Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

CR2 > CR Revision 8 > Flashcards

CR Revision 8 Flashcards

1
Q

Name 3 sources of endogenous NO [4]

A

Endogenous NO is derived from:
- Endothelium
- Nerve fibres
- Skeletal Muscle
- Tunica intima

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the 2 endogenous forms of NOS need to know? [2]

Where are each found? [2]

Are they Ca2+ dependent or independent? [2]

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Decsribe the structure of NOSs xx

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What happens to NOS if there is / isn’t BH4 present?

A

BH4 prescene: causes dimerisation and proper catalytic activity for NO formation

BH4 absence: causes monomer, becomes a superoxide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

For the formation of NO using NOS, what substrates are essential? [3]

Which co-factors are essential? [5]

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Explain MoA of endothelial NO synthase creating NO

A
  • 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.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

[] shear stress favors the activation of eNOS by releasing endothelium-dependent agonists.

What are they? [4]

A

Increased shear stress favors the activation of eNOS by releasing endothelium-dependent agonists.

Agonists stimulated NO formation:
* Acetylcholine (M3muscarinic)
* Bradykinin
* Substance-P
* Adenosine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Where is nNOS found in the brain? [4]

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Explain MoA of NO evoking vasodilation

A
  • 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.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Explain how NO release, during exercise counteracts sympathetic NS xx

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Why does muscular dystrophy occur?

A

In dystrophic muscle:

  • nNO is reduce, less NO is generated during muscle contraction, resulting in unrestrained sympathetic vasoconstriction and transient functional muscle ischemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Why does muscular dystrophy occur?

A

In dystrophic muscle:

  • nNO is reduce, less NO is generated during muscle contraction, resulting in unrestrained sympathetic vasoconstriction and transient functional muscle ischemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Whats the craic why NO & fetal lungs when they take their first breath?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What causes persistent pulmonary hypertension of the newborn? [1]

A
  • Too little NOS (or inhaled meconium prevents inhaled oxygen reaching the NOS): severe hypoxia
  • causes raised pulmonary vascuclar resistance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How does erectile dysfunction occur? [3]

Name a drug class that reverses ED [1]

A

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!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is endothelial dysfunction?

A

Pathological state of the endothelium characterized by a reduction in the bioavailability of vasodilators, essentially nitric oxide.

Endothelium becomes prothrombotic and proinflammatory

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What can endothelial dysfunction be caused by? [4]

A

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 ofl-arginine o
- Presence of its inhibitor, asymmetric dimethyl-l-arginine (ADMA)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Endothelial dysfunction leads to vascular and metabolic disorders such as WHAT? [6]

A

Hypertension, hyperlipidemia, atherosclerosis, insulin resistance, and diabetes mellitus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Name 3 viruses that can cause acute bronchitis [3]
Name 2 bacteria that can cause acute bronchitis [2]

A

Viruses: Adenovirus, coronavirus, parainfluenza, influenza & rhinovirus
Bacteria: Bordetella pertussis & Mycoplasma pneumonia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Describe the pathophysiology behind acute bronchitis (e.g. caused by respiratory synctial virus)

A

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 well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How do you distinguish between community acquired pneumonia (CAP) and hospital acquired pneumonia? [1]

A

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

22
Q

What is the definition of pneumonia? [1]

Which populations are most at risk of pneumonia? [1]

A

Pneumonia: inflammation of the alveoli in either one or both lungs: Alveoli become inflamed & fill up with sputum.

V. young and elderly are most at risk

23
Q

What is the most frequent causative agent of pneumonia? [1]

What is the second most frequent causative agent of pneumonia? [1]

A

Streptococcus pneumoniae= 50%

Haemophilus influenzae = 20%

24
Q

Describe the symptoms of pneumonia [4]

How long do pneumonia symptoms normally last? [1]

How long are daily activities normally impaired for? [1]

A
  • headache
  • fever
  • weakness
  • dry cough
  • nasal congestion
  • chills
  • sweating
  • muscle aches

Duration: 3-4 weeks

Impairment: Further 3 weeks

25
Q

Name the signs of pneumonia [4]

Name a complication that pneuomonia a risk factor for !!

A

Signs:
- Tachypnoea
- Tachycardia
- Hypoxia
- Hypotension
- Fever
- Confusion

Can lead to sepsis

26
Q

What investigations would you undertake to ID if Ptx has pneumonia? 6

A
  • CXR: look for consolidation
  • PCR to ID pathogen causing infection
  • Urea and electrolytes informs severity
  • C reactive protein
  • FBC
  • Liver functon tests
27
Q

How does CXR compare between acute bronchtits and pneumonia? [1]

A

Pneumonia: consolidation of the lung parenchyma

Acute bronchitis: appears normal

28
Q

How do you diagnose community acquired pneumonia (CAP) in:

  • Primary care
  • Secondary care
A

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)

29
Q

How do you assess severity of pneumonia in:

  • community
  • hospital
A

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

30
Q

Which drugs would you use to manage pneumonia for:

CRB Score 0
CRB Score 1-2
CRB Score 3-4

A

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

31
Q

What are different methods for O2 delivery systems? [4]

A

In order of increasing concentrated oxygen therapy:

  • Nasal cannuale
  • Simple face mask
  • Non-rebreather mask
  • Venturi mask
32
Q

Why may doxycycline be preferred to amoxycillin as first line of treatment? [1]

A

Doxy has greater broad spectrum antibiotic than amoxy

33
Q

How do you diagnose acute bronchitis?

A

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
34
Q

How do you treat acute bronchitis?

A

Self limiting: establish expectation of cough of 14 days

Encourage fluid intake. Explain lack of antiobiotic evidence

Recommend analgesics like paracetemol

35
Q

Which organ is most directly effected by high BP?

Lungs
Heart
Kidneys
Eyes
Brain
A

Which organ is most directly effected by high BP?

Lungs
Heart
Kidneys
Eyes
**​Brain**
36
Q

Name 5 consequences of hypertension [5]

A

Hypertension:

**Left ventricular hypertrophy
Myocardial infarction
Dilated cardiomyopathy
Stroke** (haemorrhagic & ischaemic)
**Hypertensive kidney disease**
37
Q

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]

A

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

38
Q

what can left ventricular hypertrophy lead to? [3]

A

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

39
Q

HTN increases risk CVA in which three ways? [3]

A

Large and medium vessel atherosclerosis: stress on arteries causes endothelial damage and atherosclerosis

Lipohyalinosis: accumulation of lipids and decreased luminal diameter – increased risk rupturing and bleeding. Causes lacunar infarcts –> damage to middle cerebral arteries​

Cardio-embolic stroke: Increases risk for atrial fibrillation (which increases clots) by causing increased afterload and atrial dilatation.

40
Q

What are the BP ranges for isolated diastolic HTN (BP)? [1]

A

Abstract. In various guidelines, isolated diastolic hypertension is defined as diastolic blood pressure >80 or >90mmHg in individuals with normal systolic blood pressure.

41
Q

What is the difference between primary and secondary hypertension? [1]

Name 4 causes of 2ry HTN [4]

A

Primary HTN: no obvious direct underlying pathological cause; Strong polygenic familial trend. 90-95%

  • *Secondary HTN:** clear underlying causes:
  • Renal or renovascular disease
  • Endocrine disease
  • Coarctation of the aorta
  • Iatrogenic (induced inadvertently by medical treatment or diagnostic procedures). eg. NSAIDs / hormones
42
Q

Which factors, controlled by genes, influences increased BP? [4]
Which non-modfiable factors influences BP? [4]
Which modifiable factors influence BP? [6]

A
  • *Gene controlled:**
  • sodium channels
  • Angiotensinogen
  • Aldosterone
  • ANP & BNP
  • *Non modiafiable:**
  • Age
  • Sex (male)
  • Black ancestry
  • FHx
  • *Modiafiable**:
  • Weight
  • Activity
  • Salt
  • Stress
  • Alchohol
  • Smoking
43
Q

Why does obesity increase BP? [3]

A
  • 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

44
Q

When do you start pharmalogical treatment for stage 1 hypertension? [6]

When do you start pharmalogical treatment for stage 2/3 hypertension? [1]

A

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

45
Q

What are the main classes of antihypertensives? [5]

A

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

46
Q

Which antihypertensives should not be used for pregnant / breastfeeding women? [2]

A

ACE inhibitors
AT II receptor antagonists

47
Q

What is Step One Treatment for HTN?

A

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
48
Q

What is Step Two Treatment for HTN?

  • If already on ACE inhibitor? [2]
  • If already on CCB? [3]
A

If on ACE inhibitor:
- Add CCB or thiazide-like diuretic [2]

If on CCB:
- Add ACE inhibitor or ARB or thiazide-like diuretic

49
Q

What is Step Three Treatment for HTN? [3]

A 
ACE inhibitor or ARB 
&
CCB
&
Thiazide-like diuretic
50
Q

What is step 4 treatment?

A

If hypertension is not controlled in adults taking optimal tolerated doses of an ACE inhibitor or an ARB plus a CCB and a thiazide-like diuretic, regard them as having resistant hypertension.

Before considering further treatment for a person with resistant hypertension:

Confirm elevated clinic blood pressure measurements using ambulatory or home blood pressure recordings.

For people with confirmed resistant hypertension, consider adding a fourth antihypertensive drug as step 4 treatment or seeking specialist advice.

51
Q

What specifically about obesity causes increase in HTN? [1]

A

High leptin levels increase activity of RAAS and sympathetic NS

52
Q

Long term HTN can lead to which pathologies? [3]

A
  • If increased cardiac muscle is not well perfused myocardial ischaemia and myocardial infarction can follow.
  • Conducting system also impacted –increasing risk arrythmias

CR2 (59 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions