Life Support Flashcards
(172 cards)
1
Q
What are the names of the two layers of pleura?
A
Visceral pleura - at the lungs
Parietal pleura - on chest wall
2
Q
What does lung compliance describe?
A
How does the expansive force (transpulmonary pressure) translate to change in volume.
- High compliance = less force required to induce a specific change in volume (↓stiffness)
3
Q
Describe the effect of pulmonary surfactant on lungs
A
Reduces alveolar surface tension and therefore increases lung compliance
4
Q
A 31 year old man is stabbed in the back and suffers a traumatic pneuomothorax, causing atelectasis (collapse) of part of the lung. What changes would you expect to lung volume, pleural cavity
volume and intrapleural pressure in the affected tissue?
a) ↓Lung volume, ↓pleural cavity volume, ↓intrapleural pressure
b) ↓Lung volume, ↓pleural cavity volume, ↑intrapleural pressure
c) ↓Lung volume, ↑pleural cavity volume, ↓intrapleural pressure
d) ↓Lung volume, ↑pleural cavity volume, ↑ intrapleural pressure
e) ↑Lung volume, ↓pleural cavity volume, ↑intrapleural pressure
A
D
5
Q
A 68 year old female patient is attending the clinic to receive the results from a recent respiratory function tests. The doctor interpreting the results observes that the patient’s lung compliance values are very high (the values are also increasing as time goes on).
What respiratory condition would information indicate?
a) Asthma
b) Chronic bronchitis
c) Emphysema
d) Neonatal respiratory distress syndrome
e) Pulmonary fibrosis
A
C
6
Q
A newborn baby develops neonatal respiratory distress syndrome
due to insufficient levels of pulmonary surfactant within the lungs.
What causes the decreased lung compliance observed in such a
patient?
a) Degradation of elastin fibres
b) Deposition of collagen
c) Reduced alveolar surface area
d) Increased surface tension at the air-liquid interface
e) Airway smooth muscle contraction
A
D
7
Q
What is spirometry used for?
A
Measures the volume and flow during maximal expiratory effort after
maximal inhalation
Useful in differentiating between obstructive & restrictive lung disorders
8
Q
What are peak flowmeters used for?
A
Diagnosis of variable airway obstruction & monitoring of treatment success
9
Q
A spirometer shows a patient has a reduced FEV1 & FVC. The FEV1/FVC is normal. What kind of lung disorder?
A
Restrictive lung disease
10
Q
A spirometer shows a patient has a reduced FEV1 & normal FVC. The FEV1/FVC is lowered. What kind of lung disorder?
A
Airway obstruction
11
Q
What may a reduction in transfer factor result show? (respiratory)
A
- Severe reduction in ventilation or perfusion
- Severe emphysema (reduced surface area)
- Heart failure (reduced ventilation
- Pneumonia (reduced ventilation)
- Pulmonary emboli (reduced perfusion)
- Thickening of alveolar-capillary membrane
- Intersitial lung disease e.g. pulmonary fibrosis
12
Q
List some risk factors for asthma
A
Parental asthma; susceptibility genes; infant respiratory virus infection; caesarean; urban dwelling & pollution exposure; poor diet; obesity
13
Q
Show how allergic sensitisation occurs (cellular level) for asthma
A
- Allergen is encountered & processed by adaptive immune system
- Antigen presenting cell** (APC) (e.g. dendritic cell) engulfs & processes allergen - presents antigen to naive Th cell
- (now mature) Th2 cell interacts with B cell, displaying antigen
Interleukins produced by mature Th2 cell also activate eosinophils which proliferate
- IgE antibodies are generated by B cells, immune system ‘primed’
IgE antibodies bind to IgE receptors on mast cells
14
Q
Explain what happens in asthma upon re-exposure to an allergen.
A
1) Allergen binds IgE on mast cells, inducing degranulation
- Inflammatory mediators released - PGs, LTs, chemokines
2) Allergen stimulates further T cell activation, which produce ILs that stimulate eosinophils, which are recruited to airways and degranulate
- Releasing inflammatory mediators - ROS, enzymes, leukotrienes
- Mast cells also induce this
3) Overall resulting in airway inflammation, contraction of smooth muscle, excess mucus secretion
15
Q
Describe the roles of Th2 cells, B cells, mast cells & eosinophils in asthma pathophysiology
A
Th2 - sensitisation - induces B cells to produce allergen-specific IgE.
Inflammation - coordination of immune response by cytokine release (IL4,5,13)
B-cells - allergen-specific IgE production
Mast cells - allergen induced degranulation = release of inflammatory mediators (leukotrienes & prostaglandis)
Eosinophils - cytokine induced degranulation = release of inflammatory mediators (ROS, proteolytic enzymes, leukotrienes)
16
Q
What changes occur to the airways after long-term asthmatic airway remodelling?
A
- ECM deposition & fibrosis
- Epithelium disruption
- Smooth muscle hypertrophy
- Basement membrane thickening
- Excess mucus & goblet cells
- Immune cell infiltration
17
Q
What controls, and which nerves innervate, respiration?
A
Respiratory cenre - ill defined group of neurons in reticular substance of brainstem
Motor discharges travel down the phrenic & intercostal nerves to respiratory musculature
18
Q
What gives input for chemical & neurogenic control of ventilation?
A
PERIPHERAL chemoceptors - aortic arch & carotid bodies
CENTRAL chemoceptors - brain
- Hypothalamus - pain & emotional stimuli
- Limb receptors during exercise
- Juxtapulmonary receptors stimulated by pulmonary congestion
- Stretch receptors in muscles & joints of chest wall
- Consciously induced changes
19
Q
What gives specific substances affect chemical control of ventilation?
A
Rise in CO2 is strongest stimulant (central & peripheral chemoceptors detect this)
Peripheral chemoceptors (aortic arch & carotid bodies)
- Rise in H ions increases ventilation
- Reduced pO2 increases ventilation (peripheral chemoreceptors)
20
Q
Comment on these ABG taken on air:
pH – 7.4 (7.35 - 7.45)
pO2 – 20 kPa (11-13.3kPa)
pCO2 – 5 kPa (4.9-6.1)
HCO3- - 25 mmol/l (22-30)
A
This is impossibe on room air. Must be on O2
21
Q
21yr. Old man - acutely short of breath
pH - 7.49 (7.35 - 7.45) pO2 - 7.0 kPa (11-13.3kPa) pCO2 - 3.0 kPa (4.9-6.1) HCO3- - 24 mmol/l (22-28)
How do you interpret these blood gases?
How would you treat this patient?
A
Type I respiratory failure, respiratory alkalosis. Treat with high flow Oxygen
Potential causes include acute asthma, PE, COPD
22
Q
73 year old woman admitted with increased confusion:
pH - 7.25 (7.35 - 7.45)
PaO2 - 7.1 kPa (11-13.3kPa)
PaCO2 - 9.2 kPa (4.9-6.1)
HCO3- - 29 mmol/l (22-28)
How do you interpret these blood gases?
A
Respiratory acidosis - Type II resp failure.
Partial metabolic compensation
23
Q
21 year old woman admitted with breathlessness:
pH - 7.15 (7.35 - 7.45)
PaO2 - 14.0 kPa (11-13.3kPa)
PaCO2 - 2.9 kPa (4.9-6.1)
HCO3- - 14 mmol/l (22-28)
How do you interpret these results?
Why is she breathless?
A
Metabolic acidosis with attempted respiratory compensation.
24
Q
What are the main differences between type I & II respiratory failure?
A
Type I:
- Hypoxic; pCO2 < 6.5kPa
- Increased resp rate leads to fall in CO2
- VQ mismatch
Type II:
- Hypercapnic; pCO2 > 6.5kPa
- Ventilatory failure, insufficient to excrete CO2
25
What characterises asthma?
Classical symptoms (more than one of wheeze, chest
tightness, breathlessness or cough) and variable airflow obstruction.
Airway hyper-responsiveness and airway inflammation are components of the disease.
26
What are the clinical features of asthma?
- Cough; wheeze; chest tightness; sputum production; dyspnoea; reduction in exercise tolerance
- Variability, particularly diurnal
- Throughout day if severe
- Associated with triggers i.e. exerxise, allergen exposure
- May see no symptoms
27
Give two specific examples of how asthma can be diagnosed.
Spirometry - FEV1 pre & post bronchodilator - Dx if 12% improvement & 200ml vol increase
PEFR - Dx if mean variability >20%, or >15% dirunal variation
28
What is a challenge test (asthma)
Challenge test for bronchial hyper-responsiveness - done if spirometry & peak flow charts normal.
Histamine (or other allergen inducer) challenge. The PC20 is calculated - dose of agent provoking 20% fall in FEV1
If PC20 is <8mg/ml, asthma can be diagnosed
29
What are the aims for chronic asthma management?
- No daytime symptoms
- No night-time awakening due to asthma
- No need for rescue medication
- No asthma attacks
- No limitations on activity including exercise
- Normal lung function (in practical terms FEV1 and/or PEF>80% predicted or best)
- Minimal side effects from medication
30
What are some signs that acute asthma is life-threatening?
PaCO2 normal or raised. Altered conscious level, exhaustion, cyanosis
31
How should acute asthma be managed? First things.
- Oxygen to maintain spO2 94%+
- Bronchodilator (salbutamol, SABA)
- Ipratropium bromide via nebs
- Prednisolone tablets
- No sedatives
32
A patient with high blood pressure is prescribed the Ca channel blocker
amlodipine. What best describes how this drug produces a reduction in
blood pressure?
a) Increases parasympathetic activity
b) Increases vasodilatation
c) Reduces blood volume
d) Reduces contractility
e) Reduces heart rate
B
33
What best describes the process increased by stimulation of B1
adrenoceptors to enhance contractility?
a) Action potential duration
b) Ca-ATPase
c) Ca-induced Ca release
d) K channel activity
e) If channel activity
C
34
What are the main ways in which cardiac output is affected by sympathetic activity? (no mechanisms)
HR increase (chronotropic effect)
Contractility increase (inotropic effect)
Venoconstriction (Starling's law)
TPR increase
35
Outline the chronotropic effect of sympathetic activity on the heart
SA node! increases HR.
https://www.notion.so/Physiology-pharmacology-of-ANS-on-heart-blood-vessels-fb242dffd419468fbc58a0c21dec4211#3a96915ef89146d9b98e1a55dec42b23
NA stimulates B1 adrenoceptor to produce cAMP from ATP, which increases activity of the If channel, generating Na influx.
Na influx means more fequent depolarisations can occur, increasing heart rate.
36
What are the main receptors of ANS control in the heart & blood vessels? Parasymp or symp, and their specific locations.
M2 (para) & B1 (symp) - SA & AV node
B1 (symp) - ventricles
a1 (symp) - blood vessels
37
What directly maintains blood pressure?
Contraction of the left ventricle, resistance of small blood vessels, arterial walls, and volume & viscosity of blood
38
Give the BP ranges for optimal, normal, high, & grade 1-3 hypertension
(Systolic, diastolic)
Optimal = <120, <80
Normal = <130, 85
High = 130-9, 85-9
Grade 1 (mild) = 140-159, 90-99
2 (moderate) = 160-179, 100-9
3 (severe) = >180, >110
39
How do changes in the following affect BP:
SV, TPR, & HR
Lowers BP:
Low SV
Slow or very fast HR
Reduced TPR
Raises BP:
High SV
High TPR
40
What is a normal blood volume, distribution, & circulation capacity.
Normal volume - 5-6L
Normal capacity - 25-50L
81% of blood is in veins, 13% in arteries & 6% in capillaries.
41
Control of blood pressure involves which systems?
CV, renal, endocrine & sympathetic nervous systems
42
How do the kidneys regulate blood pressure?
Must retain 99.5% of filtered sodium to maintain BP.
- Proximal tubule Na/H exchanger - 60% absorption
- Ascending loop of Henle - Na-K-2Cl cotransporter - 30%
- DCT - Na-Cl co-transporter - 7%
43
What is the RAAS? Give an overview.
RAAS is a hormone system within the body that is essential for the regulation of blood pressure and fluid balance.
Angiotensinogen -> Angiotensin I (+Renin)
Angiotensin I -> Angiotensin II (+ACE Chymase)
Angiotensin II induces aldosterone release & vasoconstriction.
44
What is angiotensin II, & its function?
Most powerful vasoconstrictor, fomed by action of ACE on angiotensin I.
Also stimulates secretion of aldosterone, resulting in water & Na retention
45
What are the effects of epinephrine on blood pressure, & how is it released?
Released by adrenal medulla in response to sympathetic activity
- Increases mean arterial pressure
- Acts on heart - Increases HR & SV
- Acts on smooth muscle of arterioles & veins to increase TPR
46
What are the main effects of vasopressin? What stimulates its release?
Enhances water retention in collectinf duct.
Secretion from Pituitary increased by drop in blood volume and/or
Increase in osmolality
47
What are the main effects of ANP? What stimulates its release?
Atrial natriuretic peptide - increases salt excretion via kidneys by reducing water reabsorption, relaxes renal arterioles & inhibits Na reabsorption.
Released in response to stimulation pf atrial receptors.
48
Explain what would happen when blood pressure drops, with regards to baroreceptors.
Baroreceptors in aortic arch & carotid sinus detect drop in BP -> afferent signals in the CNS -> SNS activated -> HR, contractility rise & vascular smooth muscle contraction
Heart & pulmonary artery detect drops in volume -> activation of cardiopulmonary receptros -> SNS activation
49
Outline the inotropic effect at myocytes upon B1 adrenoceptor stimulation
1) B adrenoceptor (GPCR - Gas) stimulated, which converts ATP to cAMP with adenylate cyclase
2) cAMP causes an increase in PKA, which:
a) stimulates VGCCs -> Ca influx
b) Ca release from SR by acting at RyR
c) further release from SR by CICR
3) Ca binds to troponin, increasing crossbridge formations, INCREASING CONTRACTILITY
50
What controls total peripheral resistance? (ANS)
- A & NA release from adrenal medulla via symp nerves, acting A1 adrenoceptors on VSMCs
- NA& A also induce venoconstriction, increasing SV
51
Outline mechanism of A1 adrenoceptor stimulation at vascular smooth muscle cells
1) A adrenoceptor (GPCR - Gaq) stimulated, which converts PIP2 to IP3 & DAG using PLC
2) DAG stimulates Na channel, influx causes depolarisation
a) Depolarisation causes Ca influx by VGCC
3) IP3 stimulates Ca release from SR
4) Overall effect of [Ca] increase causes contraction by myosin light chain kinase
52
Briefly describe parasympathetic activity on the heart (blood pressure). NT release & effects.
Release of ACh from vagus nerve controls CO by acting at M2 receptors
-Decreased freq of pacemaker potentials at SA node
- Decreased conduction through AV node
53
Describe how baroreceptors detect and deal with changes in posture
Decreased cardiac output is detected by theshold detectors, which reduces stimulation of afferent fibres. This induces Sympathetic nerves, and inhibits vagus nerve (parasymp). This has the effects of increasing HR via SA node, increasing venoconstriction & TPR.
54
What is bioavailability? (Pharm)
Bioavailability: which refers to the proportion of the administered dose of a drug that reaches the systemic circulation (unaltered)
55
What is 'apparent volume of distribution? (Pharm)
A mathematical construct that describes the volume of fluid that would be required to contain the drug, if it were at the same concentration as measured in plasma
56
Routes of administration: what is meant by Buccal, sublingual, subcut, intradermal & intrathecal?
Buccal - between gum & cheek
Sublingual - under tongue
Intradermal - in the skin
Subcutaneous - under the skin
Intrathecal - into cerebrospinal fluid
57
What is meant by drug distribution? (ADME)
How drugs are distributed between body compartments, both in terms of the extent to which they penetrate different compartments, and the rate at which this occurs.
58
What does the apparent volume of distribution tell us?
- How well distributed the drug is
- How the drug is distributed (see table)
- Calculation of loading dose to obtain a given plasma conc
- Determines how quickly drugs will be eliminated (high = slow, e.g.concentrated in fat)
59
What are the functions of the pericardium?
- Restrict excessive movements of the heart
- Serve as a lubricated contained in which different parts of the heart can contract
60
Show & describe membrane potential at the pacemaker
https://www.notion.so/The-Cardiac-Cycle-87e3ba3911264d9d9e5f628f3d43972a#44d443084a874de2add132e96d6b9916
Resting membrane potential is negative.
0) Depolarisation - VGCCs open, rapid influc of Ca causing rapid depolarisation
3) Repolarisation - VGCCs close, activation of V-gated K channels -> K efflux
4) Repolarisation - membrane repolarises below If threshold (-40mV)
61
What best describes the stage in the cardiac cycle that begins with the S1 heart sound?
a) Atrial contraction
b) Diastole
c) Ejection
d) Isovolumetric contraction
e) Ventricular refilling
D)
62
Which best describes the function of A-V node?
a) Coordinates ventricle filling
b) Contains gap junctions
c) Determines contractility
d) Generates pacemaker potentials
e) Speeds up conduction
A
63
Outline the route of conduction through the heart, start to finish.
SA node -> atria (via gap junctions) -> AVn -> Bundle of His (L&R bundle branches) -> Purkinje fibres through ventricles, beginning at apex
64
What is meant by isovolumetric contraction?
Stage in cardiac cycle when pressure in ventricles > atria, valves open to arteries & ejection begins
65
List some causes of secondary hypertension
- Coarctation of aorta
- Renal & renal vascular disease
- Adrenal disease
- Cushings
- Primary hyperaldosteronism
- Pregnancy
- Drugs
- Oral contraceptive pill
- HRT
66
What are some causes of essential hypertension?
High: BMI; alcohol, salt, fat intake
Low: physical activity, fibre, potassium
67
What are the main drug classes used to treat hypertension?
A - ACE inhibitors
B - Beta blockers
C - Calcium channel blockers
D - Diuretic (thiazide)
Others:
- Alpha blockers
- Angiotensin II receptor blockers (antagonist) (ARBs)
- Centrally acting (imidazoline I1 receptor antagonist)
68
Outline the NICE guidelines for hypertension management
https://www.nice.org.uk/guidance/ng136/resources/visual-summary-pdf-6899919517
- Under 140/90 = fine, check every 5 years
- 140/90-179/119 - ABPM/HBPM, investigate for organ damage & assess CVD risk
- 135/85-149/94
- >40 - lifestyle advice & discuss drug treatment
- <40 - specialist evaluation of 2ndary causes
- 150/95+ (stage 2)
- Lifestyle & drug treatment
69
What treatment options would be considered in a pt with hypertension & high CVD risk?
BP lowering treatments (small doses of multiple Rx)
Cholesterol-lower treatment
'Healthy heart' diet
Smoking cessation
70
ACE inhibitors - mechanism & indication?
First line against hypertension, in lower risk indivduals. Blocks the conversion of angiotensin I -> II, which is a vasoconstrictor and stimulates aldosterone secretion. Overall, reduces BP
71
Draw out & label the ECG waveform, and what each section represents (basic)
- P wave - atrial depolarisation
- PR segment - AV node delay
- QRS complex - ventricular depolarisation (atria repolarising simultaneously)
- ST segment - time during which ventricles are contracting & emptying
- T wave - ventricular repolarisation
- TP interval - time in which ventricles are relaxing & filling
72
Draw out the LV pressure changes. Include valve opening/closing points, aortic, LV & atrium pressure.
https://www.notion.so/The-Cardiac-Cycle-87e3ba3911264d9d9e5f628f3d43972a#17b051c51c9d45d18bbfb5a86e809099
73
What causes an increase in jugular venous pressure?
Raised pressure in r atrium (e.g. from R-sided HF), less blood is ejected from R ventricle, so higher afterload, atrium pumping against greater pressure.
Venous distension is increased as a result
74
What are the four heart sounds, and what do they represent?
S1 "Lub" - closure of tricuspud/mitral valves at beggining of ventricular systole
S2 "dub" - closure of aortic/pulmondary valves at end of ventricular systole
S3 - occasional - turbulent blood flow into ventricles, detected near end of first 1/3 of diastole, especially in older people
S4 - pathological in adults - forceful atrial contracion against a stiff ventricle
75
What values denote respiratory failure, and its' types?
Resp failure exists when paO2 <8kPa
Type I (hypoxic) - pCO2 < 6.5kPa
Type II (hypercapnic) - pCO2 > 6.5kPa
76
What are the different types of hypoxia?
Hypoxic hypoxia - low O2 tension
Hypoxaemic hypoxia - low blood content
Circulatory hypoxia - low CO & delivery
Histotoxic hypoxia - poor usage of O2 by tissues (mitochondria)
77
What are some causes of hypoxic hypoxia?
Lack of O2 in atmosphere; airway obstruction; hypoventilaion; VQ mismatches (shunt perfusion or alveolar pathology)
78
What are some causes of hypoventilation?
Coma, COPD, obesity, neuromuscular diseases, brainstem & C-spine injuries
79
List some causes of VQ mismatch
Shunt perfusion
- Pneumonia
- Pul oedema
- Pul fibrosis/ILD
- Airways disease
Deadspace ventilation:
- Pulmonary embolus
- Pneumothorax
- Right to left shunt
80
What are some causes of hypoxaemic hypoxia?
Low Hb, abnormal Hb (SS, thal), other substances bound to Hb (CO, methemoglobinaemia)
81
What is circulatory hypoxia? List some causes.
Blood content is fine, but cardiac output is low, & delivery inadequate as a result.
Causes:
- Shock states
- Cardiac failure
- L->R shunting
- Can be global or focal
82
What is histotoxic hypoxia, and what are some causes?
Inability to use oxygen for tissue metabolism. Causes include sepsis, drugs, and cyanide poisoning
83
What are the principles of treating respiratory failure?
- Correcting hypoxaemia by increasing inspired O2 to maximum
- Identifying & treating the precipitating cause
- Instituting respiratory support if necessary
- Invasive/non-invasive
84
What are the indications for intubation?
Inability to protect airway; failure of ventilation; failure of oxygenation; anticipated need for ventilation
85
What, on an ABG, indicates need for ventilatory support?
High paCO2
86
A pt in respiratory failure is given O2 and their hypoxia resolves. What is the most likely cause?
VQ mismatch
87
Describe the three phases of haemeostasis
Primary haemostasis (platelet plug)
- Vasoconstriction (immediate)
- Platelet adhesion (seconds)
- Platelet aggregation & contraction (minutes)
Secondary haemostasis (coagulation)
- Activation of coagulation factors (seconds)
- Formation of fibrin (minutes) to stabilise plug
Fibrinolysis
- Activation of fibrinolysis (minutes)
- Lysis of the plug (hours)
88
Describe the function of endothelium in haemostasis in RESTING state and the mediators involved.
Antithrombotic (resting state):
Prostacylin/NO/ADPase - inhibit platelet activation
TPa - modulation of fibrinolysis
TFPi/thrombomodulin/heparin sulfate - inhibition of coagulation
89
Describe the function of endothelium in haemostasis in ACTIVE state and the mediators involved.
Prothrombotic (active state)
- Tissue factor - released following endothelial damage
- VW factor - Platelet adhesion & aggregation
- PAi-1 - inhibits fibrinolysis
90
Describe the activation of platelets:
- Platelet activators
- Surface changes
Platelet activators: thrombin, TXA2, ADP, collagen
Surface changes - activates glycoprotein IIb-IIIa
- Secretes ATP, ADP & Ca
- Thrombin generation
- Alpha-granule secretion - coagulation factors & proinflammatory factors
- Shape - change spreads out
90
Describe the activation of platelets:
- Platelet activators
- Surface changes
Platelet activators: thrombin, TXA2, ADP, collagen
Surface changes - activates glycoprotein IIb-IIIa
- Secretes ATP, ADP & Ca
- Thrombin generation
- Alpha-granule secretion - coagulation factors & proinflammatory factors
- Shape - change spreads out
90
Describe the activation of platelets:
- Platelet activators
- Surface changes
Platelet activators: thrombin, TXA2, ADP, collagen
Surface changes - activates glycoprotein IIb-IIIa
- Secretes ATP, ADP & Ca
- Thrombin generation
- Alpha-granule secretion - coagulation factors & proinflammatory factors
- Shape - change spreads out
91
Where are platelets destroyed?
RE system in spleen
92
What is Von Willebrand factor & its functions?
Glue-like factor required for platelet plug formation.
Serves as a bridge between platelets & injury sites (binds to collagen). Prevents excessive blood loss.
VWf binds to glycoprotein complex IbVIX on platelet surface.
Carries factor VIII which is vital for development of fibrin strands, which strengthen platelet plug.
Also involved in angiogenesis
93
What allows platelet aggregation to occur?
GPIIb-IIa - receptor ligand that when becomes active is able to bind ligands (from other platelets)
94
What is Petechiae?
Pinpoint, round spots that appear on skin as a result of bleeding from platelet disfunction or thrombocytopenia
95
Outline how a platelet plug is formed
1. VWf binds to collagen on surface of endothelium
2. VWF binds GPIb on platelet, anchoring to endo-wall. GPIIb-IIIa also activates, linking platelets together
96
What is Glanzmann thrombashenia?
Defect in GPIIb/IIIa complex arising from genetic mutations can impair both platelet recruitment & adhesion.
GT is a bleeding disorder caused by dysfunction of GPIIb/IIIa protein. Ability to form effective platelet plug is poor
97
Where are most anticoagulant factors synthesised? List the bodies main ones.
Liver. Dysfunction therefore can cause bleeding issues.
TFPI, , APC, antithrombin (IXa, Xa & thrombin)
98
Outline the extrinsic pathway of coagulation
- Damage to the blood vessel means that factor VII exits the circulation into surrounding tissues
- Tissue factor (factor III) is released by damaged cells outside the circulation
- Factor VII and factor III/TF form a complex, known as the TF-VIIa complex.
- TF-VIIa then activates **factor X** into its active form, factor Xa
- In conjunction with factor Va, this triggers the formation of thrombin from prothrombin
- Common pathway next
99
Outline the intrinsic pathway of coagulation
- Factor XII is activated once it comes into contact with negatively charged collagen on the damaged endothelium, triggering the cascade
- Along with clotting factors, platelets form a cellular ‘plug’ at the site of injury. These platelets also release mediators that faciliatate further clotting, including Factor VIII.
- Factor IX combines with **Factor VIII** to form an enzyme complex that activates factor X, which along with factor Va, stimulates the production of thrombin
100
Outline the common pathway of coagulation
- activated factor X causes a set of reactions resulting in the inactive enzyme prothrombin (also called factor II) being converted to its active form thrombin (factor IIa) by Prothrombinase.
- The thrombin then converts soluble fibrinogen (also refereed to as factor I) into insoluble fibrin strands. The fibrin strands which comprise the clot are stabilised by factor XIII.
101
Outline the process of fibrinolysis
- The endothelial cells of the blood vessel wall secrete tissue plasminogen activators (tPAs) which convert the precursor plasminogen into plasmin.
- Plasmin subsequently cleaves the fibrin within the thrombus, leading to its degradation
- Including d-dimer
- Fibrin degradation products (FDPs) are generated if non-cross linked fibrin or fibrinogen is broken down
102
What are some signs of clotting disorders?
Ecchymosis (easy bruising) - increased fibrinolytic factors & decreased coagulation
Haemarthrosis - deformed joints, hallmark of haemophilia
103
What is PT?
Prothrombin time - sensitive to factor VII (short half life) in extrinsic pathway.
Driven by tissue factor - stimulates clotting pathway, time taken measured
104
What is APTT?
Activated partial thromboplastin time. Sensitive to intrinsic pathway. Contact activated. Main conditions resulting in abnormal APTT include haemophilias & VWf disease
105
What is TT?
Thrombin time - sensitive to defects in conversion of fibrinogen to fibrin (common pathway)
106
What are the three main indications of anticoagulants?
Stroke prevention (70%)
VTE treatment & prophylaxis (20%)
Arterial thrombotic disease (10%)
107
What is the mechanism of action of heparin?
Binds to & activates antithrombin, which inhibits factor Xa & thrombin
108
List some DOACs
Direct Xa inhibitors - Rivaroxaban, apixaban, fondaparinux
Thrombin inhibitor - dabigatran
109
List the main clinical differences between unfractionated heparin & low molecular weight heparin
UFH - half life 1.5 hours (so must give more often). APTT ratio must be done to monitor anticoagulant. IV infusion.
LMWH - Half life 12 hours, no monitoring requied & more stable bioavailability. Renal clearance. No full reversal agent (Is for UFH)
110
What is the mechanism of Warfarin?
Blocks recycling of vitamin K by inhibiting vitamin-k-epoxide reductase
Vitamin K is required for carboxylating proteins to become active: Factors VII, IX, X & II, and proteins C&S
111
Describe the initial procoagulative effect of warfarin
Anticoagulative factors affected (protein C&S) have a shorter half life than some of the other factors, so initially heparin is used alongside to ensure anticoagulant effect
112
Describe the pharmacokinetics of warfarin
Good bioavailability - rapidly absorbed, oral.
Half life 36-42 hours. Once stabilised, monitoring required every few weeks (& initially)
Eliminated by the liver.
Dose varies widely between individuals - sensitive to diet, other drugs, ethnicity, and age
113
What is INR?
International normalised ratio.
Prothrombin time ratio, corrected by international sensitivity index (ISI). Higher INR = higher risk of bleeding.
Usually want ~ 2 (2x as long to clot)
114
How is Warfarin reversed, and why would this be done?
Reversal needed due to major bleed.
Vitamin K Koniakon, prothrombin complex concentrate.
Fresh frozen plasma, & Omit further anticoagulation
115
What are some side effects & contraindications of Warfarin?
- Bleeding (RFs >70yo, INR >4.9, first 3/12 of Rx, comorbid disease)
- Skin necrosis due to protein C deficiency (if not given alongside heparin)
Contraindication:
- Pregnancy - passes placenta, can cause bleeding in baby
116
What are some advantages of DOACs?
Oral, rapid onset/offset of action.
Little to no food or drug interactions.
Predictable anticoagulant effect, so no routine monitoring required.
117
What are some considerations and contraindications of DOACs?
Contraindication - obesity >40BMI or >120kg
Hair loss is a common side effect, and has renal excretion
118
PE - Describe the changes that occur to the R side of the heart
1) Raised pulmonary pressure (acute cor pulmonale) ->
2) increased pressure in right ventricle at end-diastole, which dilates & leads to tricuspid incompetence.
3) This causes increased atrial pressure which leads to elevated JVP
119
PE - Describe the changes that occur to the L side of the heart
Due to the raised pulmonary artery pressure, there is less blood getting to the left atrium from the RV via the lungs
- This leads to a **reduced LV stroke volume & tachycardia
- If the RV pressure is very high, the interventricular septum may impinge on the LV cavity leading to further compromise on LV function
120
What are the potential causes of a third heart sound?
reverberation of blood rapidly filling the ventricles from the atria (volume overload) or increased transvalvular flow (tricuspid regurgitation)
121
What changes can be seen in a PE ECG?
Often no change. Sinus tachycardia common.
Sometimes SI QIII TIII
Lead I - deep S wave
Lead III - pathological Q wave & T wave inversion
122
What are the main causes of VTE?
Virchow's triad
1) Reduced rate of blood flow
- Immobility, HF
2)Increased coagulability of blood
- Severe injury, cancer treatment, pregnancy, COCP, HRT, dhydration, hereditary thrombophilias
3) Damage to venous endothelium
- Trauma. obesity
122
What are the glucose requirements for a near-term foetus?
~5g glucose/kg/day
122
List the actions of insulin in an adult and foetus
In adults:
- Increased glucose uptake in muscle, fat & liver
- Decreased lipolysis, glucogenogenesis, & ketogenesis
In foetus insulin acts as a growth factor & increases adipose tissue stores
123
What are catecholamines?
Hormones made by your adrenal glands. Released into the body in response to physical or emotional stress. The main types of catecholamines are dopamine, norepinephrine, and epinephrine
124
At birth, what induces the start of catabolic processes?
Catabolic processes here are gluconeogenesis & glycogenolysis.
Abrupt cessation of transplacental flow of nutrients, and stress from birth induces huge surge in catacholamines, which switch on the mentioned processes
125
Where do babies get their energy from in the 24 hours after birth, and why?
Newborns must initially meet metabolic demands from body stores. (gluconeogenesis, lipolysis & beta oxidation)
This is because the average intake of colostrum is only ~7mls per feed in first 24 hours.
126
How do babies protect themselves from hypoglycaemia?
Management of supplies:
- Astrocyte glycogen stores
- Use of alternative cerebral fuels - ketone bodies
Managing demand:
- Brain is highest proportion of resting energy expenditure, but CMR is only 30% of adult value
127
What are the main issues/considerations of a preterm/IUGR baby in terms of nutritional requirements?
- High demands - especially brain
- Small nutrient stores
- Immature metabolism
- Establishment of enteral feeding delayed (preterm)
- Poor fat absorption (preterm)
128
What is congenital hyperinsulinism? What effects does this have?
Diabetic mother with high maternal glucose -> high foetal glucose.
This causes fetal & neonatal hyperinsulinism.
Neonatal macrosomia & hypoglycaemia are common effects of this.
(macrosomia = larger than 4.45kg baby)
129
List some causes of neonatal hypoglycaemia (inborn errors of metabolism)
Glycogen storage disease (type I)
MCADD (medium acetyle-CoA dehydrogenase deficiency)
Galactosaemia
Maple syrup urine disease
130
What is glycogen storage disease (type I) in neonates, and what are the effects of this?
- Deficiency of glucose-6-phosphatase (needed for conversion of G6P to glucose)
- Hypoglycaemia & lactic acidosis in newborn
- Hepatomegaly in older child
131
What is MCADD?
Medium chain acetyl CoA dehydrogenase deficiency.
A disorder where the body is unable to break down medium chain fatty acids into acetyl-CoA (see beta oxidation of fatty acids)
- This means reduced ability to tolerate fasts
- Also part of newborn blood spot screening
132
What is galactosaemia? (neonates)
- Lactose in milk is broken down into glucose or galactose
- Galactose is then converted into glucose
- Absence of any key enzymes causes the disease
- Usually GALT
133
What is maple syrup urine disease (neonates)? What is the presentation?
- Inability to metabolise branched chain amino acids
- Leucine, isoleucine, valine
- Leads to build up of these amino acids & their byproducts
- Part of newborn blood spot screening
- Presents with hypoglycaemia & acidosis within first few days of life
134
What two main things affect O2 & CO2 requirements?
Physical activity - affects O2 demand & CO2 production
Infection, injury, or metabolic dysfunction - increases oxygen consumption
135
How is breathing initiated? (neurogenic)
Breathing is initiated by neural activation of respiratory muscles, which provide the movement required for ventilation
- Respiratory muscles consist of skeletal muscle, so they require neural inputs/stimulation to contract
- Innervation from motor neurons synapsing from descending spinal tracts provide the contractile signal.
136
List the muscles/mechanisms used in inspiration & expiration. Divide into quiet breathing, & increased ventilation.
Divide increased ventilation into respiratory & accessory muscles
INSPIRATION
Quiet - diaphragm
Respiratory (+vent) - external intercostals
Accessory - pectorals, sternomastoid & scalene
EXPIRATION
Quiet - elastic recoil
Respiratory (+) - elastic recoi & internal intercostals
Accessory - abdominals
137
What are the key cell groups in the respiratory centre of the brainstem? What does each control?
PRG (pontine respiratory group) - higher control
DRG (dorsal resp group) - inspiratory output
VRG - (ventral resp group) - expiratory output
138
How do central respiratory chemoreceptors (CRCs) work?
Predominant over peripheral chemoceptors, CRCs detect pH within cerebrospinal fluid as a way of indirectly monitoring arterial CO2 (H+ cannot cross blood-brain barrier due to being polar).
1. CO2 diffuses from arterial blood across blood brain barrier into CSF
2. Reacts with water in spinal fluid:
3. Produces carbonic acid & hydrogen ions
4. Activates CRCs
5. Stimulates ventilation increase
139
Describe the changes to ventilation that occur during sleep.
Lower metabolic rate = ↓respiratory demands
- Postural changes alter mechanics of breathing
- ↓SNS & ↑PNS tone = ↓HR, BP & CO.
- ↓tidal volume, ↓breathing frequency, ↓minute volume ↓SaO2 (≈96%), ↑PaCO2 (≈7kPa)
- ↓upper airway calibre
140
What is central sleep apnoea? What characterises it, and how is it investigated?
Temporary cessation of breathing during sleep caused by dysfunction of the processes that initiates breathing.
Characterised by >5 episodes per hour lasting >10 seconds. Durations of apnoeas may be as long as 90 seconds and the frequency of episodes as high as 160 per hour. Investigated by polysomnography.
141
What are some causes and effects on health of central sleep apnoea?
Health: tiredness (poor sleep quality), CV complications (stress & +SNS tone), metabolic dysfunction.
Causes: stroke, drugs (e.g. opioids), central hypoventilation syndrome (Ondines curse), neonates, altitude
142
Describe the mechanism of Cheyne stokes respiration
Hypercapnia & hypoxaemia caused by altitude, HF, cardiorespiratory dysfunction.
Compensatory hyperventilation leads to hypocapnia & alkalosis, DECREASING respiratory drive, compensatory hypOventilation. This increases hypercapnia & hypoxaemia further - positive feedback
143
What are the vitamin K-depenant clotting factors?
1972!
10, 9, 7 & 2
144
What are the four types of MI that can occur?
Type I - plaque rupture event causing reduced coronary artery flow resulting in ischaemia
Type II - Imbalance between demand & supply (Common in sepsis)
Type III - Pts who suffer cardiac death, die before blood samples or biomarkers can be obtained etc
Type IV - in operations
145
What are the RFs for CHD?
Non-modifiable - age, gender, genes, ethnicity
Modifiable - High BP, smoking, DM, physical inactivity, obesity, high blood cholesterol
146
Describe stable vs unstable angina
Stable - in early stages (of CHD) will hear of predictable pain on exertion
- Rest helps - shouldn’t persist for longer than 20 mins
- At this stage, modifying risk factors is treatment
Unstable - chest pain occurs randomly, inc at rest. Isn't resloved by resting for 20m.
Now considered ACS & risk of mortality is higher (than stable)
147
Describe the difference between angina and non-cardiac chest pain
Angina - squeezing chest, heaviness, pressure, burning, tightness. 3-15m
Radiation to shoulder, neck, jaw
Non-cardiac - pleuritic, sharp, knife like, choking. Positional. Random onset & duration
148
STEMI indicates an MI has occured. STEMI in which leads = where on heart was the MI?
Lateral (circumflex & diagonal)- I, aVL, V5-6
Anterior (LAD) - V1-V4
Inferior - II, III & aVF
149
STEMI - What are the immediate actions that should be taken?
Monitoring & defib
IV access & blood tests
O2 as required
Analgesia (morphine with anti-emetic)
Antiplatelet therapy (aspirin & ticragrelor)
Reperfusion (potentially)
150
What is the mechanism of action for aspirin?
Aspirin is an NSAID, which Irreversiby inhibit COX
COX leads to formation of PGs which cause inflammation, swelling, pain & fever
Also required to make precursor of thromboxane in platelets - for platelet aggregation
151
When is surgical intervention appropriate for a STEMI? What is the alternative?
If presenting within 12h of symptoms & PCI can be done within <2h. CABG if this fails
If cannot give PCI, do fibrinolysis
152
What is given for post-MI medical therapy?
B-blockers
ACE inhibitors
Statins
Dual antiplatelet therapy
153
What is troponin, and its types? When would it rise & fall following an MI?
Protein released from myocytes when irreversible damage occurs.
Troponin I is more specific to cardiac than toponin T (non-CV death)
Level depends on severity & size of infarct (good indicator of prognosis)
Doesnt rise above normal in first 6 hours, peaks 24-48h & normal after ~1 week
154
What is CK-MB used for in MIs?
As a marker of repeat MIs, as peaks at 1 & normalises after 2-3 days
Tn can stay high for 1 week plus
155
What is myoglobin used for in MIs?
Only as early indicator as rises after 1h but normalises after a day
156
How is stable angina managed?
GTN spray
Long term - Beta blockers & calcium channel blockers
Secondary prevention - aspirin, ACE-i
157
How is an NSTEMI managed?
Stabilise pt & ruptured plaque first, consider reperfusion later.
BATMAN
(BBs, aspirin, ticagrelor, morphine, ACE-i, Nitrates)
For reperfusion:
Risk stratification - grace score
If unstable (ongoing chest pain) may need urgent revascularisation (PCI)
158
What lifestyle advice would you give to someone who has just suffered from an MI?
Alcohol (-)
Phys activity (30m/day to breathlessness)
Smoking cessation
Weight management
(Maybe only primary) cholesterol reduction
159
Describe the histological effects on cardiac tissue up to a month following an MI.
0-24h - cell death & neutrophil recruitment -> lyse dead cells
1-3d - immune response continues breaking cells down
3-14d - macrophages phagocytose debris, granulation tissue begins to form, myocardium fragile
14d-1month - scar tissue, leaving myocardium akinetic
160
What are the short term complications of an MI?
Arrhytmias, muscle rupture, mural thrombus, acute pericarditis
161
What are the long term complications of an MI?
HF, recurrent MI, ventricular aneurysm, Dresslers syndrome (secondary pericarditis)
162
MI risk factors - what specific age, genders and ethnicity indicate higher risk?
Gender - men (>45)
Family history of early CHD (<55-60)
CHD - S Asian
Hypertention & stroke - African-Caribbean
163
What is familial hypercholesterolaemia? How is it diagnosed?
Inherited disease, mutations in 3 genes inc LDLR. Affects 1 in 250-500
Increases CHD risk by 50% (age 50 males)
Diagnosis - Total chol >7.5; LDL >4.9 & family history of premature CHD
164
How do statins work? What are some alternatives, and their effectiveness?
Inhibits cholesterol synthesis in liver (by blocking HMG coA reductase) - 40-60% reduction in LDL-C
Ezetimibe blocks cholesterol absorption in bowel - 15-20% reduction LDL-C
Praulent - stimulates PCSK9 to degranulate LDLR - ?60% reduction
165
How is risk of CHD determined?
QRISK - gives 10y risk
if >10% mortality chance, statins are prescribed
166
What are the main principles of secondary CHD management?
Lower BP & cholesterol (primary prevention too)
Lifestyle:
Cigarette smoking cessation
Dietary change (Red. sat fat, kcal & salt, mediter. diet)
Increase physical activity
Medications:
Statins, Beta blockers, ACEis & antiplatelet (e.g. aspirin)
167
What are the main causes of CHD?
High blood cholesterol (LDL particularly)
High BP (weakens arteries)
Cigarette smoking
Diabetes
Obesity
168
Why does high LDL lead to CVD complications?
Plaques are laden with cholesterol - LDL is the form of chol that transports fat to peripheral tissues
HDL however carries fat to liver for breakdown
