CR2 EOY1S (+ 17 Qs at end) Flashcards
Name 3 sources of endogenous NO [4]
Endogenous NO is derived from:
- Endothelium
- Nerve fibres
- Skeletal Muscle
- Tunica intima
What are the 2 endogenous forms of NOS need to know? [2]
Where are each found? [2]
Are they Ca2+ dependent or independent? [2]
Nitric oxide synthase enzyme (NOS)
NOS type I: neuronal NOS, nNOS
- Found in central & peripheral neuronal cells and muscle
- Calcium dependent
NOS type III: endothelial NOS, eNOS
- Vascular endothelial cells
- Calcium dependent
Decsribe the structure of NOSs xx
NOS: oxidoreductase homodimer enzymes:
- Oxygenase domain: binding for NADPH, FMN & FAD
- Reductase domain: binding for BH4, heme and L’arginine (substrate
- Calmodulin binding site: in between reductase and oxidase domains
What happens to NOS if there is / isn’t BH4 present?
BH4 present: causes dimerisation and proper catalytic activity for NO formation
BH4 absence: causes monomer, becomes a superoxide
For the formation of NO using NOS, what substrates are essential? [3]
Which co-factors are essential? [5]
For the formation of NO using NOS, what substrates are essential? [3]
- L-arginine
- O2
- NADPH
Which co-factors are essential? [5]
- FAD
- FMN
- BH4
- haem
- calmodulin.
OXYGEN is essential for the synthesis. Because of the oxygen requirement, NO synthesis is inhibited in hypoxic tissue
Explain MoA of endothelial NO synthase creating NO
- Normally: eNOS associates with Caveolin 1 in caveolae (invaginations of plasma membrane) this inhibits calmodulin complex (CaM) binding to eNOS
- Shear stress promotes wall stretching, which promotes the dissociation of eNOS from caveolae
- This allows eNOS release into the cytoplasm and its activation (through binding of a Ca2+/ calmodulin (CaM) complex)
- M2-muscarinic acetylcholine receptor activation or other stimulation initiates an influx of Ca2+ that binds to calmodulin.
- eNOS dissociates from Cav1 and then combines to Ca/CaM.
- eNOS is activated leading to synthesis of NO.
[] shear stress favors the activation of eNOS by releasing endothelium-dependent agonists.
What are they? [4]
Increased shear stress favors the activation of eNOS by releasing endothelium-dependent agonists.
Agonists stimulated NO formation:
* Acetylcholine (M3muscarinic)
* Bradykinin
* Substance-P
* Adenosine
Where is nNOS found in the brain? [4]
In brain, nNOS is present in:
- autonomic nitrergic nerves: innervating cerebral arteries and arterioles
- brain neurons
- mature skeletal muscle
- present in on muscle sarcolemma attached to dystrophin
Explain MoA of NO evoking vasodilation
- NO activates guanylate cyclase (GC) in vascular smooth muscle
- This converts guanosine triphosphate to cyclic guanosine monophosphate cGMP
- cGMP acts through cGMP-dependent protein kinases (PKGs) to inactivate myosin.
- The net effect of raised cGMP is to inhibit contraction.
Explain how NO release, during exercise counteracts sympathetic NS xx
During exercise:
- Sympathetic nervous system produces a general vasoconstriction of arterioles in muscle during exercise (mediated by alpha-1 receptors). This tends to reduce local muscle blood flow
BUT
- During exercise the blood flow in active muscles increases over TEN FOLD.
- Due to release of NO AND adenosine and Ca2+ influx (linked to NO formation
Together:
- Vasodilation in active & vasoconstriction in inactive muscles effectively redistributes blood to the active muscles
Whats the craic why NO & fetal lungs when they take their first breath?
Baby takes his or her first breath: the increase in oxygen in the lungs stimulates the synthesis of nitric oxide in the pulmonary endothelium. Causes pulmonary vasodilation
Increased oxygen tension after birth upregulates the expression of eNOS and PKG, which act in concert with the maturational increase in sGC and PKG activities, to contribute to a low postnatal PVR
What causes persistent pulmonary hypertension of the newborn? [1]
- Too little NOS (or inhaled meconium prevents inhaled oxygen reaching the NOS): severe hypoxia
- causes raised pulmonary vascuclar resistance
How does erectile dysfunction occur? [3]
Name a drug class that reverses ED [1]
Endothelial dysfunction leading to smooth muscle cavernosal contraction causes erectile dysfunction (want relaxed cavernosal muscle to allow erection)
cGMP converted back to GTP by proteins known as phosphodiesterases.
Phosphodiesterase (PDE‐5) catalyzes the degradation of cGMP, facilitating smooth muscle contraction
PDE-5 Inhibitors like viagra stop this!
What can endothelial dysfunction be caused by? [4]
Consumptive processes that transform bioavailable NO into other species:
- Reactive oxygen species such as -O2 reacts readily with NO forming peroxynitrite (ONOO−)
- Uncoupling of NOS: BH4 insufficiency results in uncoupled NOS, which produces superoxide anions instead of NO
Deficiencies in production of NO in the endothelium:
- Reduced bioavailability of l-arginine o
- Presence of its inhibitor, asymmetric dimethyl-l-arginine (ADMA)
Name 3 viruses that can cause acute bronchitis [3]
Name 2 bacteria that can cause acute bronchitis [2]
Viruses: Adenovirus, coronavirus, parainfluenza, influenza & rhinovirus
Bacteria: Bordetella pertussis & Mycoplasma pneumonia
Describe the pathophysiology behind acute bronchitis (e.g. caused by respiratory synctial virus)
Epithelial cells: 1st line of defence
RSV: binds and invades mucosal lining via epithelial cells
Epithelial cells switch on immune response after recognised through Toll-like receptor (TLR)-3 and retinoic acid-inducible gene (RIG)-I-like receptors
Cellular infection triggers the release of early inflammatory mediators (e.g.interferons (IFNs) and tumour necrosis factor (TNF)-α) and chemokines (e.g.CXCL8 and CXCL11).
A) Innate: Macrophages and Neutrophils, e.g. PMN polymorphonuclear leukocytes cells recruited PMNs)
B) Acquired: Dendritic cell, triggering B and T cells: CD4, CD8 and primed T cells
How do you distinguish between community acquired pneumonia (CAP) and hospital acquired pneumonia? [1]
Hospital acquired pneumonia is distinguished between CAP by the fact that hospital acquired pneumonia that occurs >48 h after hospital admission & no incubation at time of admission
What is the most frequent causative agent of pneumonia? [1]
What is the second most frequent causative agent of pneumonia? [1]
Streptococcus pneumoniae= 50%
Haemophilus influenzae = 20%
Name the signs of pneumonia [4]
Name a complication that pneuomonia a risk factor for !!
Signs:
- Tachypnoea
- Tachycardia
- Hypoxia
- Hypotension
- Fever
- Confusion
Can lead to sepsis
What investigations would you undertake to ID if Ptx has pneumonia? 6
- CXR: look for consolidation
- PCR to ID pathogen causing infection
- Urea and electrolytes informs severity
- C reactive protein
- FBC
- Liver functon tests
How does CXR compare between acute bronchtits and pneumonia? [1]
Pneumonia: consolidation of the lung parenchyma
Acute bronchitis: appears normal
How do you diagnose community acquired pneumonia (CAP) in:
- Primary care
- Secondary care
Primary care:
- symptoms & new focal chest signs on exam (new complaint less that 7 days old) & at least one systemic feature &or temp greature 38
Secondary care:
- Clinical symptoms & signs of a lower respiratory tract infection + chest-X-ray (consolidation)
How do you assess severity of pneumonia in:
- community
- hospital
Community:CRB65 severity score:
- Confusion
- Resp. rate greater than 30/min
- Blood pressure (SBP <90 or DBP < 60)
- Age <65
Hospital:CRB65 severity score:
- Confusion
- Urea >7
- Resp. rate greater than 30/min
- Blood pressure (SBP <90 or DBP < 60)
- Age <65
Which drugs would you use to manage pneumonia for:
CRB Score 0
CRB Score 1-2
CRB Score 3-4
Always follow yourlocal area guidelines. These are developed by looking at the bacteria in the local area for theirantibiotic resistanceso are specific to that population.
CRB Score 0: Amoxicillin or Doxycycline or Clathromycin
CRB Score 1-2: Amoxicillin AND Clathromycin
OR
Doxycycline
CRB Score 3-4: Benzylpenicillin
What are different methods for O2 delivery systems? [4]
In order of increasing concentrated oxygen therapy:
- Nasal cannuale
- Simple face mask
- Non-rebreather mask
- Venturi mask
How do you diagnose acute bronchitis?
Diagnosis by exclusion:
- Cough >3 weeks
- If signs of consolidation (on CXR), airway obstruction, fever, increase RR, increase HR: NOT acute bronchitis
- If no: is there currently an outbreak of influenza pertusis (whooping cough)?
- If no: Acute bronchitis
How does hypertension damage the heart?
What effect does HTN have on SVR? [1]
State the cardiac remodelling that initially occurs because of HTN [1]
State the effect on heart performance of chronic HTN [2]
HTN leads to increased systemic vascular resistance compared to normal in HTN.
Initially leads to HTN leads toleft ventricular hypertrophy (initially protective, but long term is damaging) to overcome increased afterload:
Chronic HTN leads to diastolic and (eventually) systolic dysfunction: there is less space to in ventricle to pump blood out. This leads to dilated cardiomyopathy/congestive heart failure
what can left ventricular hypertrophy lead to? [3]
Dilated cardiomyopathy/congestive heart failure
If increased cardiac muscle is not well perfused myocardial ischaemia and myocardial infarction can follow.
Conducting system also impacted: increasing risk arrythmias
What are the BP ranges for isolated diastolic HTN (BP)? [1]
Abstract. In various guidelines, isolated diastolic hypertension is defined as diastolic blood pressure >80 or >90mmHg in individuals with normal systolic blood pressure.
Why does obesity increase BP? [3]
- increased oxidative stress damages endothelium of BV: stiffer
- increased RAAS system
- increases sympathetic system
which all influence CVD and CKD, which themselves contribute to BP
When do you start pharmalogical treatment for stage 1 hypertension? [6]
When do you start pharmalogical treatment for stage 2/3 hypertension? [1]
When do you start pharmalogical treatment for stage 1 hypertension?
1 or more of following:
- Target organ damage
- Established cardiovascular disease
- Renal disease
- Diabetes
- Estimated 10‑year risk of cardiovascular disease of 10% or more.
- Use clinical judgement for people with frailty or multimorbidity
When do you start pharmalogical treatment for stage 2/3 hypertension? [1]
- Straight away
What are the main classes of antihypertensives? [5]
ACE inhibitors:
Example: enalapril
Angiotensin-II receptor antagonists:
Example: losartan
Calcium-channel blockers:
Example: amlodipine
Diuretics:
Example: (thiazide-like diuretic) indapamide
Beta-blockers:
Example: metoprolol
Which antihypertensives should not be used for pregnant / breastfeeding women? [2]
ACE inhibitors
AT II receptor antagonists
What is Step One Treatment for HTN?
Offer ACE inhibitor or Angiotensin receptor blockers (ARBs) if have:
- type 2 diabetes
- under 55 but not black African / African-Caribbean
OR
Offer calcium-channel blocker (CCB) who:
- aged 55 or over AND no type 2 diabetes
- black African / African-Caribbean
What is Step Two Treatment for HTN?
- If already on ACE inhibitor? [2]
- If already on CCB? [3]
If on ACE inhibitor:
- Add CCB or thiazide-like diuretic [2]
If on CCB:
- Add ACE inhibitor or ARB or thiazide-like diuretic
What is Step Three Treatment for HTN? [3]
ACE inhibitor or ARB & CCB & Thiazide-like diuretic
What specifically about obesity causes increase in HTN? [1]
High leptin levels increase activity of RAAS and sympathetic NS
Which of the following is a not a source of endogenous NO?
- Endothelium
- Nerve fibres
- Connective Tissue
- Skeletal Muscle
- Tunica intima
Which of the following is a not a source of endogenous NO?
- Endothelium
- Nerve fibres
- Connective Tissue - Skeletal Muscle
- Tunica intima
Which of the following is not a substrate used in the formation of NO using NOS
- L-arginine
- BH4
- O2
- NADPH
Which of the following is not a substrate used in the formation of NO using NOS
- L-arginine
- BH4: co factor - O2
- NADPH
What is the threshold for an urea score contributing to CURB65 score?
> 4
5
6
7
8
What is the threshold for an urea score contributing to CURB65 score?
> 4
5
6
>7
8
When you see someone out of hospital with a CRB-65 score of anything other than [] NICE suggest considering referring to the hospital.
0
1
2
3
4
When you see someone out of hospital with a CRB-65 score of anything other than [] NICE suggest considering referring to the hospital.
0
1
2
3
4
What are the two most common causes of left ventricular hypertrophy? [2]
Aortic Stenosis
HTN
An [] is the test of choice in establishing the diagnosis of LVH
ECG
Echocardiogram
Doppler
Cardiac ultrasound
MRI
An [] is the test of choice in establishing the diagnosis of LVH
ECG
Echocardiogram
Doppler
Cardiac ultrasound
MRI
Anti-hypertensives:
Which of the following class of drug does indapamide fall into?
ACE inhibitors:
Angiotensin-II receptor antagonists
Calcium-channel blocker
Diuretics
Beta-blockers
Which of the following class of drug does indapamide fall into?
ACE inhibitors:
Angiotensin-II receptor antagonists
Calcium-channel blocker
Diuretics thiazide-like diuretic
Beta-blockers
Which of the following class of drug does metoprolol fall into?
ACE inhibitors:
Angiotensin-II receptor antagonists
Calcium-channel blocker
Diuretics
Beta-blockers
Which of the following class of drug does metoprolol fall into?
ACE inhibitors:
Angiotensin-II receptor antagonists
Calcium-channel blocker
Diuretics
Beta-blockers
Which of the following class of drug does amlodipine fall into?
ACE inhibitors:
Angiotensin-II receptor antagonists
Calcium-channel blocker
Diuretics
Beta-blockers
Which of the following class of drug does amlodipine fall into?
ACE inhibitors:
Angiotensin-II receptor antagonists
Calcium-channel blocker
Diuretics
Beta-blockers
Which of the following class of drug does enalapril fall into?
ACE inhibitors:
Angiotensin-II receptor antagonists
Calcium-channel blocker
Diuretics
Beta-blockers
Which of the following class of drug does enalapril fall into?
ACE inhibitors:
Angiotensin-II receptor antagonists
Calcium-channel blocker
Diuretics
Beta-blockers
Which of the following class of drug does losartan fall into?
ACE inhibitors:
Angiotensin-II receptor antagonists
Calcium-channel blocker
Diuretics
Beta-blockers
Which of the following class of drug does losartan fall into?
ACE inhibitors:
Angiotensin-II receptor antagonists
Calcium-channel blocker
Diuretics
Beta-blockers
Which of the following would you use to deliver 24 – 30% O2 (maximum flow rate of 4L/min) for mild hypoxia?
Nasal cannulae
Simple face mask
Non-rebreather mask
Venturi mask
Which of the following would you use to deliver 24 – 30% O2 (maximum flow rate of 4L/min) for mild hypoxia?
Nasal cannulae
Simple face mask
Non-rebreather mask
Venturi mask
Which of the following would you use to deliver for patients with chronic obstructive pulmonary disease (COPD) due to the risk of type 2 respiratory failure.
Nasal cannulae
Simple face mask
Non-rebreather mask
Venturi mask
Which of the following would you use to deliver for patients with chronic obstructive pulmonary disease (COPD) due to the risk of type 2 respiratory failure.
Nasal cannulae
Simple face mask
Non-rebreather mask
Venturi mask
Which of the following would you use to deliver approximately 70% O2 when used with a 15L oxygen flow rate.
Nasal cannulae
Simple face mask
Non-rebreather mask
Venturi mask
Which of the following would you use to deliver approximately 70% O2 when used with a 15L oxygen flow rate.
Nasal cannulae
Simple face mask
Non-rebreather mask
Venturi mask
7Which of the following would you use to deliver 30 – 40% O2 (flow rate 5-10 L/min)
Nasal cannulae
Simple face mask
Non-rebreather mask
Venturi mask
Which of the following would you use to deliver 30 – 40% O2 (flow rate 5-10 L/min)
Nasal cannulae
Simple face mask
Non-rebreather mask
Venturi mask
Which of the following would used to treat patients with a significant degree of hypoxia (moderate to severe).
Nasal cannulae
Simple face mask
Non-rebreather mask
Venturi mask
Which of the following would used to treat patients with a significant degree of hypoxia (moderate to severe).
Nasal cannulae
Simple face mask
Non-rebreather mask
Venturi mask
