some examples of immunosuppressants used in asthmas treatment
Methotrexate
Ciclosporin
Gold
63
How are MAbs administered and how long is treatment?
Subcutaneously for 2-4 weeks
64
What are the steps for managing chronic asthma in adults?
- SABA prn
- Low dose ICS for prevention
- Add LABA if required
- If still uncontrolled, increase ICS dose
- Stop LABA and increase ICS further
- Trial LTA, SR theophylline or long-acting muscarinic antagonist (LAMA)
- Consider fourth drug
- Specialist referral
65
What factors affect Peak Expiratory Flow? What percentage of expected should it be?
Effort, age, height, sex
At least 80% of expected
66
What characterises acute severe asthma?
PEF <50%, dysphonia, RR >25, HR >110
67
What characterises acute life threatening asthma?
Severe PLUS silent chest, cyanosis, bradycardia, confusion, exhaustion, coma, inability to speak full sentences, PEF <33%
68
What drugs would be given if a patient is hospitalised for acute asthma?
- Nebulised b2-agonist, IV/oral steroid
| - Possibly ipratropium nebuliser, IV MgSO4, IV aminophylline/salbutamol
69
What are the monitoring requirements in acute asthma?
PEF, O2 saturation, ABGs, HR, RR, theophylline level, K+ level, glucose level, hydration, WCC, CRP
70
What should be checked before discharging an asthma patient?
Inhaler technique
71
What is COPD?
```
Parenchymal damage (damage to functional parts of airways)
Progressive airway obstruction
Treatable but not curable
```
72
At what age is COPD a more likely diagnosis than asthma?
Above 35 years
73
What are the symptoms of COPD?
Chronic cough, mucus production, breathlessness
74
How is COPD diagnosed?
Spirometry, chest xray and FBC
75
What are the systematic effects of COPD?
Weight loss, skeletal muscle loss, osteoporosis, depression, increased risk of CVD
76
What increases the risk factor for COPD?
Smoking, age, gender (male) occupational hazards, previous lung impairment
77
Name a genetic risk factor for COPD
Alpha-1 antitrypsin deficiency
78
What are the aims of COPD treatment?
Improve day-to-day symptoms, prevent acute infective exacerbations, slow progression of disease, maintain nutritional intake, improve quality of life, smoking cessation
79
How do antimuscarinics reduce airway constriction?
Acetylcholine stimulates M3 receptors which cause bronchoconstriction, antimuscarinics prevent the action of acetylcholine
80
What are the side effects of antimuscarinics?
Dry mouth, blurred vision, urinary retention, constipation, hypotension
81
When are corticosteroids used in treatment of COPD?
If patient has FEV <50% and SABA has little or no effect
82
What should be avoided if patient is on oxygen therapy?
Smoking due to flammability
83
When is oxygen therapy used in COPD?
if FEV <35%
84
What oxygen concentration is used to prevent respiratory depression and why?
24-28% to prevent hypoxic drive (body responds to low O2 rather than high CO2 - oxygen treatment then takes away requirement to breath as body registers O2 levels as high)
85
How are infectious exacerbations prevented and how are they treated?
Administration of influenza and pneumococcal vaccines
Chest infections are treated with antibiotics
86
What are mucolytics and when are they used in COPD treatment?
Reduce viscosity of mucus so it is easier to expel from the airways
Used when patient has a chronic productive cough
87
How are LAMAs/LABAs used in COPD treatment?
Unmanaged COPD, if FEV <80% give combination inhaler of LABA/ICS
If still unmanaged give LAMA + combination inhaler
88
What lifestyle changes can be made to improve COPD symptoms?
Smoking cessation, exercise, nutrition management
89
How often is COPD reviewed and what parameters and checked?
Annually
FEV, dyspnoea, BMI, depression, inhaler technique and medication review
90
What is the danger of using steroids in COPD treatment?
Steroid increase susceptibility to infection so infective exacerbations (chest infections) are more likely
91
What antibiotics are used to treat a chest infection?
Amoxicillin 500mg TDS, tetracycline, doxycycline 200mg STAT then 100mg OD
May use broad spectrum cephalosporin or macrolide
92
What is cor pulmonale?
Right side heart death due to damage to the pulmonary circuit as a result of hypertension
93
What is polycythaemia?
RBC and haematocrit level rises due to hypoxia, blood viscosity increases
94
What are the functions of the tissues and organs in the GIT?
Specialised for digestion and absorption
95
Define alimentary
Relating to nutrition
96
What are the components of the GIT?
Mouth, pharynx, oesophagus, stomach, small intestine (duodenum, jejunum, ileum), large intestine (colon,), rectum, anus
97
What are the accessory structures to the GIT and what are their functions?
Salivary glands (sublingual, submandibular and parotid)
Secretion of amylase and lipase, mucin production (glycoprotein that provides lubrication for swallowing)
98
What does the Mumps virus affect and what are the symptoms?
Affects parotid glands
| Swelling to side of face and neck
99
Describe the mechanism of swallowing
Food bolus sensed by tactile receptors in the back of the throat, signal sent to medulla oblongata which then sends impulses to throat musculature, causing coordination of swallowing
100
What 6 nerve groups are involved in coordination of swallowing?
Trigeminal, facial, glossopharyngeal, vagus, spinal accessory and hypoglossal
101
What patients may develop dysphagia?
Stroke patients due to nerve damage
102
Describe the journey of a food bolus
Mouth -> Oesophagus -> Stomach (past oesophageal hiatus)
103
What is a hiatus hernia?
Stomach pushes through diaphragm resulting in acid reflux
104
What is Barrett's Oesophagus?
Squamous epithelial cells damaged by acid reflux and then replaced with abnormal columnar cells (pre-cancerous)
Patients at higher risk of developing adenocarcinoma
105
What adaptation prevents stomach acid from entering the oesophagus?
Lower oesophageal sphincter seals stomach
106
What are the four types of gastric cells?
Mucus cells, G-Cells, Chief Cells, Parietal Cells
107
What are the functions of G-Cells?
Gastrin secretion, gastrin binds to parietal cells causing HCl release
108
What are the functions of Chief Cells?
```
Secrete pepsinogen (pepsin in inactive form)
Secrete gastric lipase
```
109
What are the functions of Parietal Cells?
HCl release (p. cell pumps H+ into stomach lumen):
Food receptors send impulses to stomach causing release of acetylcholine
Gastrin binds to parietal cells causing HCl release
Stomach distension causes release of histamine which causes release of HCl
110
How are H2 receptor antagonists used to treat acid reflux? Give two examples
Histamine effects reduced or abolished by blocking receptor
Cimetidine and Ranitidine
111
How are PPIs used to treat acid reflux?
Inhibition of H+/K+ ATPase pump, preventing H+ entering stomach so no formation of HCl
112
Why are enteric coatings used in drug formulations? Give two examples that may need enteric coatings
Some drugs may undergo degradation by HCl in the stomach, enteric coating protects active ingredient
Penicillin G and erythromycin
113
What structures are best absorbed in the BIT and why?
Lipid-soluble, weakly acidic drugs because they remain unionised and can cross the lipid membrane
114
What is the main site of absorption in the GIT?
Small intestine
115
What are the protective adaptations of the stomach?
- Pepsin secreted as inactive pepsinogen to prevent breakdown of stomach proteins
- Mucus layer produced by foveolar cells protects stomach epithelium - neutralises stomach acid and protects from protease digestion
- Epithelial cells connected by tight junctions prevents exposure of epithelium to acid/pepsin
- Cells are replaced every 2-3 days
116
How gastric/duodenal ulcers formed?
Breakdown of protective adaptations leads to damage of the stomach epithelium
If damage extends deep enough it can damage blood vessels and cause a haemorrhage
If damage erodes GIT wall (perforated ulcer) chyme may enter peritoneal cavity
117
What is peritonitis?
Inflammation of the peritoneum due to contact with chyme, can lead to sepsis
118
What is the relationship between Helicobacter pylori and gastric ulcers?
Infections are a common cause of ulcers, eradication of H. pylori dramatically reduced incidence of ulcers
119
What are the treatments and doses of H.pylori infections?
Two antibiotics and PPI:
Clarithromycin (500mg BD) + Amoxicillin (1g BD) + Omeprazole/Esomeprazole (20mg BD)
Clarithromycin (250mg BD) + Metronidazole (400mg BD) + Omeprazole/Esomeprazole (20mg BD)
120
What is peristalsis?
Coordinated contraction of intestine to push a food bolus along the lumen
Circular muscles contract to prevent the backwards movement of a food bolus whereas longitudinal muscles contract to push the food bolus along
121
How is diarrhoea characterised and how is it treated?
Excessive fluid and ion loss due to excessive longitudinal contraction
Loperamide - Targets opioid receptors of myenteric plexus to reduce contraction and increase contact time of food bolus, allows reabsorption of ions and water
122
Where is bile acid produced and stored?
Produced in the liver and stored in the gall bladder
123
What is the purpose of bile acids?
Released into the intestine to allow lipid absorption by emulsification, then reabsorbed in ileum
124
What are the lipid soluble vitamins?
A, D, E and K
125
Why are gastric surgeries used for weight loss and how does it work?
What procedures are there?
Used in severe cases of weight loss
Reduce capacity of stomach so lower food intake = lower calorific intake
Gastric band, gastric sleeve, gastric bypass
126
What other conditions can peptic ulcer treatment be used for and how may they differ?
Dyspepsia, reflux, duodenal/gastric ulcers, NSAID-related ulcers, gastro-oesophageal reflux disease
Dose, administration, treatment duration
127
What is GORD and what are the symptoms?
Reflux with similar symptoms to chronic heartburn
Chronic cough, laryngitis
128
What are the ALARMS symptoms of dyspepsia/heartburn/peptics ulcers?
Anaemia, Loss of weight, Anorexia, Recurrent problems, Melaena/haematemesis (blood in vomit/stools), Swallowing problems
129
How are antacids used for treatment of peptic ulcer disease?
Neutralise stomach acid, when required and at mealtimes
Liquids are more effective
130
List some effects of components of antacids
Mg - Laxative effect
Al - Constipation
Ca - Hypercalcaemia/Rebound acid secretion
131
When are low Na+ formulations used?
Renal/cardiac patients, hypertension patients, pregnant patients
132
When are products containing Na2CO3 contraindicated?
Patients with reduced salt intake
133
How are H2 antagonists used in peptic ulcer disease?
Used at higher doses for peptic ulcer treatment
134
What drugs does cimetidine interact with and what is the effect?
Warfarin, phenytoin, carbamazepine, valproate, theophylline, sildenafil
Inhibits metabolism
135
What are the side effects of H2 antagonist interactions?
Headache, diarrhoea, dizziness, rash, altered LFTs
136
How do Helicobacter pylori bacteria replicate?
Convert urea to CO2 and NH3 using water, NH3 neutralises acid
137
How do Helicobacter pylori cause damage?
Bacterial mucinase - Mucosal damage
Gastric acid, proteases and effector molecules then cause mucosal inflammation
Cytokines and NH3 cause mucosal cell death
138
How is a H. pylori infection detected?
Antibodies in serum, saliva and urine
Urease activity on C-13 urea may produce C-13 CO2
Mucosal biopsies
High antibody titre
139
What are the treatment aims for H. pylori infections?
Eradication
140
How does treatment differ in complicated ulceration?
PPI continued for 3 weeks longer
141
How is GORD treated?
Full dose PPI for 1-2 months, lower dose then eventually stop
142
How is GORD in children treated?
Alter frequency or volume of feed, make feed thicker, use alginate, H2 antagonist or PPI
143
How can NSAIDs cause peptic ulcer disease?
Prevent production of mucous, bicarbonates and prostaglandins which are all protective factors for gastric acid damage
144
How do prostaglandin analogues have a protective effect?
PGE1 has antisecretory and cytoprotective effects
| Misoprostol (antagonist) increases mucus production causing ulcer healing and preventative uses
145
What action should be taken in the case of continuing NSAIDs?
Long term PPI treatment
PPI + misoprostol after healing
PPI + Cox-2 inhibitor
146
Define achlorhydria
Low gastric acid production
147
What adaptations increase the GIT capacity for digestion and absorption?
Highly perfused - surrounding capillaries and lacteals Folded - large SA
Epithelium only one cell thick
Digestive enzymes convert large macromolecules into small, absorbable molecules
148
Give the digestion of three sugars and the enzymes that do them
Lactose -> Glucose + Galactose (Lactase)
Maltose -> Glucose + Glucose (Maltase)
Sucrose -> Glucose + Fructose (Sucrase)
149
Describe the absorption of glucose, galactose and fructose
Glucose and galactose transported into enterocytes by SGLT1, requires Na+
Fructose transported into enterocytes by GLUT5
150
How are monosaccharides absorbed from enterocytes?
Transported into the blood by transporters in the basolateral membrane
151
How are proteins digested and absorbed?
Digested into smaller peptides or amino acids
Small peptides transported into enterocytes by PEPT1, requires H+
Amino acids are transported using a number of different systems
152
Why are drugs not well absorbed?
Hydrophilic, cannot pass membrane so bioavailability
153
How is absorption of drugs optimised during design?
Designed to mimic a natural ligand so they can be transported into cells using uptake transporters
154
How do efflux transporters affect drug bioavailability?
Drugs effluxed out of cell which is detrimental to absorption
155
What efflux transporters recognise multiple drugs structures?
P-gp and BCRP
156
Why can't anti-cancer drugs be given orally?
Effluxed by P-gp transporter but inhibition increases toxicity of drugs
157
Give three examples of anti-cancer drugs
Etoposide
Doxorubicin
Paclitaxel
158
What are the concerns with giving chemotherapy IV?
Cell death at the injection site
| Extravasation may lead to tissue necrosis
159
What is the effect of P-gp inhibitors administered alongside substrates?
Increased plasma conc. of substrate, patient may experience substrates
160
Describe the physiology of the liver
Largest organ in the body
| 2 blood supplies - hepatic artery and portal vein, 80% is from the portal vein
161
What are the functions of the liver?
Storage of glycogen and fat-soluble vitamins
Synthesis of proteins, albumin and clotting factors
Immune functions - T cell proliferation, acute phase protein production
- Clearance and metabolism of drugs and cholesterol
162
Describe the biliary system of the liver
Left and right hepatic ducts lead into common hepatic duct; cystic duct and common hepatic duct lead into common bile duct which then leads to duodenum
Pancreatic duct also leads into duodenum
163
What parameters are included in LFTs?
Bilirubin
Gamma-Glutamyl Transferase (increased after alcohol)
Alanine/Aspartate Aminotransferase
Alkaline Phosphate (not liver specific)
Albumin (synthesis in liver)
Prothombin Time (synthesis of clotting factors)
164
What characterises hepatocellular damage?
Increased ALT
Increased AST
Increased GGT
Increased total bilirubin
165
What is cholestatic damage?
Decrease in bile flow due to blockage of drainage system
166
What characterises cholestatic damage?
Increase conjugated bilirubin
increased alkaline phosphate
Increased total cholesterol
Pruritis (itchy skin)
167
Describe acute liver disease
Self limiting (normally)
Hepatocyte damage or inflammation
Generally caused by drugs or acute viral infection
168
To what extent can drugs damage the liver?
Reversible damage ranging to fatal hepatic necrosis
169
What are the two types of drug reactions and what is the latent period for each?
Type A - Predictable and dose dependent, latent period of hours to weeks
Type B - Unpredictable, less common and independent of dose, latent period of weeks to months
170
What are the two types of acute liver disease?
Acute hepatitis (with jaundice) - Spontaneous recovery and supportive therapy
Acute liver failure - May become hepatic failure and affect whole liver or may become chronic liver disease
- Patient may require liver transplant
171
What are the causes and symptoms of chronic liver disease? What is the disease timeframe?
Alcohol, chronic viral hepatitis (hep C), primary biliary cirrhosis, auto-immune hepatitis, cancer
Fatigue, malaise, fever, N&V, upper right abdominal pain, pruritis, jaundice, oedema
Longer than 6 months
172
What are the three types of alcoholic liver disease? How would they be diagnosed from LFTs?
Steatosis (excessive lipid retention), increased GGT with or without AST
Fibrosis and then cirrhosis (thickening and scarring connective tissue), high prothrombin and low albumin
Hepatitis (and cirrhosis), elevated bilirubin
173
What causes itching in pruritis?
Bile salts collecting under the skin
174
How is cholestatic disease treated?
If cause by gall stones, remove surgically
If cause unknown:
- Anion exchange resins bind bile acids in gut
- Antihistamines for symptom relief
- Topical creams for symptom relief
175
What is Ascites and what are the causes?
Fluid collection in abdominal cavity
Portal hypertension, activation of renin-angiotensin system, decreased oncotic pressure (low albumin)
176
What is the treatment for ascites?
Diuretics:
- Spironolactone 100-600mg OD
- Furosemide 40-160mg OD
- Metolazone if above do not work
Reduce sodium in diet
177
How is ascitic pain treated?
Analgesics:
- Paracetamol (max 2g daily)
- Tramadol
- Opioids WITH CAUTION (decreased clearance)
178
Why can't NSAIDs or anti platelets be used in ascitic pain?
Bleeding risk
179
What is hepatic encephalopathy?
Nitrogenous waste and other toxins reach the brain, causes altered mental state
180
What causes exacerbations of hepatic encephalopathy?
Gi Bleeds
Constipation
Use of opiates
High protein diet
181
How is hepatic encephalopathy treated?
```
Low protein diet
Lactulose - prevents constipation
Neomycin - Peripheral neuropathy
Rifaxamin
Metronidazole
Enemas if unable to swallow
```
182
How are oesophageal varices formed?
Intrahepatic vascular resistance causes portal hypertension along with splanchoic arteriolar vasodilation. Dilation of pre existing vessels and angiogenesis cause formation of varices in stomach and oesophagus
Further increase in portal hypertension causes increase in size of varices, eventually they rupture and bleed (large blood loss)
183
How are varices treated?
Constrict blood flow and reduce portal hypertension
184
How are alcohol and vitamin deficiencies treated?
Chlordiazepoxide
Oral vitamin B and thiamine (or IV pabrinex)
Water soluble menadiol (vit K)
185
What are the different types of viral hepatitis?
Hepatitis A-E
186
How are the different viral hepatitis diseases treated?
Hep A: Supportive treatment
Hep B: Chronic treatment with antivirals (entecavir/tenofovir) and interferon alpha-2a
Hep C: Ribavarin with interferon alpha-2b
187
What is coeliac disease and what are the triggers?
Autoimmune disease - immune system is triggered by wheat proteins
188
What are the symptoms of coeliac disease?
Headaches
Diarrhoea (therefore weight loss and malnutrition)
Stomach Pains
Lethargy
189
How is coeliac disease managed?
Gluten free diet (life long), may include foods with specially modified wheat starch
190
When can prescriptions be given for gluten free foods? How much are they?
Diagnosed with coeliac disease, dermatitis herpetiformis
Standard £8.40 prescription tax
191
When are guidelines for monthly prescribed amounts of GF foods used?
Patients presenting with malnutrition, intractable malabsorption, difficulty swallowing, IBD, bariatric procedures, short bowel syndrome
192
What are the forms of enteral nutrition?
Sip feeds, supplements, nasogastric feeding, PEG/PEJ tubes, distal feeding
193
What are three common causes of stoma care?
Colon cancer
Bladder cancer
IBD
194
Describe the difference between a temporary stoma or permanent stoma
Temporary: Diversion of faeces from surgically rejoined intestine or obstructions
Permanent: Loss of bowl/urinary function due to disease or its treatment
195
How can post-surgical problems arise in stoma care?
Stoma itself or other conditions
196
How are stoma supplies prescribed for and dispensed?
Stoma appliances available for prescription are on drug tariff, stock is then ordered by mail depending on amounts
197
Where is a stoma bag placed?
Just before the section that is removed due to a colostomy procedure
198
What is a common side effect in patients who have undergone a colostomy?
Constipation
199
What are the issues surrounding MR preparations and laxatives in colostomy patients?
GI transit may be rapid
| Laxatives should be avoided due to loss of water and electrolytes
200
How is constipation in colostomy patients treated?
Initially fluid/dietary fibre
| Low dose laxatives used with caution
201
What are the issues with Mg, Al, Ca and Fe in colostomy patients?
Mg - Increased risk of diarrhoea
Al/Ca - Increased risk of constipation
Fe - use I/M administration to prevent loose stools
202
What are the issues with compound analgesics (codeine +) or antibiotics in colostomy patients?
Analgesics may cause constipation
| Antibiotics may cause diarrhoea
203
What are the effects of potassium-sparing diuretics and digoxin in colostomy patients?
K+ sparing diuretic should be avoided due to K+ depletion
| Digoxin may cause hypokalaemia so should be given with liquid K+ supplement to avoid osmotic diarrhoea
204
What problems are associated with the use of a stoma appliance?
Leaking - incorrect stoma size
Skin problems - prevented by cleansing agents, protective creams and sealants
Manual dexterity - May result in reduced ability to change stoma appliance
Odours
205
How can GI conditions affect absorption of other drugs?
May increase or decrease absorbance depending how the drug is absorbed, therefore altering the therapeutic effect
Antacids may interact with other drugs
Omeprazole may block feeding tubes
206
What frequency of bowel movements characterises normal and diarrhoea?
Normal: 3x weekly - 3x daily
Diarrhoea: More than 300g daily, >70% water
207
What are the causes of diarrhoea?
Poor fluid absorption due to infection, IBD
Osmotic effects of unabsorbed foods
Enzyme deficiencies
Gut motility issues from IBD, diabetes, hyperthyroidism, drugs
208
What characterises acute diarrhoea?
3-4 unformed stools per 24 hour period
Usually self-limiting to 3 days
Caused by virus (rotavirus, norovirus, adenovirus)
May affect travellers due to destination or change in diet
209
How is oral rehydration used for treatment in acute diarrhoea?
Replaces electrolyte deficit
Contain alkalinising agent to counter acidosis (dextrose or rice powder citrate/bicarbonate)
Continue with normal volumes of fluid in between rehydration drinks
210
How is loperamide used for treatment in acute diarrhoea?
Decrease gut motility
Reduced opiate activity
Available OTC
211
How are antispasmodics used for treatment in acute diarrhoea?
Symptomatic relief of abdominal cramps
212
What is racecadotril and what is its mechanism?
What patient groups is it used for?
Oral enkephalinase inhibitor
Reduces hypersecretion of water and electrolytes
Used in children of >3months
213
How is the rotavirus vaccine administered in children and why?
Protection against gastro-enteritis
| First dose at 6-15 weeks, second dose at least 4 weeks later
214
How is Kaolin used in diarrhoea?
Absorb toxins to bulk out stool
215
When should patients with diarrhoea be referred?
```
Symptoms lasting >1 week
Patient if young child/baby
Presenting with dehydration or fever
Dark stools/presence of blood
Severe abdominal/rectal pain
```
216
What is pseudomembranous colitis and what causes it?
Swelling/inflammation of large intestine caused by C. difficile overgrowth
Generally result of poor hygiene but may be caused by antibiotic treatment
217
What is the treatment for pseudomembranous colitis?
Cease antibiotic treatment
Patient isolation
Replace fluid and electrolytes
Metronidazole 400mg TDS/Oral Vancomycin 125mg QDS
May use newer antibiotics, probiotics or IV immunoglobulins
218
What two diseases are classified as IBD? Describe them
Ulcerative colitis - Affects lower section of GIT, cured by total colostomy
Crohn's - Incurable, patchy inflammation affecting whole GIT
219
What are the general treatment steps for patients with IBD?
Local corticosteroid/aminosalicylate
Oral corticosteroid/aminosalicylate
Hospitalisation - IV steroid/immunosuppressive treatment
Sulphasalazine is used to maintain remission in UC
220
What parameters should be monitored in patients with IBD?
```
Faecal calprotectin
Stool frequency
Blood/mucus in stool
Temp
CRP
U&Es
```
221
What actions are undertaken in an IBD relapse?
Bed rest
Low residue diet
Monitoring
Corticosteroid use
222
How is constipation classified and what should be done before treating?
Hard, less frequent stools
Increase fluid intake and dietary fibre
Assess cause
223
What are the causes of constipation?
```
Lack of dietary fibre and fluid
Obstructions
Motility issues
Neurological causes
Side effects of drugs
Lifestyle
```
224
How is constipation treated? How do they work?
Bulking agents - Increase in mass stimulates peristalsis
Stimulants - Increase intestinal motility
Osmotic agents - Increase water in large bowel
Softening agents - Promotes bowel movements
225
When may laxatives be used?
Expulsion of parasites
Post MI
Prior to surgery/x-ray
In liver failure
226
What are the functions of the kidney?
Homeostasis - Blood volume and pressure, ion levels, acid-base balance
Excretion - metabolites, chemicals and drugs
Endocrine - Erythropoetin production, vitamin D3 production, Ca2+ regulation
227
Where are the kidneys located?
Back of abdominal wall
228
What are the regions and functional units of the kidneys?
Cortex, medulla and nephrons
229
Describe the functional units of the kidneys and their functions
Glomerulus -> Bowman's Capsule -> PCT -> PST -> LoH -> DCT -> CCD -> MCD -> Bladder
Filtration of the blood - high hydrostatic pressure maintained by different diameter of the afferent and efferent arteriole
230
Describe glomerular filtration
Blood filtered through three layers into bowman's space, where it then enters nephron - capillary endothelium, basement membrane, podocytes of the bowman's capsule
231
How is the rate of glomerular filtration altered? What does it show?
Increases with blood pressure
Defined as volume of fluid entering bowman's capsule with unit time
Can be used to reflect kidney function
232
What is secretion?
Some molecules may be secreted from the vasa recta and enter the nephron further along
Blood may also enter at this point
233
What is reabsorption?
Molecules are reabsorbed from the nephron filtrate into the vasa recta
Includes glucose, amino acids and some drugs
234
What factors influence renal function and how?
Age, disease
Reduced kidney function may reduce rate of elimination
Patients may require lower drug doses
235
What two ways is eGFR measured?
Inulin clearance - Administered IV and freely filtered, not metabolised by kidney therefore amount filtered into Bowman's capsule is amount in urine
Creatinine clearance - Creatinine produced in muscles but freely filtered, ~10% is secreted by nephron BUT does not require IV administration
236
What is the definition of renal clearance and how is it measured?
Volume of plasma completely cleared of a substance with unit time
Cx = [Ux]V/[Px]
237
How are substances secreted from the vasa recta into the nephron tubule?
Uptake transporters in the basolateral membrane removes substances from the blood
Efflux transporters in the apical membrane transport these into the filtrate
238
How is glucose reabsorbed from the kidney filtrate?
Uptake via glucose transporter and reabsorbed into vasa recta
239
Give an example of diabetes treatment and how it works
Dapagliflozin - Blocks SGLT2, preventing glucose reabsorption
240
Give 5 uptake and elimination examples of drugs
Methotrexate - Uptake: OAT1 and OCT1, Efflux: MRP2 and P-gp
Pituvastatin - Uptake: OAT3, Efflux: BCRP
Rosuvastatin - Uptake: OAT3, Efflux: BCRP
Fexofenidine - Uptake: OAT3, Efflux: P-gp
Digoxin - Uptake: OATP1, Efflux: P-gp
241
How is water reabsorbed in the kidneys?
~70% of Na+ is reabsorbed in PCT, some reabsorbed in collecting ducts. Water follows by passive diffusion
242
How is Na+ reabsorbed?
Co-transported with organic molecules (e.g. glucose)
| Coupled with H+ secretion (acid-base balance)
243
Describe the mechanism of acid-base balance in the kidneys
Dissociation of carbonic acid forms H+ and HCO3-, anitporter protein effluxes H+ by uptake of Na+ and HCO3- moves into blood to act as a buffer
244
How is the acid-base balance regulated in the lungs?
Excretion of CO2 from the body
245
What is acidosis and how is it prevented?
H+ build up due to inefficient lung function (due to fibrous tissue formation and inefficient CO2 removal)
Kidneys compensate by increasing H+ secretion to prevent build up and restore normal levels
246
What is the CO2/H+ equilibrium?
CO2+H2O H2CO3 H+ + HCO3-
247
What equation defines the proportion of acid to dissociated acid?
pH = pKa + log([A-]/[HA])
248
How is aldosterone secreted?
Renin-Angiotensin system
Low Na+ sensed by kidney juxtaglomerular cells -> Renin production -> Conversion of angiotensinogen to ATI -> Conversion of ATI to ATII by ACE -> ATII stimulates aldosterone production and secretion from adrenal cortex
249
How does aldosterone increase Na+ levels?
Increased Na+ channels in apical membrane and increased Na+/K+ ATPase in basolateral membrane of cells in collecting duct
250
How do ACE inhibitors prevent sodium reabsorption?
What conditions are they used in?
Prevent conversion of ATI to ATII so no aldosterone secretion
Heart failure and hypertension
251
Give two examples of diuretics and how they prevent water retention
Spironolactone - Aldosterone analogue, prevents Na+ reabsorption by preventing extra channels in collecting duct cell membranes
Amiloride - Binds to and blocks Na+ channels
Both result in Na+ excreted in urine, water is not reabsorbed without sodium due to osmosis
252
How much of the glomerular filtrate is reabsorbed?
~99% - 120L of blood filtered but only 1.5L urine produced every 24 hours
253
What factors affect the number of nephrons?
Age
| Hypertension
254
Describe the different parts and processes of the nephron
Proximal Tubule - Tight junctions between epithelia cells (leaky), secretion of organic acids/bases
Descending LoH - Hypertonicity of interstitial fluid causes water to diffuse out
Ascending LoP - Low water permeability, active transport of Na+ into interstitial fluid
Distal tubule - Impermeable to water, some Na+ reabsorption
Collecting Duct - Water reabsorbed via aquaporins
255
How is water reabsorption in the collecting duct mediated?
Release of ADH from pituitary gland binds to vasopressin receptors, aquaporins in vesicles are inserted into membrane
256
What are the actions of diuretics?
Increase urinary output
Decrease oedema
Reduced plasma volume
257
How do loop diuretics work and what effect do they have on ion reabsorption?
```
Inhibition of Na+/K+/Cl- carrier (ALoH) but Na+/H+ exchanger remains unaffected
K+, Cl-, Ca2+, Mg2+ excreted in urine
Plasma conc. of HCO3- increases
Less uric acid excretion
Vasodilation before diuresis
```
258
How do NSAIDs interact with loop diuretics?
PGE2 inhibits absorption of Na+/Cl-
NSAIDs prevent PGE2 production so opposite diuretic effect
Also competes with diuretic for OAT
259
What are the indications for loop diuretics?
```
Acute pulmonary oedema
Chronic heart failure
Liver cirrhosis
Nephrotic syndrome
Renal failure
Hypertension
Hypercalcaemia
```
260
What are the side effects of loop diuretics?
```
Hypertension
Hypokalaemia
Metabolic alkalosis
Gout
Hearing Loss
```
261
Describe the pharmacokinetics of loop diuretics
Absorbed in GIT
Effect <6hours
Half life 90mins
Albumin binding
262
How do Thiazide and Thiazide-like diuretics work and what effect to they have on ion reabsorption?
Na+/Cl- co-transporter in DCT inhibited
Vasodilation
Same mechanism as loop diuretics
Ca2+ excretion decreased - used in those with a risk of osteoporosis
263
Why does chronic use of thiazide-like diuretics have a limited hypotensive effect?
Decreased blood volume causes increased activity of renin-angiotensin system
264
What are the indications for thiazide-like diuretics?
Hypertension, heart failure, oedema, nephrogenic diabetes
265
What are the side effects of thiazide-like diuretics?
Increased urination frequency
Erectile dysfunction
Hypokalaemia
Impaired glucose tolerance
266
How is hypokalaemia prevented when using diuretics?
Increase dietary intake
K+ supplements
K+ sparing diuretics
267
What type of diuretic is Spironolactone?
K+ sparing diuretic
268
What are the indications of K+ sparing diuretics?
```
Hyperaldosteronism
Ascites
Oedema
Severe heart failure
Left ventricular failure post MI
```
269
What are the side effects of K+ sparing diuretics?
Hyperkalaemia
GI upsets
Menstrual disorders
Testicular atrophy
270
How do osmotic diuretics work?
Filtered to increase osmolarity of filtrate, Na+ reabsorption prevented by dilution
271
What are the varying levels of renal impairment?
Pre dialysis
Haemodialysis/Peritoneal dialysis
Requiring kidney transplant
272
What characterises kidney disease?
Damage for > 3months and GFR >60ml/min/1.73m2
GFR <60ml/min/1.73m2 with or without damage
Function or structure abnormal
Generally alongside other conditions
Not always symptomatic
273
What markers are used to assess renal function or rate of change?
```
Albuminuria
Urine sediment abnormalities
Electrolyte abnormalities
Cellular abnormalities
Structural abnormalities
Previous kidney transplantation
```
274
How is serum creatinine influenced?
Proportional to muscle mass and can be influenced by drugs/diet
275
What is considered when working out eGFR?
Gender, age, creatinine levels, ethnicity (correction factors)
276
When is Cystatin C-based GFR used?
If eGFR (creatinine) is 45-60ml/min for more than 90days and no other marker of CKD
277
What does a urine dipstick test for
Haematuria
| Proteinuria/Albuminuria
278
What are risk factors for CKD?
```
Diabetes
Hypertension
Kidney injury
CVD
Family history
Haematuria detection
```
279
What medications slow disease progression or reduce risk of another disease as a result of CKD?
Glycaemic control
BP control
Statins to prevent development of CVD
280
What are the different stages of CKD and what do they refer to?
Stages 1-4: drop in eGFR
| Stage 5: Consider replacement therapy
281
What are some complications of CKD?
```
Anaemia
Disordered bone metabolism
Osteoporosis
High phosphate
Pruritis
Acidosis
Hypertension
```
282
What causes nausea in CKD?
Build up of toxins
283
What is the main cause of death in acute kidney injury?
Delay in recognition and treatment
284
What is an acute kidney injury?
Rapid reduction in renal excretory function characterised by increased creatinine and reduced urinary output
285
What are the risk factors for acute kidney injuries?
Clinical factors
Co-morbidities
Nephrotoxic drugs
286
How is an acute kidney injury detected?
Increase in serum creatinine by >26mml/L in 48hrs or 50% in 7 days
Urine output <0.5ml/kg/hour for 6hours(adults) or 8hours(children)
Decrease in eGFR by 25% within 7days
287
What are the causes of AKI?
Pre renal - Issues with perfusion
Renal - Affects function of kidney
Post renal - Obstruction of fluid leaving kidney
288
What is the SADMAN check when a patient presents with AKI?
```
Checking for medicines that may cause AKI
Sulphonylureas
ACE/ARB
Diuretics
Metformin
Aldosterone antagonist
NSAIDs
```
289
When should haemodialysis be considered for an AKI patient?
```
In cases of:
Fluid overload
High K+
Pericardial rub
uraemia/encephalopathy
Metabolic acidosis
```
290
List some common nephrotoxic drugs
```
Antibiotics
Chemotherapy
Immunosuppressants
Heavy metals
Statins
Abused drugs
```
291
What is dialysis and what is the difference between haemodialysis and peritoneal dialysis?
Diffusion of molecules across a semi permeable membrane along an electrochemical conc. gradient
Haemodialysis uses semi synthetic membrane
Peritoneal dialysis uses peritoneum
292
How is the gradient maintained in dialysis?
Dialysate flow is in opposite direction to blood flow
293
What is the aim of dialysis and what are the side effects?
Aim is removal of electrolytes
| Anaemia, hypertension, time consuming, infections, clotting problems, pain
294
What are the advantages and disadvantages of peritoneal dialysis?
Slower decline in kidney function but not as efficient removal of electrolytes
295
What are the benefits and disadvantages of organ transplantation?
Better quality of life
Lower morbidity and mortality
Cheaper than dialysis
Requires an organ donor
Immunosuppression from point of transplantation
Chance of organ rejection
296
What combination treatments for immunosuppression are used?
Ciclosporin/Tacrolimus +/-
Prednisolone +/-
Mycophenolate/Azathioprine
297
What are the issues surrounding ciclosporin/tacrolimus/sirolimus?
Narrow TI
| Many drug interactions
298
How does kidney disease affect pharmacokinetics?
Altered GI absorption
Altered 1st pass metabolism
Increased volume from renal failure results in increased volume of distribution - Lower plasma concentration
Drug metabolites may not be excreted
299
What affects the filtration, secretion and reabsorption of the drug?
Water solubility
Protein binding
Molecular size
Distribution
300
What factors affect adherence in kidney disease?
Amount of medicine to take
Cost of medicines
Treatment duration
Side effects
301
Why should opioids and codeine be used with caution in kidney disease?
Morphine renal excreted
| Codeine metabolised to morphine
302
How are patients with kidney disease immunocompromised?
Susceptible to infections
| BP may affect immunity
