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Phase 1 > CVR🫁💓 > Flashcards

CVR🫁💓 Flashcards

1
Q

What is Gastrulation?

A

Mass movement and invagination of the blastula to form three layers – ectoderm, mesoderm (middle layer) and endoderm

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2
Q

What forms from the ectoderm?

A

Skin, nervous system, neural crest (which contributes to cardiac outflow, coronary arteries)

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3
Q

What does the mesoderm form?

A

All types of muscle, most system, kidneys, blood, bone, cardiovascular system

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4
Q

What does the endoderm form?

A

Gastrointestinal tract (inc liver, pancreas, but not smooth muscle), endocrine organs

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5
Q

What are the two heart fields and what do they give rise to?

A

First heart field - gives rise to early structures
Second heart field - gives rise to more advanced things

FHF – future left ventricle
SHF – outflow tract,
future right ventricle,
atria

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6
Q

List some cardiac transcription factors

A

Nkx2.5, GATA, Hand, Tbx, MEF2, Pitx2, Fog-1

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7
Q

What are the stages of cardiac formation?

A

1.Formation of the primitive heart tube
2.Cardiac looping
3.Cardiac septation

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8
Q

Describe formation of the primitive heart tube

A

In week 3, cells form horseshoe shape called the cardiogenic region. Day 19- 2 endocardial tubes form and fuse on day 21 to form a primitive heart tube.

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9
Q

What is the bulbis cordis?

A

Forms most of the right ventricle and parts of the outflow tracts for the aorta and pulmonary trunk

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10
Q

What does the primitive ventricle become?

A

Most of the left ventricle

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11
Q

What does the primitive atrium become?

A

The anterior parts of the right and left atria

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12
Q

What does the sinus venosus in the left and right horns become?

A

The superior vena cava and part of the right atrium

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13
Q

Describe cardiac looping

A

-Bulbis cordis moves inferiorly, anteriorly and to the embryo’s right
-The primitive ventricle moves to the embryo’s left side
-The primitive atrium and sinus venosus move superiorly and posteriorly
-The sinus venosus is now posterior to the primitive atrium

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14
Q

Describe cardiac septation

A
  • The one atrium and ventricle are connected by the atrioventricular canal
    -Blood exits through the truncus arteriosus
    -Endocardial cushions grow from sides of AV canal to partition into 2 separate openings
    -At the same time the AV canal is being repositioned to the right side of the heart
    -Superior and inferior endocardial cushions fuse to form right and left AV canals
  • Now blood passes through both of them
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15
Q

How does the heart know to have a left orientated ventricle?

A

Cilliary motion at the node pushes the protein nodal towards the left. A cascade of transcription factors (e.g. Lefty, Pitx2, Fog-1) transduce looping

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16
Q

Describe arterial system

A

Conduits of blood; physical properties (elastic arteries) increase efficiency whilst regulatory control (muscular arteries) control distribution

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17
Q

What are Elastic arteries?

A

Major distribution vessels (aorta, brachiocephalic, carotids, subclavian, pulmonary)

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18
Q

What are muscular arteries?

A

Main distributing branches

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19
Q

What are arterioles?

A

Terminal branches (<300mm diameter)

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20
Q

Describe the capillaries

A

The functional part of the circulation
Blood flow regulated by precapillary sphincters
Between 3-40 microns in diameter
Three types of capillary; continuous (most common), fenestrated (kidney, small intestine, endocrine glands), discontinuous (liver sinusoids)

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21
Q

Describe the venous system

A

Return blood to the heart
System of valves allows “muscular pumping”
Some peristaltic movement

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22
Q

What is the innermost layer of the artery/veins?

A

Tunica intima ( endothelium basement membrane)

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23
Q

Second layer of arteries/veins

A

Tunica media (vascular smooth muscle cells)

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24
Q

Third layer of arteries/veins

A

Internal elastic lamina

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25
Q

Fourth layer of arteries/veins

A

Tunica adventitia (fibroblasts)

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26
Q

Outer layer of arteries/veins

A

External elastic lamina

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27
Q

What do you call capillaries that supply blood vessles?

A

Vasa vasorum

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28
Q

What are blood islands and when do they form?

A

Extraembryonic mesoderm
Core of hemoblasts surrounded by
Endothelial cells
Formed on day 17

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29
Q

When does vasculogenesis occur and what is it?

A

Day 18, formation of a central vessel in the latreral mesoderm

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30
Q

What is angiogenesis?

A

Driven by angiogenic growth factors and takes place via proliferation and sprouting
from day 18 onwards other mesodermal cells are recruited to form the structure

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31
Q

What drives embryonic vessel development?

A

Angiogenic growth factors – vascular endothelial growth factor, angiopoietin 1 & 2
Repulsive signals – Plexin / semaphorin signalling, ephrin / Eph interactions
Attractive signals

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32
Q

What do 1st and 2nd aortic arches become?

A

Become minor head vessels
1st – small part of maxillary
2nd - artery to stapedius

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33
Q

What do the 3rd aortic arches become?

A

Portion between 3rd and 4th arch disappears
Become common carotid arteries, and proximal internal carotid arteries
Distal internal carotids come from extension of dorsal aortae

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34
Q

What do the right dorsal aorta and right 4th aortic arch become?

A

R dorsal aorta looses connections with midline aorta and 6th arch, remaining connected to R 4th arch
Acquires branch 7th cervical intersegmental artery, which grows into R upper limb
Right subclavian artery is derived from right 4th arch, right dorsal aorta, and right 7th intersegmental artery

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35
Q

What do the 6th aortic arches become?

A

Right arch may form part of pulmonary trunk
Left arch forms ductus arteriosus – communication between pulmonary artery and aorta

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36
Q

Describe an erythrocyte

A

-2-3 million produced and released from marrow/second
-Lifespan 120 days
-Anucleate biconcave discs
-Haemoglobin to carry oxygen
-Millions of antigens on surface (several hundred are blood group antigens)

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37
Q

What is different about the antigens on red blood cells?

A

They have antigens against the other blood groups even though they have never been in contact with them

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38
Q

What is the antigen that all red blood cells have?

A

H- antigen, this is the only one on blood group O but A and B have an extra sugar chain on it

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39
Q

Describe ABO antibodies

A

-Theorised they develop against environmental antigens
-Infants <3 months produce few if any antibodies (maternal prior to this)
-First true ABO antibodies > 3 months
-Maximal title 5-10 years
-Titre decreases with age
-Mix of IgG and IgM
-IgM mainly for group A and B
-Wide thermal range means they are reactive at 37C

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40
Q

What determines your blood group?

A

The antigens show the blood group that you are. The antibodies are the against the group(s) that you don’t have antigens for. E.g group A has A antigens and B antibodies

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41
Q

What are rhesus antigens

A

-> 45 different Rh antigens
-2 genes, Chromosome 1
-RHD – codes for Rh D
-RHCE – codes for Rh C and Rh E
-Highly immunogenic
Can cause haemolytic transfusion reactions and haemolytic disease of the fetus and newborn (HDFN)

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42
Q

What is the most important rhesus antigen to look at?

A

Rhesus D

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43
Q

When do you have rhesus antibodies?

A

Only when you come into contact with the other rhesus D antigen

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44
Q

What is Haemolytic disease of the fetus/newborn (HDFN)?

A

-Rh D sensitization most common cause
-Develop anti-Rh antibodies
-Severe fetal anaemia
-Hydrops fetalis

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45
Q

How is HDFN prevented?

A

-Detect mothers at risk
-Maternal fetal free DNA
-Anti D prophylaxis

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46
Q

How to test for ABO and Rh D grouping?

A

Forward typing and reverse typing

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47
Q

Describe forward typing

A

-Mix patient’s red blood cells with a solution of either A of B antibodies
-If the blood cells agglutinate, or clump together, it means the sample has reacted with one of the antibodies and so is the opposite blood group

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48
Q

Describe reverse typing

A

-Mix plasma from patient with known red cells and see if they clump together
-Positive is a line at the top of the gel

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49
Q

What is cross matching blood?

A

Units of blood deemed suitable chosen from stocks available:
Either exact match (e.g. A+ for A+) OR
‘Compatible” blood (e.g. O- for A+)
Mix recipient serum with donor RBCS - indirect antiglobulin test

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50
Q

What does the indirect antiglobulin test test for?

A

Blood grouping for ABO and Rhesus D
Detects antibodies in patient’s serum

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51
Q

Describe direct antiglobulin test

A

Detects antibodies on patient’s red cells
? Autoimmune haemolysis
? Transfusion reaction
? Haemolysis due to fetal/maternal group incompatibility

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52
Q

Who can donate blood?

A

-17-65 years old
-Body weight 50-158kg
-Donors screened to highlight those at risk of infectious diseases
-Also screened for health, lifestyle, travel, medical history, medications

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53
Q

Temporary exclusion criteria to donate blood

A

Travel
Tattoos/Body piercings
Lifestyle

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54
Q

Permanent exclusion criteria for donating blood

A

-Certain diseases
-Received blood products or organ/tissue transplant since 1980
-Notified at risk of vCJD

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55
Q

What can you donate?

A

Whole blood
Apheresis

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56
Q

What is Apheresis?

A

Blood removed and externally separated into Plasma, Platelets

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57
Q

Mandatory tests for blood from blood donors

A

Hep B Hep C Hep E
HIV Syphilis
HTLV Groups and antibodies

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58
Q

Describe separation and storage of the blood donated

A

-Whole blood donated into closed system bags
-Blood centrifuged to packed red cells, Buffy coat and plasma
-Plasma only kept from male donors
-Plasma frozen (FFP) or processed to cryoprecipitate
-Red cells passed through leucodepletion filter and suspended in additive
-Buffy coats pooled with matching ABO and D type and then leucodepleted to make platelets

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59
Q

What is a buffy coat and where is it found?

A

The buffy coat is the fraction of an anticoagulated blood sample that contains most of the white blood cells and platelets following centrifugation

Buffy coat is situated in between the plasma and erythrocytes.

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60
Q

What is done with red cells

A

Stored at 4degrees celsius, shelf life 35 days
Some units irradiated to eliminate risk of transfusion-associated graft vs host disease

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61
Q

Indications for needing a rbc transfusion

A

Severe anaemia (not purely iron deficiency)

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62
Q

What is the transfusion threshold?

A

Haemoglobin <70 g/L or <80 g/L + symptoms
Transfuse 1 unit and recheck FBC (unless massive transfusion needed)
Emergency stocks of O Rh D- available in certain hospital areas

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63
Q

Features of platelet donation

A

Most units pooled from 4 donations
Some single-donor apheresis units
Stored at 22oC with constant agitation, 7 day shelf life

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64
Q

Indications for giving platelets

A

Thrombocytopaenia and bleeding
Severe thrombocytopaenia < 10 due to marrow failure (150-450)

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65
Q

Transfusion threshold of platelets (NICE)

A

(all values x10 to the power 9)
<10 if asymptomatic and not bleeding
<30 if minor bleeding
<50 if significant bleeding
<100 if critical site bleeding (brain, eye)
Part of massive transfusion protocol

ABO type still important (units contain ABO antibodies

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66
Q

Describe fresh frozen plasma donation and transfusion protocal

A

From whole donations or apheresis
Patients born > 1996 can only receive plasma from low vCJD risk (not UK plasma)
Single donor packs have variable amounts of clotting factors. Pooled donations can be more standardized

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67
Q

Indications for plasma transfusion

A

Multiple clotting factor deficiencies and bleeding (DIC)
Some single clotting factor deficiencies where no concentrate available

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68
Q

Describe the process of cryoprecipitate transfusion

A

Made by thawing FFP to 4oC and skimming off fibrinogen rich layer
Used in DIC with bleeding, and in massive transfusion
Therapeutic dose: 2 packs (each pooled from 5 plasma donations)

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69
Q

What is immunoglobulin made from?

A

Made from large pools of donor plasma

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70
Q

Describe normal IVIg

A

Contains Ab to viruses common in population
Used to treat immune conditions e.g. ITP

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71
Q

Describe specific IVIg

A

From selected patients
Known high AB levels to particular infections/conditions
Anti D immunoglobulin used in pregnancy
VZV immunoglobulin in severe infection

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72
Q

When/why do you give granulocytes?

A

Used very rarely
Effectiveness controversial
Severely neutropaenic patients with life threatening bacterial infections
Must be irradiated (to kill T cells)

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73
Q

Describe single factor concentrates

A

Factor VIII for severe haemophilia A (recombinant version – no risk of viral or prion transmission)
Fibrinogen concentrate (Factor I)

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74
Q

Describe prothrombin complex concentrate (Beriplex/Octaplex)

A

Multiple factors
Rapid reversal of warfarin

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75
Q

Important things to remember for the safe delivery of blood

A

Patient identification
2 sample rule
Hand-written patient details
Blood selected and serologically cross matched

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76
Q

Common mistakes with blood transfusion

A

Patient identification errors are most common
Wrong blood in wrong tube
Lab errors are much less common
Blood transfusion delayed
Too much blood transfused

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77
Q

How to avoid blood transfusion?

A

Optimise patients with planned surgical procedures pre-op
Use of EPO-stimulating drugs
In renal failure
In patients with cancers
Intraoperative cell salvage
IV iron for severe iron deficiency
Some patients may tolerate lower haemoglobin concentrations and not require transfusion at all

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78
Q

How safe is blood transfusion?

A

Blood transfusion now very safe
Heavily regulated and monitored (SHOT, MHRA)
Potential risk of viral transmission now extremely low
Hep B < 1:1,200,000
Hep C < 1:7,000,000
HIV < 1:28,000,000
Transfusion-related GvHD
Risk reduced by leucodepletion and irradiation
Problems more likely after blood leaves the lab

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79
Q

What happens with ABO incompatability?

A

Rapid intravascular haemolysis
Cytokine release
Acute renal failure and shock
DIC
Can be rapidly fatal

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80
Q

Treatment for haemolytic reactions

A

STOP transfusion immediately
Fluid resuscitate
Send to the lab
Must be reported to SHOT

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81
Q

Describe bacterial contamination of blood products

A

Most commonly with platelets (still v. rare)
Symptoms very soon after transfusion starts
Fever and rigors
Hypotension
Shock
Inspection of unit may show abnormal colouration/cloudiness

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82
Q

What is Transfusion related lung injury?

A

Ab in donor blood reacts with recipient’s pulmonary epithelium/neutrophils
Inflammation causes plasma to leak into alveoli

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83
Q

Symptoms of TRALI

A

SOB
Cough with frothy sputum
Hypotension
Fevers

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84
Q

What is Transfusion related circulatory overload (TACO)?

A

-Acute/worsening pulmonary oedema within 6 hours of transfusion
-Older patients more at risk

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85
Q

Symptoms of TACO

A

Respiratory distress
Evidence of positive fluid balance
Raised blood pressure

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86
Q

How many big squares on an ECG is equal to 1mV?

A

2 big squares

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87
Q

How do you calculate rate from an ECG?

A

Rate (bpm) = 300/no. of large squares between cardiac cycles
or
Rate (bpm) = 300/no. of large squares between cardiac cycles

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88
Q

What does positive deflection mean?

A

Line on ECG goes up
Shows net current flow towards the leas

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89
Q

What is the Baseline (isoelectric point)?

A

No net current flow in direction towards the lead

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90
Q

What is negative deflection?

A

Line on ECG goes down
Net current flow away from the lead

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91
Q

What is the P wave?

A

Depolarisation of the Atria

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92
Q

What is the QRS complex?

A

Ventricular depolarisation

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93
Q

What is the T wave?

A

The repolarisation of the ventricles

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94
Q

What is atrial fibrillation?

A

Random atrial activity
Random ventricular capture
Irregularly irregular rhythm

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95
Q

What is atrial flutter?

A

Organised atrial activity ~300/min
Ventricular capture at ratio to atrial rate (usually 2:1 so 150 bpm)
Usually regular
Can be irregular if ratio varies

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96
Q

What is the normal PR interval length?

A

120-200ms ( 3-5 small squares)

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97
Q

What does an elongated PR interval show?

A

Delayed AV conduction
Heart block

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98
Q

What does a short PR interval show?

A

Wolff-Parkinson-White-Syndrome

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99
Q

What does a longer QRS complex show?

A

QRS>120 ms
Bundle branch block most common cause

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100
Q

What is a QT interval?

A

Measure of time to ventricular repolarization
Time from onset of QRS to end of T

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101
Q

What are the normal values of the QT interval?

A

Men 350-440 ms
Women 350-460 ms

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102
Q

What is an ECG electrode?

A

Physical connection to patient in order to measure potential at that point
10 electrodes to record a 12 lead ECG

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103
Q

What is an ECG lead?

A

Graphical representation of electrical activity in a particular ‘vector’
Calculated by the machine from electrode signals
12 leads for a 12 lead ECG (I-III, aVL, aVF, aVR, V1-6)

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104
Q

What are bipolar leads?

A

Measures the potential difference (voltage) between two electrodes
One electrode designated positive, the other negative

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105
Q

What are Unipolar leads?

A

Measures the potential difference (voltage) between two electrodes
One electrode designated positive, the other negative

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106
Q

What does the right leg electrode do?

A

Neutral electrode
- Reduces artefact – not directly involved in ECG measurement

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107
Q

Describe Lead I

A

Bipolar lead
Designated so that the positive electrode is the left arm and the negative electrode is the right arm
So if current is flowing from right to left then there will be positive deflection
If the other way around then it will be negative deflection
Tells us what is happening in that direction

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108
Q

Describe lead II

A

Right arm is negative electrode and left leg is positive electrode
If current flows towards the left leg then there will be positive deflection
If opposite way around then negative deflection

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109
Q

Describe Lead II

A

Left leg is the positive electrode and the left arm is the negative electrode
If the current flows from the arm to the leg then it is positive deflection, if the other way around then it is negative deflection

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110
Q

What degrees are all of the leads represented as?

A

Lead I- 0
Lead II- +60
Lead III- +120

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111
Q

What is a normal axis?

A

Positive towards leads 1 and 2
In the axis range of -30 to +90

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112
Q

What are AVL, AVF and AVR?

A

Unipolar leads

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113
Q

What axis are the aVL, aVF and aVR leads at?

A

aVL-> -30
aVF-> +90
aVR-> -150

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114
Q

Is the QRS deflection negative or positive for aVR?

A

Negative

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115
Q

What does lead I positive and lead II negative mean?

A

Left axis deviation

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116
Q

What does lead I negative and lead II positive mean?

A

Right axis deviation

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117
Q

What does the right coronary artery supply?

A

Inferior LV wall

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118
Q

What does the left circumflex artery supply?

A

Lateral LV wall

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119
Q

What does the left anterior descending artery supply?

A

Anterior LV wall

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120
Q

In which leads does a problem with the inferior wall show?

A

Lead II, lead III and aVF

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121
Q

What leads are used to see electrical activity in the transverse plane?

A

Chest leads (which are unipolar)
V1-V6

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122
Q

What area of the heart do leads V1 and V2 show electrical activity for?

A

Septal wall

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123
Q

What area of the heart do leads V3 and V4 show electrical activity for?

A

Anterior wall

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124
Q

What area of the heart do leads V5 and V6 supply?

A

Lateral wall

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125
Q

What does ST elevation show?

A

Blocked major coronary artery

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126
Q

Describe the membrane of the heart muscle

A

Normally only permeable to K+
Potential determined only by ions that can cross membrane

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127
Q

Describe negative membrane potential

A

K+ ions diffuse outwards (high to low concentration)
Anions cannot follow
Excess of anions inside the cell
Generates negative potential inside the cell

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128
Q

What are the ion concentrations in the extracellular fluid (mmol/L)?

A

Na+ -> 145
K+ -> 4
Ca2+ -> 2
Cl- -> 120

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129
Q

What are the ion concentrations in the intracellular fluid?

A

Na+ -> 14
K+ -> 135
Ca2+ -> 0.0001
Cl- -> 4

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130
Q

Describe Myocyte membrane pumps

A

K+ pumped IN to cells
Na+ and Ca2+ pumped OUT of cells
Against their electrical and concentration gradients
Therefore requires active transport (Na+-K+ pump)
Requires ATP for energy

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131
Q

Describe phase 4 (resting phase)

A

Sodium forced out by Na/K ATPases. Generates a concentration gradient and therefore a voltage

The setup is now complete, everything from here on relies on passive movement of ions down their gradients.

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132
Q

Describe phase 0 (depolarisation)

A

Large number of Na+ ions enter the cell, causing the charge to increase from -90mv to +20mV = (more) DEPOLARISATION

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133
Q

Describe phase 1 (initial repolarisation)

A

Transient outward current of K+ ions leaving the cell causing a small repolarization

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134
Q

Describe phase 2 (plateau)

A

Calcium channels open, causing calcium to enter the cell and MAINTAIN depolarized state

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135
Q

Describe phase 3 (repolarisation)

A

Outward K+ current causes repolarization back to resting potential

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136
Q

Describe action potential propagation

A

Local depolarization activates nearby Na+ channels

Action potential spreads across membrane

Gap junctions allow cell-to-cell conduction and propagation of action potential through whole myocardium

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137
Q

What does electrical stimulation stimulate the release of to allow for muscle contraction?

A

CALCIUM
Contraction of the heart muscle requires (appropriately-timed) delivery of Ca2+ ions to the cytoplasm
Also known as “Excitation-contraction coupling”

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138
Q

Describe step 1 of Excitation-Contraction coupling

A

Step 1: Calcium influx through surface ion channels

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139
Q

Describe step 2 of Excitation-Contraction coupling

A

Step 2: Amplification of [Ca2+]i with NaCa
Intracellular Calcium concentration
Na Ca = Sodium calcium counter transporter
3 sodium, 1 calcium

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140
Q

Describe step 3 of Excitation-Contraction coupling

A

Step 3: Calcium-induced Calcium Release
CICR
SR = calcium store
Various pumps on surface of the SR maintain this concentration
RyR on surface of SR.
Activated by calcium, causes sustained calcium release

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141
Q

Describe the Troponin-Tropomyosin-Actin-Complex

A

Calcium binds to troponin
Conformational change in tropomyosin reveals myosin binding sites
Myosin head cross-links with actin
Myosin head pivots causing muscle contraction

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142
Q

What are the specialist conduction tissues?

A

SAN
AVN
His / Purkinje system

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143
Q

Describe the ventricle voltage/time graph for the SAN

A

Upsloping Phase 4
Less rapid phase 0
No discernable phase 1 / 2
Upsloping Phase 4
Less rapid phase 0
No discernable phase 1 / 2

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144
Q

Describe the drift of the ventricle voltage/time graph for the SAN

A

Sinus node potential drifts towards threshold
The steeper the drift, the faster the pacemaker

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145
Q

What is the phase 4 slope affected by?

A

Autonomic tone
Drugs
Hypoxia
Electrolytes
Age

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146
Q

What does sympathetic stimulation do?

A

Increases heart rate (positively chronotropic)
Increases force of contraction (positively inotropic)
Increases cardiac output

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147
Q

What does parasympathetic stimulation do?

A

Decreases heart rate (negatively chronotropic)
Decreases force of contraction (negatively inotropic)
Decreases cardiac output

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148
Q

Describe sympathetic control of heart rate

A

Adrenaline and noradrenaline + type 1 beta adrenoreceptors
Increases adenylyl cyclase  increases cAMP

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149
Q

What happens to the heart with increased sympathetic stimulation?

A

Increases heart rate (up to 180-250 bpm)
Increases force of contraction
Large increase in cardiac output (by up to 200%)

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150
Q

What happens to the heart with decreased sympathetic stimulation?

A

Decreases heart rate and force of contraction
Decreases cardiac output (by up to 30%)

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151
Q

What is parasympathetic stimulation of the heartrate controlled by?

A

Acetylcholine
M2 receptors – inhibit adenyl cyclase  reduced cAMP

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152
Q

What happens to the heart with increased parasympathetic stimulation?

A

Decreased heart rate (temporary pause or as low as 30-40 bpm)
Decreased force of contraction
Decreased cardiac output (by up to 50%)

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153
Q

What happens to the heart with decreased parasympathetic stimulation?

A

Increased heart rate

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154
Q

What does the AV node do?

A

Transmits cardiac impulse between atria and ventricles
Delays impulse
Allows atria to empty blood into ventricles
Fewer gap junctions
AV fibres are smaller than atrial fibres
Limits dangerous tachycardias

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155
Q

Describe the conduction of the heart

A

Velocity of conduction
Faster in specialised fibres
Atrial and ventricular muscle fibres: 0.3 to 0.5 m/s
Purkinje Fibers: 4m/s

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156
Q

Describe the His-Purkinje system

A

AV node -> ventricles
Rapid conduction
To allow coordinated ventricular contraction
Very large fibres
High permeability at gap junctions

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157
Q

What is automaticity?

A

Spontaneous discharge rate of heart muscle cells decreases down the heart
SAN (usually) fastest
Ventricular myocardium slowest

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158
Q

Describe the refractory period

A

Resting state= closed -> open via depolarisation

Open -> closed and inactivatable via automatic

Closed and inactivatable -> resting state via repolarisation

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159
Q

Describe the normal refractory period

A

Normal refractory period of ventricle approx 0.25s
Less for atria than for ventricles

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160
Q

Describe the heart muscle during the refractory period

A

Refractory to further stimulation during the action potential
Fast Na+ +/- slow Ca2+ channels closed (inactivating gates)

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161
Q

What does the refractory period do?

A

Prevents excessively frequent contraction
Allows adequate time for heart to fill

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162
Q

What happens after an absolute refractory period?

A

After absolute refractory period
Some Na+ channels still inactivated
K+ channels still open
Only strong stimuli can cause action potentials
Affected by heart rate

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163
Q

What is the importance of platelets in disease?

A

Thrombosis
- Formation of clot (thrombus) inside blood vessel
- Platelets have a central role in arterial thrombosis
Heart attack (myocardial infarction)
Stroke
Sudden death

Antiplatelet medications can be life-saving

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164
Q

What is atherogenesis and atherothrombosis?

A

Atherogenesis- Formation of fatty deposits in the arteries

These fatty deposits then form fibrous plaque and atherosclerotic plaque

Atherothrombosis- the rupture of the fatty deposits and plaque causing a blockage of the artery

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165
Q

Why do we need blood flow control?

A

Maintain blood flow
Maintain arterial pressure
Distribute blood flow
Auto-regulate/homeostasis
Function normally
Prevent catastrophe!
(maladapt in disease)

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166
Q

What are platelets?

A

Fragments of megakaryocytes in bone marrow

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167
Q

Describe platelet shape change

A

Activation -> Shape change
Smooth discoid -> spiculated + pseudopodia
Increases surface area
Increases possibility of cell-cell interactions

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168
Q

What is on the surface of the platelets?

A

Glycoprotein IIb/IIIa (GPIIb/IIIa) receptor (aka integrin aIIbb3)

50,000 to 100,000 copies on resting platelet

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169
Q

Describe platelet activation in terms of the Glycoprotein IIb/IIIa (GPIIb/IIIa) receptor

A

Increases number of receptors
Increases affinity of receptor for fibrinogen
Fibrinogen links receptors, binding platelets together (platelet aggregation)

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170
Q

What happens after atherosclerotic plaque rupture?

A

Platelets adhere to damaged vessel wall
Collagen receptors bind to subendothelial collagen which is exposed by endothelial damage
GPIIb/IIIa also binds to von Willebrand factor (VWF) which is attached to collagen
Soluble agonists are also released and activate platelets

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171
Q

What is shear flow?

A

Blood flow across vessel walls causes shear force

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172
Q

What is Von Willebrand factor?

A

It is a blood glycoprotein that promotes hemostasis (process to prevent bleeding), specifically, platelet adhesion. Initially adheres to endothelial cell, then is rolled until it forms stable adhesion activation

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173
Q

How do platelets get activated?

A

Many different agonists can cause platelet activation incl- collagen, thrombin, thromboxane, ADP
This leads to:
Shape change
Cross-linking of GPIIb/IIIa
Platelet aggregation

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174
Q

What does aspirin do?

A

It inhibits an amplification pathway
Low dose aspirin inhibits COX-1 and high dose aspirin inhibits both COX-1 and COX-2

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175
Q

What does arachidonic acid do?

A

Converted into prostaglandins by COX

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176
Q

What does Cyclooxygenase 1 (COX-1) do?

A

Mediates GI mucosal integrity
Thromboxane A2-mediated platelet aggregation

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177
Q

What does Cyclooxygenase 2 (COX-2) do?

A

Mediates inflammation
Involved in prostacyclin production, which inhibits platelet aggregation and affects renal function

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178
Q

What does ADP do in platelets

A

Platelet purinergic receptors
Platelet P2Y Receptors- P2Y1 and P2Y12
Different G proteins link to different signalling pathways

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179
Q

What does P2Y1 do?

A

Activates phospholipase C
which produces protein kinase C and Ca2+
Initiation of aggregation
Shape change
Causes platelet activation
Results in GPIIb/IIIa fibrinogen cross-linking and aggregation

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180
Q

What does P2Y12 do?

A

Produces P13 kinase and adenylate cyclase
Adenylate cyclase then produces cAMP
Amplification of platelet activation, aggregation and granule release
Sustains platelet activation and aggregation

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181
Q

How is the platelet activation amplified?

A

ADP causes platelet activation via P2Y receptors
Dense granules release ADP, which causes further activation
Activation of GPIIb/IIIa also amplifies platelet activation

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182
Q

How does thrombin affect platelet activation?

A

Thrombin activates protease-activated receptors (PAR) on platelets
This leads to platelet activation and release of ADP, which amplifies this activation

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183
Q

Platelet procoagulant activity mediated by changes to membrane lipid bilayer

A

Platelet activation occurs e.g thrombin activating PAR1
This leads to Ca2+ being released from intracellular stores
This inhibits translocase and activates scramblase which leads to the expression of aminophospholipids on the outer platelet membrane, which allows assembly of prothrombinase complex and generation of thrombin

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184
Q

Describe the mechanisms of platelet activation?

A

Platelet procoagulant activity: activated platelets catalyse thrombin generation, creating an amplification loop that also links with coagulation (the production of fibrin)

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185
Q

Describe a platelet-fibrin clot

A

Fibrin strands that surround red blood cells and platelets

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186
Q

What is the Fibrinolytic system?

A

A dynamic interaction between fibrinolytic and anti-fibrinolytic factors is designed to maintain homeostasis i.e. haemostasis without thrombosis

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187
Q

Mechanism of the fibrinolytic system

A

Endothelium releases tPA which cleaves plasminogen to plasmin - regulated by PAI-1 to form tPA/PAI
Plasmin cleaves fibrin to fibrin degradation products- regulated by antiplasmin to form plasmin: antiplasmin complex

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188
Q

Platelet alpha granules

A

Mediate expression of surface P-selectin and release of inflammatory mediators

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189
Q

Platelets and inflammation

A

Platelets have pro-inflammatory and prothrombotic interactions with leukocytes and release inflammatory mediators from alpha granules

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190
Q

How do monocytes interact with platelets in inflammation?

A

Cytokines e.g. chemotactic molecules
Proteolytic Enzymes
Pro-thrombotic molecules : Tissue factor
Adhesion Molecules e.g. PSGL-1

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191
Q

How do platelets interact with monocytes in inflammation?

A

Inflammatory mediators
Adhesion Molecules e.g. P-Selectin
Coagulation Factors

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192
Q

What drugs are anticoagulants?

A

HEPARINS
FONDAPARINUX
BIVALIRUDIN
RIVAROXABAN
APIXABAN
DABIGATRAN
EDOXABAN

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193
Q

What is aortal-mitro continuity

A

means that endocarditis can spread

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194
Q

Main components of the myocardium

A

Contractile tissue, Connective tissue, fibrous frame, specialised conduction system

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195
Q

What does the pumping action of the heart depend on?

A

The pumping action of the heart depends on interactions between the contractile proteins in its muscular walls.

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196
Q

What does the Cardiac Myocyte do?

A

-The pumping action of the heart depends on interactions between the contractile proteins in its muscular walls.
-The interactions transform the chemical energy derived from ATP into the mechanical work that moves blood under pressure from the great veins into the pulmonary artery, and from the pulmonary veins into the aorta.
-The contractile proteins are activated by a signalling process called excitation-contraction coupling.

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197
Q

When does the excitation-contraction coupling begin and end?

A

Excitation-contraction coupling begins when the action potential depolarizes the cell and ends when ionized calcium (Ca2+) that appears within the cytosol binds to the Ca2+ receptor of the contractile apparatus.

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198
Q

Is movement of Ca2+ passive or active?

A

Movement of Ca2+ into the cytosol is a passive (downhill) process mediated by Ca2+ channels.

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199
Q

When does the heart relax?

A

The heart relaxes when ion exchangers and pumps transport Ca2+ uphill, out of the cytosol.

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200
Q

All or nothing phenomenon

A

Either the heart muscle contracts fully or doesn’t contract at all there is no in between

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201
Q

Key features of the myocyte cell

A

-Filled with cross-striated myofibrils.
-Plasma membrane regulates excitation-contraction coupling and relaxation.
-Plasma membrane separates the cytosol from extra-cellular space and sarcoplasmic reticulum.
-Mitochondria: ATP, aerobic metabolism and oxidative phosphorylation.

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202
Q

Does the relaxation process of the myocardium expend energy?

A

Relaxation process of the heart expends energy just like contraction

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203
Q

What does the heart rely on during aerobic metabolism?

A

Free fatty acids

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204
Q

What does the myocardium rely on for energy during hypoxia?

A

There is no FFA metabolism, thus anaerobic metabolism ensues. This relied on metabolising glucose (anaerobically) producing energy sufficient to maintain the survival of the affected muscle without contraction.

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205
Q

How are contractile proteins arranged?

A

In a regular array of thick and thin filaments (The so called Myofibrils).

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206
Q

What is the A-band?

A

The region of the sarcomere occupied by the thick filaments

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207
Q

What is the I-band?

A

It is occupied only by thin filaments that extend toward the centre of the sarcomere from the Z-lines. It also contains tropomyosin and the troponins.

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208
Q

Where are the Z lines?

A

Z lines bisect each I-band.

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209
Q

Describe the sarcomere

A

-The functional unit of the contractile apparatus,
-The sarcomere is defined as the region between a pair of Z-lines,
-The sarcomere contains two half I-bands and one A-band.

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210
Q

Describe the sarcoplasmic reticulum

A

A membrane network that surrounds the contractile proteins,
The sarcoplasmic reticulum consists of the sarcotubular network at the centre of the sarcomere and the subsarcolemmal cisternae (which abut the T-tubules and the sarcolemma).

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211
Q

What is the transverse tubular system (T-tubule)?

A

Is lined by a membrane that is continuous with the sarcolemma, so that the lumen of the T-tubules carries the extracellular space toward the centre of the myocardial cell.

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212
Q

Describe contraction of the myocardium

A

Sliding of actin over myosin by ATP hydrolysis through the action of ATPase in the head of the myosin molecule.
These heads form the crossbridges that interact with actin, after linkage between calcium and TnC, and deactivation of tropomyosin and TnI.

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213
Q

Describe the features of myosin

A

2 heavy chains, also responsible for the dual heads.
4 light chains.
The heads are perpendicular on the thick filament at rest, and bend towards the centre of the sarcomere during contraction (row.)
alpha myosin and beta myosin.

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214
Q

Describe the features of actin

A

Globular protein.
Double-stranded macromolecular helix (G).
Both form the F actin.

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215
Q

Describe the features of tropomyosin

A

Globular protein.
Double-stranded macromolecular helix (G).
Both form the F actin.

216
Q

What does troponin I do?

A

With tropomyosin inhibit actin and myosin interaction.

217
Q

What does Troponin T do?

A

binds troponin complex to tropomyosin.

218
Q

What does troponin C do?

A

High affinity calcium binding sites, signalling contraction.
Drives TnI away from Actin, allowing its interaction with myosin

219
Q

What is in a contractile unit?

A

Z, I, A and H zones,
Myosin,
Actin,
Tropomyosin,
Troponins,
Titins,
Calcium,
ATP,
Crossbridges.

220
Q

How is the contractile cycle controlled

A

Calcium ions- more means more contraction as more myosin binding sites are exposed
Troponin phosphorylation
Myosin ATPase

221
Q

What are the three basic events in the cardiac cycle?

A
  • LV contraction,
  • LV relaxation,
  • LV filling.
222
Q

What are the steps in LV contraction?

A
  • Isovolumic contraction
  • Maximal ejection
223
Q

What are the steps in LV relaxation?

A
  • Start of relaxation and reduced ejection
  • Isovolumic relaxation
  • Rapid LV filling and LV suction
  • Slow LV filling (diastasis)
  • Atrial booster
224
Q

Describe ventricular contraction (systole)

A

Wave of depolarisation arrives,
Opens the L-calcium tubule, {ECG: Peak of R},
Ca2+ arrive at the contractile proteins,
LVp rises > LAp:
MV closes: M1 of the 1st HS,
LVp rises (isovolumic contraction) > Aop,
AoV opens and Ejection starts.

225
Q

Describe ventricular relaxation (diastole)

A

LVp peaks then decreases.
Influence of phosphorylated phospholambdan, cytosolic calcium is taken up into the SR.
“phase of reduced ejection”.
Ao flow is maintained by aortic distensibility.
LVp < Ao p, Ao. valve closes, A2 of the 2nd HS.
“isovolumic relaxation”, then “MV opens”.

226
Q

Describe ventricular filling

A

LVp < LAp, MV opens, Rapid (E) filling starts.
Ventricular suction (active diastolic relaxation), may also contribute to E filling (esp. ex. ?S3).
Diastasis (separation): LVp=LAp, filling temporarily stops.
Filling is renewed when A contraction (booster), raises LAp creating a pressure gradient.(path, S4)

227
Q

Describe physiologic systole

A
  1. Isovolumic contraction,
  2. Maximal ejection
228
Q

Describe cardiologic systole

A
  1. From M1 to A2,
  2. Only part of isovolumic contraction (includes maximal and reduced ejection phases)
229
Q

Physiologic Diastole

A
  1. Reduced ejection
  2. Isovolumic relaxation
  3. Filling phases
230
Q

Describe cardiologic Diastole

A
  1. A2 to M1 interval (filling phases included)
231
Q

What is preload?

A

The load present before the left ventricular contraction has started

232
Q

What is afterload?

A

Is the load after the ventricle starts to contract

233
Q

What is Starling’s law of the heart?

A

Within physiologic limits, the larger the volume of the heart, the greater the energy of its contraction and the amount of chemical change at each contraction.

234
Q

What is LV filling pressure?

A

Is the difference between LAp and LV diastolic pressure

235
Q

Atrial augmentation

A

Atrial contraction pushes the remainder of the blood at the end of diastole

236
Q

What is the Force-length interaction?

A

The force produced by the skeletal muscle declines when the sarcomere is less than the optimal length (Actin’s projection from Z disc “1m” X 2).
In the cardiac sarcomere, at 80% of the optimal length, only 10% of the maximal force is produced!

237
Q

What is All or none on a cellular level?

A

The cardiac sarcomere must function near the upper limit of their maximal length (LMAX) = 2.2 m.
The physiologic LV volume changes are affected when the sarcomere lengthens from 85% of LMAX to LMAX!
Steep relationship: length-dependent activation.

238
Q

What is the Frank and isovolumic contraction?

A

The heart can, during the cycle, increase and decrease the pressure even if the volume is fixed.
Increasing diastolic heart volume, leads to increased velocity and force of contraction (Frank 1895).
This is the positive inotropic effect.
Ino: Fibre (Greek); tropus: move (Greek).

239
Q

What is contractility?

A

(inotropic state): the state of the heart which enables it to increase its contraction velocity, to achieve higher pressure, when contractility is increased (independent of load)

240
Q

What is elasticity?

A

Is the myocardial ability to recover its normal shape after removal of systolic stress.

241
Q

What is compliance?

A

Is the relationship between the change in stress and the resultant strain.(dP/dV).

242
Q

What is Diastolic distensibility?

A

The pressure required to fill the ventricle to the same diastolic volume.

243
Q

What does the pressure volume loop reflect?

A

contractility in the end-systolic pressure volume relationship

244
Q

When is compliance reflected?

A

At the end diastolic pressure volume relationship

245
Q

Describe the blood flow through the organs

A

Heart 4% Other 3.5%Bronchi 2%Thyroid 1%Adrenal 0.5Heart 4%Other 3.5%Bronchi 2%Thyroid 1%Adrenal 0.5%

246
Q

Where is most of the blood volume?

A

Small veins and venules- 43%
Large systemic veins- 20%
Pulmonary circulation- 12%
Heart- 10%
Systemic arteries- 10%
Capillaries- 5%

247
Q

Important features of the arteries

A

Low resistance conduits
Elastic
Cushion systole
Maintain blood flow to organs during diastole

248
Q

Describe features of arterioles and their function

A

Principal site of resistance to vascular flow
Therefore, TPR = Total Arteriolar Resistance
Determined by local, neural and hormonal factors
Major role in determining arterial pressure
Major role in distributing flow to tissue/organs

249
Q

Describe TPR

A

Basically arteriolar resistance
Vascular smooth muscle (VSM) determines radius
VSM Contracts = ↓Radius = ↑Resistance ↓Flow
VSM Relaxes = ↑Radius = ↓Resistance ↑Flow
Or Vasoconstriction and Vasodilatation
VSM never completely relaxed = myogenic tone
Independent of pressure driving it

250
Q

Describe capillaries

A

40,000km and large area = slow flow
Allows time for nutrient/waste exchange
Plasma or interstitial fluid flow determines the distribution of ECF between these compartments
Flow also determined by
Arteriolar resistance
No. of open pre-capillary sphincters

251
Q

Features of veins

A

Compliant
Low resistance conduits
Capacitance vessels
Up to 70% of blood volume but only 10mmHg
Valves aid venous return (VR) against gravity
Skeletal muscle/Respiratory pump aids return
SNS mediated vasoconstriction maintains VR/VP

252
Q

Describe the lymphatic system

A

Fluid/protein excess filtered from capillaries
Return of this interstitial fluid to CV system
Thoracic duct; left subclavian vein
Uni-directional flow aided

253
Q

What is the lymphatic unidirectional flow aided by?

A

Smooth muscle in lymphatic vessels
Skeletal muscle pump
Respiratory pump

254
Q

Equation for cardiac output

A

Cardiac Output (CO) = Heart Rate (HR) x Stroke Volume (SV)

255
Q

What is the blood pressure equation?

A

Blood pressure = CO x Total Peripheral Resistance (TPR)
(like Ohm’s law: V=IR)

256
Q

What is Ohm’s law?

A

Flow= pressure gradient/resistance

257
Q

What is Poiseuille’s equation?

A

Delta P= 8uLQ/ pi r4

258
Q

What is the equation for pulse pressure?

A

Pulse pressure (PP) = Systolic – Diastolic Pressure

259
Q

What is the equation for mean arterial pressure?

A

Mean Arterial Pressure (MAP)= Diastolic Pressure + 1/3 PP

260
Q

What governs flow?

A

Ohm’s law and Poiseuille’s equation

261
Q

What is Frank-Starling mechanism?

A

How the heart responds to volume
SV increases as End-Diastolic Volume increases
Due to Length-Tension (L-T) relationship of muscle
↑EDV = ↑Stretch = ↑Force of contraction
Cardiac muscle at rest is NOT at its optimum length
↑Venous return = ↑EDV = ↑SV = ↑CO
(even if HR constant)

262
Q

How does stroke volume change in the frank-starling mechanism?

A
263
Q

How does blood volume affect circulation?

A

Venous return important beat to beat (FS mechanism)
Blood volume is an important long term moderator
BV = Na+, H20
Controlling water and sodium conc: Renin-Angiotensin-Aldosterone system; ADH; Adrenals and kidneys

264
Q

What is the goal of control of circulation?

A

Maintain blood flow!
CO = SV x HR

This needs pressure to push blood through peripheral resistance
MAP = CO x TPR

265
Q

What is blood pressure?

A

Pressure of blood within and against the arteries

266
Q

What is systolic pressure?

A

Highest, when ventricles contract (100-150mmHg)

267
Q

What is diastolic blood pressure?

A

Lowest, when ventricles relax (not zero, due to aortic valve and aortic elasticity .. 60-90mmHg)

268
Q

Equation for mean arterial pressure

A

Mean arterial pressure = D + 1/3(S-D)

269
Q

How to measure blood pressure?

A

Measured using a sphygmomanometer
Using brachial artery
Convenient to compress
Level of heart

270
Q

Sounds at each

A

0) > Systolic Pressure = no flow, no sounds-

1) Systolic pressure = high velocity = tap

2-4) Between S and D = thud

5) Diastolic pressure = sounds disappear

271
Q

Components of BP control

A

Autoregulation
Local mediators
Humoral factors
Baroreceptors
Central (neural) control

272
Q

What is Myogenic Autoregulation?

A

Stretch of vascular smooth muscle
Contraction until diameter is normalised or slightly reduced

273
Q

Describe the variation of autoregulation

A

Intrinsic ability of an organ
Constant flow despite perfusion pressure changes

Renal/Cerebral/Coronary = Excellent
Skeletal Muscle/Splanchnic = Moderate
Cutaneous = Poor

274
Q

Brain and heart

A

intrinsic control dominates to maintain BF to vital organs

275
Q

Skin

A

BF is important in general vasoconstrictor response and also in responses to temperature (extrinsic) via hypothalamus

276
Q
A

: dual effects:
at rest, vasoconstrictor (extrinsic) tone is dominant;
upon exercise, intrinsic mechanisms predominate

277
Q

Local humoural factors

A

Vasoconstrictors and vasodilators

278
Q

Vasoconstrictors examples

A

Endothelin-1

Internal Blood Pressure
(myogenic contraction

279
Q

Vasodilators examples

A

Hypoxia
Adenosine
Bradykinin
NO
K+, CO2, H+
Tissue breakdown products

280
Q

How does endothelium control blood pressure

A

Control functions
Essential for control of the circulation

Nitric Oxide (NO) = potent vasodilator
Prostacyclin = potent vasodilator
Endothelin = potent vasoconstrictor

281
Q

Nitric oxide and Prostacyclin

A

The powerful local vasodilators
Produced in endothelium

282
Q

Endothelin

A

Powerful vasoconstrictors

283
Q

Circulating hormonal factors

A

Vasoconstrictors: Epinephrine (skin), Angiotensin II, Vasopressin
Vasodilators: Epinephrine (muscle),
Atrial Natriuretic Peptide

284
Q

What are baroreceptors

A

see slides

285
Q

Arterial baroreceptors

A

Key role in short-term regulation of BP; minute to minute control, response to exercise, haemorrhage

If arterial pressure deviates from ‘norm’ for more than a few days they ‘adapt’/’reset’ to new baseline pressure eg. in hypertension

The major factor in long-term BP control is blood volume (Na+, H20)

286
Q

What are cardiopulmonary barorecteptors

A

Atria, ventricles, PA stretch:

Secretion of ANP
↓vasoconstrictor centre in medulla, ↓ BP;
and ↓release angiotensin, aldosterone & vasopressin (ADH), fluid loss
Blood volume regulation

287
Q

Central neural control loop

A

See slide

288
Q

Describe the main neural influences on the medulla

A

Baroreceptors, Chemoreceptors, Hypothalamus, Cerebral cortex, Skin,
Changes in blood [O2] and [CO2]

289
Q

Other higher centres

A

CV reflexes also require hypothalamus and pons

Stimulation of anterior hypothalamus ↓ BP and HR;
The reverse with posterolateral hypothalamus

Hypothalamus also important in regulation of skin blood flow in response to temperature

290
Q

How does the cerebral cortex affect blood flow and pressure?

A

Stimulation usually ↑ vasoconstriction
Emotion can ↑ vasodilatation and depressor responses eg. blushing, fainting. Effects mediated via medulla but some directly

291
Q

WHat do central chemoreceptors do

A

Chemosensitive regions in medulla
↑PaCO2 = vasoconstriction, ↑peripheral resistance, ↑BP
↓PaCO2 = ↓medullary tonic activity, ↓BP
Similar changes with ↑ and ↓ pH
PaO2 less effect on medulla; Moderate ↓ = vasoconstriction; Severe ↓ = general depression
Effects of PaO2 mainly via peripheral chemoreceptors

292
Q

Short term BP control

A

Baroreceptors
↑BP ⇒ ↑Firing ⇒ ↑PNS/↓SNS ⇒ ↓CO/TPR = ↓BP

293
Q

Long term BP control

A

Volume of blood
Na+, H20, Renin-Angiotensin-Aldosterone and ADH

294
Q

Key central effectors are peripheral

A

Blood vessels (vasodilatation and vasoconstriction: affects TPR)

Heart (rate and contractility:
CO = HR x SV)

Kidney (fluid balance:
longer term control)

295
Q

Homeostasis

A

See slide

296
Q

Physiological relevance of blood pressure

A

Cold
Standing up
Running
Lifting
Injury
Blood loss

297
Q

Pathological relevance of blood pressure

A

Fainting
Orthostatic hypotension
POTS
Heart failure
Hypovolaemic shock
Cardiogenic shock
Heart block
Cushing’s syndrome
Respiratory failure
General anaesthetic

298
Q

Fainting

A

Aetiology = emotion, heat, standing, dehydration
Symptoms = nausea, air hunger, sweating
Physiology = Fall in HR and Venous Pooling (X nerve)
Signs = Collapse due to ↓ CO
HR falls, CO falls, BP falls, perfusion to brain reduced
‘Neuro-cardiogenic syncope’ = Faint!
Treatment = lay supine and elevate limbs to ↑VR
Frank-Starling leads to improved SV and CO
Long term: fluids, salt .. Midodrine (α agonist)
Lifestyle adaptation

299
Q

Blood loss

A

Perfusion to brain must be maintained
Local vasoconstriction
Maintain CO/BP by ↑HR
Sympathetic outflow
Widespread cutaneous vasoconstriction
Eventually .. SHOCK (BP↓, Pulse↑, organ hypoperfusion) and death
Treat: rapid volume replacement EARLY

300
Q

Orthostatic hypotension

A

Aetiology = standing quickly, too long, dehydration, hot room
Symptoms = lightheaded, sweating, syncope
Physiology = Fall in BP and Venous Pooling (X nerve)
Failure to reflexly maintain BP and HR
Perfusion to brain reduced
Treatment = lay supine and elevate limbs to ↑VR
Frank-Starling leads to improved SV and CO
Investigate: Lying/ standing BP; tilt test
Common cause: BP drugs, B blockers, vasodilators
Lifestyle adaptation

301
Q

Postural orthostatic tachycardia syndrome (POTS)

A

Standing
Palpitation, dizzy, near syncope, sweating, debilitating
Physiology = Excess tachycardia response
Investigate = Tilt test
HR↑ >40bpm; BP usually OK
Not well understood

302
Q

Describe the nose

A

Most superior portion of the respiratory tract
Multiple functions
-Temperature of inspired air (0.25 second -contact)
-Humidity (75-80% RH)
-Filter function
-Defence function
Cilia take inhaled particulates backwards to
be swallowed
Splinted open

303
Q

What does the anterior nares open into?

A

The enlarged vestibule
- Skin lined
-Stiff hairs
Surface area of the nose
-Doubled by turbinates

304
Q
A

Superior meatus- under superior turbinate
-Olfactory epithelium
-Cribriform plate
-Sphenoid sinus
Middle meatus- under middle turbinate
-Sinus openings
Inferior meatus- under inferior turbinate
-Nasolacrimal duct
On the lateral nasal wall

305
Q

Describe the paranasal sinuses

A

Pneumatised areas of the;
-Frontal
-Maxillary
-Ethmoid
-Sphenoid bones
Arranged in pairs
Evagination of mucous membrane from the nasal cavity
Extension of the mucosa into the sinus

306
Q

Describe the frontal sinuses

A

Within frontal bone
Midline septum
Over orbit and across superciliary arch
Nerve supply – ophthalmic division of V nerve

307
Q

Describe the maxillary sinuses

A

Located within the body of the maxilla
Pyramidal shape
Open into the middle meatus
Hiatus semilunaris

308
Q

Where is each part of the maxillary sinuses?

A

Base – lateral wall of the nose
Apex – zygomatic process of the maxilla
Roof – floor of the orbit
Floor – alveolar process

309
Q

Describe the ethmoid sinuses

A

Between the eyes
Labyrinth of air cells
Semilunar hiatus of the middle meatus
Nerve supply - ophthalmic and maxillary V nerve (trigeminal nerve)

310
Q

Describe the sphenoid sinuses

A

Medial to the cavernous sinus
Carotid artery, III,IV, V, VI
Inferior to optic canal, dura and pituitary gland
Empties into sphenoethmoidal recess, lateral to the attachment of the nasal septum
Nerve supply – ophthalmic V

311
Q

Describe the pharynx

A

Fibromuscular tube lined with epithelium
Squamous and columnar ciliated, mucous glands
Skull base  C6  Oesophagus
Anterior  Nasal Cavities, mouth and larynx
Nasopharynx
Oropharynx
Laryngopharynx (hypopharynx)

312
Q

Describe the nasopharynx

A

Bounded by
-base of skull
-Sphenoid rostrum
-C Spine
-Posterior nose (choana)
-Inferiorly at soft palate opens to
oropharynx
Eustachian tube orifices (lateral wall)
Supply air to middle ear
Pharyngeal tonsils on posterior wall

313
Q

Soft palate anteriorly
Palatine tonsils on the lateral walls
Palatoglossal folds
Palatopharyngeal folds
Inferiorly to the hyoid bone

A

Soft palate anteriorly
Palatine tonsils on the lateral walls
Palatoglossal folds
Palatopharyngeal folds
Inferiorly to the hyoid bone

314
Q

Describe the larynx

A

Valvular function
Prevents liquids and food from entering lung
Rigid structure
9 cartilages
Multiple muscles
Arytenoid cartilages rotate on the cricoid cartilage to change vocal cords
Vocal cords approximate anteriorly

315
Q

What are the laryngeal cartilages?

A

Single Double
-Epiglottis -Cuneiform
-Thyroid -Corniculate
-Cricoid -Arytenoid

316
Q

Describe laryngeal innervation

A

The vagus (X)
-Superior laryngeal nerve
-Recurrent laryngeal nerve

317
Q

Describe the superior laryngeal nerve

A

-Inferior ganglion
-Lateral pharyngeal wall
-Divides into
-Internal
-Sensation
-External
-Cricothyroid muscle

318
Q

Describe the recurrent laryngeal nerve

A

All muscles except cricothyroid
R and L different
Left
lateral to arch of aorta, loops under aorta, ascends between trachea and oesophagus
Right
R Subclavian artery, plane between trachea and oesophagus

319
Q

Describe the main features of gas exchange

A

20m2 gas exchange area per lung
Minute ventilation approx 5 litres
Cardiac output approx 5 litres per minute
Regional differences in ventilation and perfusion (blood supply)
600 million alveoli

320
Q

lower respiratory structure

A

-Main airways:
Trachea
Main Bronchi
Lobar Bronchi
Segmental branches
Respiratory Bronchiole
Terminal Bronchiole
Alveolar Ducts and Alveoli
-Pleura

321
Q

Angle of Louis

A
322
Q

Describe the trachea

A

Larynx to carina (5th thoracic vertebra, T5)

Oval in cross section
Pseudo stratified, ciliated, columnar epithelium
Goblet cells
Semicircular cartilages
Mobile (3 cm and 1cm, superior and inferior)
Sensory innervation- recurrent laryngeal nerve

323
Q

Describe the bronchi

A

Left and Right main bronchi

Sharp division between these
The carina
R main bronchus more vertically disposed
1-2.5cm long, related to the R pulmonary artery
L main bronchus
5cm long, related to the aortic arch

324
Q

Describe the Lobar bronchi

A

Lobar Bronchi (normal)
-Right
-Upper lobe
-Middle lobe
-Lower lobe
-Left
-Upper lobe and lingular
-Lower lobe

325
Q

What are the left segmental bronchi?

A

Upper lobe: Apico-posterior, Anterior
Lingular: Superior and Inferior
Lower lobe: Apical, Ant, Post, Lat

326
Q

Describe acinus

A

Distal to the terminal bronchiole
Alveoli more profuse with increasing generation of subdivision
Ducts are short tubes with multiple alveoli
Interconnection between alveoli exist (pores of Kohn)

327
Q

Describe the alveoli

A

Type I pneumocytes: Pavement
Type II pneumocytes: Surfactant producers
(keeps alveoli patent)
Alveolar macrophage
Basement membrane
Interstitial tissue
Capillary endothelial cells

328
Q

Describe the pleura of the lungs

A

Visceral: Applied to the lung surface
Parietal: Applied to the internal chest wall
Each a single cell layer
Small amount of fluid between
Continuous with each other at lung root
Parietal pleura has pain sensation
Visceral pleura has only autonomic innervation

329
Q

Describe the blood supply to the lungs

A

Bronchial and pulmonary circulations
Pulmonary circulation
L and R pulmonary arteries run from R ventricle
17 orders of branching
Elastic (>1mm ) and non elastic
Muscular (<1mm )
Arterioles (<0.1mm )
Capillaries

330
Q

How much

A

Requirement to move 5 litres / minute of inspired gas [cardiac output 5 litres / min]

331
Q

What is the respiratory pump?

A

Generation of negative intra-alveolar pressure
Inspiration active requirement to generate flow
Bones, muscles, pleura, peripheral nerves, airways all involved

Bony structures support respiratory muscles and protect lungs
Rib movements; pump handle and water handle

332
Q

What are the muscles of respiration?

A

Inspiration
Largely quiet and due to diaphragm (C3/4/5) contraction
External intercostals (nerve roots at each level)
Expiration
Passive during quiet breathing

333
Q

Describe the pleura

A

2 layers, visceral and parietal
Potential space only between these, few millilitres of fluid

334
Q

Describe the nerves of the respiratory pump

A

-Sensory;
-Sensory receptors assessing flow, stretch
etc..
-C fibres
-Afferent via vagus nerve (10th cranial nerve)
-Autonomic sympathetic, parasympathetic balance

335
Q

What is static lungs

A

Both chest wall and lungs have elastic properties, and a resting (unstressed) volume

Changing this volume requires force
Release of this force leads to a return to the resting volume
Pleural plays an important role linking chest wall and lungs

336
Q

what is needed at the alveoli

A

ventilation and perfusion

337
Q

Ventilation

A

Bulk flow in the airways
allows O2 and CO2 movement
Large surface area required, with minimal distance for gases to move across. Total combined surface area for gas exchange 50-100 m2
300,000,000 alveoli per lung

338
Q

Dead space

A

Volume of air not contributing to ventilation

Anatomic; Approx 150mls
Alveolar; Approx 25mls

Physiological
(Anatomic+Alveolar) = 175mls

339
Q

Describe circulation in the bronchi

A

Blood supply to the lung; branches of the bronchial arteries

Paired branches arising laterally to supply bronchial and peri-bronchial tissue and visceral pleura

Systemic pressures (i.e. LV/aortic pressures)

Venous drainage; bronchial veins draining ultimately into the superior vena cava

340
Q

Describe pulmonary circulation

A

Left and right pulmonary arteries run from right ventricle
Low(er) pressure system (i.e. RV / pulmonary artery pressures)

17 orders of branching
Elastic (>1mm ) and non elastic
Muscular (<1mm )
Arterioles (<0.1mm )
Capillaries

341
Q
A
342
Q

Describe alveolar perfusion

A

1000 capillaries per alveolus
Each erythrocyte may come into contact with multiple alveoli
Erythrocyte thickness an important component of the distance across which gas has to be moved
At rest, 25% the way through capillary, haemoglobin is fully saturated

343
Q

What does alveolar perfusion depend on?

A

Pulmonary artery pressure
Pulmonary venous pressure
Alveolar pressure
Capillaries at the most dependent parts of the lung are preferentially perfused with blood at rest

344
Q

What is hypoxic pulmonary vasoconstriction

A

Matching ventilation and perfusion important
Pulmonary vessels have high capacity for cardiac output
30% of total capacity at rest
Recruiting of alveoli occurs as a consequence of exercise

345
Q

Nomenclature of pulmonary physiology

A

PaCO2- arterial CO2
PACO2- Alveolar CO2
PaO2- arterial O2
PACO2- Alveolar O2
PiO2- Pressure of inspired oxygen

346
Q
A

PaCO2=kVco2/VA
Normally PaCO2= 4-6 KPa

347
Q

Ways that CO2 is carried

A
348
Q

Physiological causes of a high CO2

A
349
Q

Alveolar gas equation

A

PAO2= PiO2-PaCO2/R
R=Respiratory Quotient [ratio of Vol CO2 released/Vol O2 absorbed, assume = 0.8]

350
Q

Causes of low PaO2

A

Alveolar hypoventilation
Reduced PiO2
Ventilation/perfusion mismatching (V/Q)
Diffusion abnormality

351
Q

Describe O2/Hb dissociation curve non linear

A

Sigmoid shape
As each O2 molecule binds, it alters the conformation of haemoglobin, making subsequent binding easier (cooperative binding)
Varying influences
2,3 diphosphoglyceric acid
H+
Temperature
CO2

352
Q

Describe acid base control in the blood

A

Body maintains close control of pH to ensure optimal function (e.g. enzymatic cellular reactions)

Dissolved CO2/carbonic acid/respiratory system interface crucial to the maintenance of this control

pH normally 7.40

H+ concentration 40nmol/l [34-44 nmol/l]

353
Q

Measures you can get from a blood gas

A

PaCO2- arterial CO2
PaO2- arterial O2

354
Q

How does the body control acid/base levels?

A

Blood and tissue buffers important
Carbonic acid / bicarbonate buffer in particular
CO2 under predominant respiratory control (rapid)
HCO3- under predominant renal control (less rapid)

The respiratory system is able to compensate for increased carbonic acid production, but;
Elimination of fixed acids requires a functioning renal system

355
Q

Carbonic acid equilibrium

A

CO2 + H2O <-> H2CO3 <-> H+ + HCO3-
Carbonic anhydrase

356
Q

Henderson-Hasselbalch equation

A

pH=6.1 + log10[[HCO3-]/[0.03*PCO2]]

357
Q

when co2 increases

A

In order to keep pH at 7.4, log of the ratio must equal 1.3
As PaCO2 rises (respiratory failure)
HCO3- must also rise (renal compensatory mechanism) to allow this- as the pH lowers

358
Q

Four main acid base disorders

A

Respiratory acidosis, respiratory alkalosis, metabolic acidosis, metabolic alkalosis

359
Q

Functions of the lung?

A

Respiration:

Ventilation and gas exchange: O2, CO2, pH, warming and humidifying

Non-respiratory functions:

Synthesis, activation and inactivation of vasoactive substances, hormones, neuropeptides
Lung defence: complement activation, leucocyte recruitment, host defence proteins, cytokines and growth factors
Speech, vomiting, defecation.

360
Q

Intrinsic host defences

A

Always present: Physical and chemical. Apoptosis, autophagy, RNA silencing, antiviral proteins

361
Q

Innate defence

A

induced by infection (Interferon, cytokines, macrophages, NK cells)

362
Q

Adaptive immunity

A

Tailored to a pathogen (T cell, B cells)

363
Q

What is epithelium?

A

A tissue composed of cells that line the cavities and surfaces of structures throughout the body. Many glands are also formed from epithelial tissue. It lies on top of connective tissue, and the two layers are separated by a basement membrane.

364
Q

What is respiratory epithelium?

A

serves to moisten and protect the airways. It also functions as a barrier to potential pathogens and foreign particles, preventing infection and tissue injury by action of the mucociliary escalator.

365
Q

Chemical epithelial barriers

A

antiproteinases
anti-fungal peptides
anti-microbial peptides
Antiviral proteins
Opsins

366
Q

Describe mucous and it’s functions

A

Airway mucus is a viscoelastic gel containing water, carbohydrates, proteins, and lipids.

It is the secretory product of the mucous cells (the goblet cells of the airway surface epithelium and the submucosal glands).

Mucus protects the epithelium from foreign material and from fluid loss

Mucus is transported from the lower respiratory tract into the pharynx by air flow and mucociliary clearance.

367
Q

What do cilia do in the lungs?

A

Beat to move mucus up the airways

368
Q

What is a cough and what causes it?

A

A cough is an expulsive reflex that protects the lungs and respiratory passages from foreign bodies
Causes of cough:
1. Irritants- smokes, fumes, dusts ect
2. Diseased conditions like COPD, tumours,ect
3. Infections(influenza)

369
Q

How does a cough happen

A

Defence reflex so afferent and efferent pathways
Afferent

370
Q

What is a sneeze and what causes it?

A

Sneeze is defined as the involuntary expulsion of air containing irritants from the nose
Causes of sneeze:
1. Irritation of nasal mucosa
2. Excess fluid in airway

371
Q

Why can injury to airway epithelium repair its self and how?

A

Injury-> Spreading and dedifferentiation->cell migration->cell proliferation ->redifferentiation -> regeneration

This is because it exhibits a level of functional plasticity

372
Q

What happens when epithelial changes go wrong?

A

We get pulmonary diseases
Underpin many obstructive lung diseases

373
Q

What are mucus plugs/inflammation?

A

Mucus and inflammatory cells blocking airways

374
Q

Key facts about the pulmonary and bronchial circulation

A

Unique dual blood supply of the lungs

Pulmonary Circulation
From Right Ventricle
100% of blood flow

Bronchial Circulation
2% of Left Ventricular Output

375
Q

Describe the pulmonary circulation system

A

Receives 100% of cardiac output (4.5-8L/min.)

Red cell transit time ≈5 seconds.

280 billion capillaries & 300 million alveoli.

Surface area for gas exchange 50 – 100 m2

376
Q

Pulmonary arteries features

A

Vessel wall-> thin
Muscularization-> minor
Need for redistribution-> not in normal state

377
Q

Systemic arteries features

A

Vessel wall-> thick
Muscularization-> significant
Need for redistribution-> yes

378
Q

Pressures of pulmonary circulation (mmHg)

A

RA 5

RV 25/0

PA 25/8

379
Q

Pressures of the systemic circulation

A

LA 5

LV 120/0

Aorta 120/80

380
Q

How do you measure wedge pressure

A
381
Q

What is Ohm’s law?

A

Voltage across circuit = Current x Resistance
V = I R

Pressure across circuit = Cardiac Output x Resistance
mPAP – PAWP = CO x PVR

mPAP (mean pulmonary arterial pressure),
PAWP (pulmonary arterial wedge pressure left atrial pressure),
CO (cardiac output)
PVR (pulmonary vascular resistance)

382
Q

What is pouiseuille’s law?

A

Resistance = (8 x L x viscosity)/(π r4)

A small change in radius can have a big impact on it

383
Q

exercise

A

mPAP – PAWP = CO x PVR

On exercise CO increases significantly but mPAP remains stable/increases slightly
because of recruitment and distention in response to increased pulmonary artery pressure

384
Q

What are the pO2 and pCO2 values for type I and type II respiratory failure?

A

Type I Respiratory Failure
pO2 < 8 kPA
pCO2 <6 kPA

Type II Respiratory Failure
pO2 < 8 kPA
pCO2 >6 kPA

385
Q

Causes of hypoxaemia

A

Hypoventilation
Diffusion Impairment
Shunting
V/Q mismatch

386
Q

What is hypoventilation and what are the causes?

A

Type II Respiratory Failure
pO2 < 8 kPA
pCO2 >6 kPA
Failure to ventilate the alveoli

Causes:
Muscular weakness
Obesity
Loss of respiratory drive

387
Q

Different causes of diffusion of impairment

A

Gaseous Diffusion
Pulmonary Oedema

Blood Diffusion
Anaemia

Membrane Diffusion
Interstitial Fibrosis

388
Q
A
389
Q
A
390
Q

Abbreviations for lung physiology measures

A

TLC- total lung capacity
VC- vital capacity
RV- residual volume
TV- tidal volume
FRC- functional residual capacity

391
Q

Measured values of lung capacity

A

FEV1- Forced expiratory volume in one second
FVC- Forced vital capacity- All the air to residual volume

Flow volume curve
Peak Expiratory Flow (PEF)
Lung volumes
Transfer factor estimates
[Compliance]

392
Q

Forced expiration

A

Most of the air comes out in the first second
Breathe in to total lung capacity (TLC)
Exhale as fast as possible to residual volume (RV)
Volume produced is the vital capacity (FVC)

Volume time graph looks like a sharp increase in the first second then it plateaus

393
Q

Peak flow

A

1/10th of a second in
Can see it on a flow volume graph
Single measure of highest flow during expiration
Peak flow meter, spirometer

Gives reading in litres/minute (L/min)
Very effort dependent
May be measured over time, by giving a patient a PEF meter and chart

394
Q

Flow volume graph for forced expiration

A

Take the exact same procedure
Re-plot the data showing flow as a function of volume
PEF; peak flow
FEF25; flow at point when 25% of total volume to be exhaled has been exhaled
FVC; forced vital capacity

395
Q

What are lung volumes?

A

Expiratory procedures only measure VC, not RV
Various other ways to measure RV and TLC are needed

These include;
Gas dilution
Body box (total body plethysmography; shown in picture)

396
Q

Describe gas dilution

A

Measurement of all air in the lungs that communicates with the airways

Does not measure air in non-communicating bullae

Gas dilution techniques use either closed-circuit helium dilution or open-circuit nitrogen washout

397
Q

Total body/ body box plethysmography

A

Alterative method of measuring lung volume, (Boyle’s law), including gas trapped in bullae.

From the FRC, patient “pants” with an open glottis against a closed shutter to produce changes in the box pressure proportionate to the volume of air in the chest

The volume measured (TGV) represents the lung volume at which the shutter was closed

FRC, inspiratory capacity, expiratory reserve volume, vital capacity all measured

From these volumes and capacities, the residual volume and total lung capacity can be calculated

TLC = VC+RV

398
Q

Transfer estimates

A

Carbon monoxide used to estimate TLCO, as has high affinity for haemoglobin
Single 10 second breath-holding technique
10% helium, 0.3% carbon monoxide, 21% oxygen, remainder nitrogen.

Alveolar sample obtained;
DLCO is calculated from the total volume of the lung, breath-hold time, and the initial and final alveolar concentrations of carbon monoxide.

399
Q

What is TLco an overall measure of the interaction of?

A

alveolar surface area
alveolar capillary perfusion
physical properties of the alveolar capillary interface
capillary volume
haemoglobin concentration, and the reaction rate of carbon monoxide and hemoglobin.

400
Q

Regression equations

A
401
Q

Abnormal FEV1 values

A

Forced expiratory volume in one second in litres
Good overall assessment of lung health

Compare with predicted value
80% or greater “normal”
Above the lower limit of normal for that patient (LLN)
Above mean minus 1.645 SD

402
Q

Abnormal FVC values

A

Compare with predicted value
80% or greater “normal”
Above the lower limit of normal for that patient (LLN)
Above mean minus 1.645 SD

Low value indicates likely Airways Restriction
🫁

403
Q

Abnormal FEV1/ FVC ratio

A

There is a predicted ratio for each individual, but..

Abnormal ratio < 0.70 = airways obstruction

[Can also use the LLN* for each individual patient]
*Lower limit of normal

404
Q

Asthma physiology changes

A

FEV1- Normal or reduced
FVC- Normal
PEF- Typically variable, increased diurnal variation of 20%
MEF- Low, typically ‘scalloped’ shape to the flow volume curve
TLC- High or normal
TLco and Kco- Normal or elevated
eNO- High
RAW- High when airway narrowing present

405
Q

Asthma typical blood gases

A

PaO2 Normal
PaCO2 Low
pH Normal or elevated
HCO3- Normal

406
Q

COPD characteristics

A

COPD is a progressive condition
Typified by wheeze and shortness of breath on exercise, progressively worse with time
Intermittent exacerbations
Typified by airways obstruction and lack of significant PEF variation
Typified by reduced mid expiratory flows
Typified by partial or poor response to treatments

407
Q
A

FEV1- Reduced significantly
FVC- May be normal or reduced
PEF- Typically not variable
MEF- low typical scalloped shaped to the flow volume curve
DLco and Kco- low
eNO- normal
RAW- high

408
Q

COPD typical blood gases

A

PaO2 Low
PaCO2 High in type 2 respiratory failure
Low in type 1 respiratory failure
pH Normal
HCO3- May be elevated if chronic acidosis

409
Q

Asbestosis (pulmonary fibrosis due to asbestos) changes to values

A

FEV1- Reduced significantly
FVC- Reduced significantly
PEF- Typically not variable
MEF- Low or normal
TLC- Reduced
Dlco and Kco- Low
eNO- Normal
RAW- no typical change

410
Q

Asbestosis typical blood gases

A

PaO2 Low
PaCO2 Low
pH Normal
HCO3- Low

411
Q

What is the requirement for respiration?

A

Ensure haemoglobin is as close to full saturation with oxygen as possible
Efficient use of energy resource
Regulate PaCO2 carefully
variations in CO2 and small variations in pH can alter physiological function quite widely

412
Q

Breathing is automatic so…

A

No conscious effort for the basic rhythm
Rate and depth under additional influences
Depends on cyclical excitation and control of many muscles
Upper airway, lower airway, diaphragm, chest wall
Near linear activity
Increase thoracic volume

413
Q

What is taking a breath dependent on?

A

CO2 levels

414
Q

Basic breathing rhythm -Pons

A

Pneumotaxic and Apneustic Centres

415
Q

Basic breathing rhythm in medulla oblongata

A

Phasic discharge of action potentials
Two main groups
Dorsal respiratory group (DRG)
Ventral respiratory group (VRG)

416
Q

When are the DRG and VRG active?

A

DRG; predominantly active during inspiration
VRG; active in both inspiration and expiration

Each are bilateral, and project into the bulbo-spinal motor neuron pools and interconnect

417
Q

Describe the central pattern generator

A

Neural network (interneurons)
Located within DRG/VRG
Precise functional locations not known
Start, stop and resetting of an integrator of background ventilatory drive

418
Q

Describe Inspiration

A

Progressive increase in inspiratory muscle activation
Lungs fill at a constant rate until tidal volume achieved
End of inspiration, rapid decrease in excitation of the respiratory muscles

419
Q

Describe expiration

A

Largely passive due to elastic recoil of thoracic wall
First part of expiration; active slowing with some inspiratory muscle activity
With increased demands, further muscle activity recruited
Expiration can be become active also; with additional abdominal wall muscle activity

420
Q

What is the impact of chemoreceptors in the respiratory system?

A

Central (60% influence from PaCO2) and peripheral (40% influence from PaCO2)

Stimulated by [H+] concentration and gas partial pressures in arterial blood
Brainstem [primary influence is PaCO2]

Carotids and aorta [PaCO2, PaO2 and pH]
Significant interaction

421
Q

What are the central chemoreceptors

A

Located in brainstem
Pontomedullary junction
Not within the DRG/VRG complex

Sensitive to PaCO2 of blood perfusing brain
Blood brain barrier relatively impermeable to H+ and HCO3-
PaCO2 preferentially diffuses into CSF

422
Q

Where are the peripheral chemoreceptors?

A

Carotid bodies
Bifurcation of the common carotid
(IX) cranial nerve afferents
Aortic bodies
Ascending aorta
Vagal (X) nerve afferents

423
Q

What are the peripheral chemoreceptors?

A

Responsible for [all] ventilatory response to hypoxia (reduced PaO2)

Generally not sensitive across normal PaO2 ranges

When exposed to hypoxia, type I cells release stored neurotransmitters that stimulate the cuplike endings of the carotid sinus nerve
Linear response to PaCO2

Interactions between responses

[Poison (e.g. cyanide) and blood pressure responsive]

424
Q

What are the lung receptors and what do they do?

A

Stretch, J and irritant
Afferents; vagus (X)
Combination of slow and fast adapting receptors
Assist with lung volumes and responses to noxious inhaled agents

425
Q

What are stretch lung receptors?

A

Smooth muscle of conducting airways
Sense lung volume, slowly adapting

426
Q

What are irritant lung receptors?

A

Larger conducting airways
Rapidly adapting [cough, gasp]

427
Q

J; juxtapulmonary capillary lung receptors

A

Pulmonary and bronchial C fibres

428
Q

Airway receptors in the nose, nasopharynx and larynx

A

Chemo and mechano receptors
Some appear to sense and monitor flow
Stimulation of these receptors appears to inhibit the central controller

429
Q

Airway receptors in the pharynx

A

Receptors that appear to be activated by swallowing
respiratory activity stops during swallowing protecting against the risk of aspiration of food or liquid

430
Q

Describe muscle proprioceptors

A

Joint, tendon and muscle spindle receptors
Intercostal muscles > > diaphragm
Important roles in perception of breathing effort

431
Q

What happens in ascent

A

Ascending; PiO2 falls (FiO2 remains constant)
Decreased PAO2
Decreased PaO2
Peripheral chemoreceptors fire (e.g carotid)
Activates increased ventilation (VA)
Increased PAO2
Increased PaO2

432
Q

CO2 elimination equation

A

PaCO2=kVco2/ VA

433
Q

How is CO2 carried

A
434
Q

Physiological causes of high CO2

A
435
Q

Causes of low PaO2

A

Alveolar hyperventilation
Reduced PiO2

436
Q

PAO2 normal value

A

20KPa-6KPa/0.8=
20

437
Q

Resp failure blood gases

A

PaO2 <8KPa <60mmHg [10.5 - 13.5]

PaCO2 >6.5KPa >49mmHg
[4.7 – 6.5]

438
Q

Hypoxaemia

A

decrease in pp of oxygen in the blood

439
Q

What is Hypoxia

A

Reduced level of tissue oxygenation

440
Q

Respiratory failure type I

A

PaO2- Low (hypoxaemia)
PaCO2- Low/Normal (hypocapnia/normal)

441
Q
A

PaCO2- low (

442
Q

types of time course for resp failure

A

Acute, rapidly
For example; opiate overdose, trauma, pulmonary embolism

Chronic, over a period of time
For example; COPD, fibrosing lung disease

443
Q

Resp failure type 1 mechanisms

A

Most pulmonary and cardiac causes produce type I failure

Hypoxia
Mismatching of ventilation and perfusion
Shunting
Diffusion impairment
Alveolar hypoventilation

Similar effects on tissues seen with;
Anaemia, carbon monoxide poisoning, methaemoglobinaemia

444
Q

Treatments for resp failure type I

A

Airway patency
Oxygen delivery
Many differing systems
Increasing FiO2

Primary cause (e.g. antibiotics for pneumonia

445
Q

common cause of both type 1 and type 2

A

COPD

446
Q

Respiratory failure; type II mechanisms

A

Lack of respiratory drive
Excess workload
Bellows failure

447
Q

clinical features of hypoxia

A

Central Cyanosis
Oral cavity
May not be obvious in anaemic patients
Irritability
Reduced intellectual function
Reduced consciousness

448
Q

Clinical features of hypercapnia

A

Irritability
Headache
Papilloedema
Warm skin
Bounding pulse
Confusion
Somnolence
Coma

449
Q

Respiratory failure type II treatments

A

Airway patency
Oxygen delivery

Primary cause (e.g. antibiotics for pneumonia)

Treatment with O2 may be more difficult
For example; COPD patients rely on hypoxia to
stimulate respiration

450
Q

How to measure exhaled nitric oxide and what does it show?

A

Simple measure of nitric oxide in exhaled breath
Simple machines able to do this
Measured in ppb
Generally increased in asthma
Not “diagnostic”

A reflection of eosinophilic airway inflammation
High >50ppb, normal <25ppb

451
Q

Asthma and occupation

A

15% of asthma is due to occupation
common causes
High molecular allergens: latex, wood, animals and fish
Low molecular allergens:Glutaraldehyde
Isocyanates
Paints
Metal working fluids
Metals

452
Q

What is the prevalence of asthma?

A

5-16% of people worldwide have asthma
Wide variation between countries

Increase in prevalence second half of the 20th century
Now plateaued mostly

US study; Poorer individuals, African-Americans

Many studies identify a wide range of risk factors

453
Q

How is asthma affected by the environment?

A

Pollens, Infectious agents and microorganisms, Fungi, pets, air pollution
All aggrivate/ cause asthma

454
Q
A

silica, coal grain cotton cadmium

455
Q

What is hypersensitivity pneumonitis?

A

is an inflammation of the alveoli within the lung caused by hypersensitivity to inhaled agents

Acute, sub acute and chronic forms (fibrotic, non fibrotic)
Immune complex related disease
Antigen reacts with antibody
Normally IgG response

Very significant environmental influences; farmers lung, bird fanciers lung, metal working fluids

456
Q

CF genotype classification

A

Class I: no functional CFTR protein is made (e.g. G542X)
Class II: CFTR protein is made but it is mis-folded (e.g. F508del)
Class III: CFTR protein is formed into a channel but it does not open properly (e.g. G551D)
Class IV: CFTR protein is formed into a channel but chloride ions do not cross the channel properly (e.g. R347P)
Class V: CFTR protein is not made in sufficient quantities (e.g. A455E)
Class VI: CFTR protein with decreased cell surface stability (e.g. 120del123)

More than 2000 CF - causing CFTR mutations have been found
Most common of which is F508del [a class II mutation found in up to 80% to 90% of patients]

457
Q

CF prevention management

A

Segregation

Surveillance – frequent review minimum every 3 months

Airway clearance – physio & exercise

Nutrition – pancreatic enzymes, diet high calorie & fat, supplements including vitamins, percutaneous feeding

Psychosocial support

458
Q

CF prevention drugs

A

Suppression of chronic infections – antibiotic nebulisation

Bronchodilation – salbutamol nebulisation

Anti inflammatory – azithromycin, corticosteroids

Diabetes – insulin treatment

Vaccinations – influenza, pneumococcal, SARS CoV 2

459
Q

Describe CF rescue antibiotics

A

2 week course IV antibiotics

Home vs hospital

Issues with frequent antibiotics
Allergies
Renal impairment
Resistance
Access problems
If antibiotics are needed frequently then a port can be put in

460
Q

Genotype directed therapies for cystic fibrosis

A

Small-molecule agents facilitate defective CFTR processing or function
Ivacaftor in G551D (6%) and other specific mutations
Improved lung function (FEV1), BMI, QoL

Orkambi in F508del – only licensed for compassionate use in UK
Mixed outcomes

Gene therapy – further research needed as significant problems with delivery

461
Q

How does Ivacaftor (Kalydeco) work?

A

CFTR potentiator - potentiates chloride secretion via increased CFTR channel opening time

Class III mutations

462
Q

How does lumacaftor (Orkambi) work?

A

Lumacaftor is a CFTR corrector - corrects cellular misprocessing of CFTR (e.g. folding) to facilitate transport from the endoplasmic reticulum

Class II mutation - F508del/F508del

463
Q

Describe some challenges with treating CF

A
  • Adherence to treatment
  • High treatment burden
  • High cost of certain treatments
  • Allergies/intolerances to treatment
  • Different infectious organisms and their resistance to drugs
464
Q

Describe Alpha-1 antitrypsin deficiency (AATD)

A

Autosomal recessive genetic disorder

80 different mutations of SERPINEA1 gene on chromosome 14

Serum antiprotease

M phenotype normal and healthy

S and Z phenotypes major disease associations
Leads to:
Early onset emphysema and bronchiectasis
Unopposed action of neutrophil elastase in the lung

465
Q

Autonomic nervous system

A

The peripheral autonomic nervous system divides into sympathetic and parasympathetic branches, which typically have opposing effects
The autonomic nervous system conveys all outputs from the CNS to the body, except for skeletal muscular control
Two nerves in series, the pre- and post-ganglionic fibres
The parasympathetic ganglia are near their targets with short post-ganglionic nerves, whereas the sympathetic ganglia are near the spinal cord with longer post-ganglionic fibres

466
Q
A
467
Q

Parasympathetic bronchoconstriction

A

Vagus nerve neurons terminate in the parasympathetic ganglia in the airway wall
Short post-synaptic nerve fibres reach the muscle and release acetylcholine (ACh), which acts on muscarinic receptors of the M3 subtype on the muscle cells
This stimulates airway smooth muscle constriction

468
Q

Anti muscularinics

A

Ipratropium bromide (Atrovent) can be used as inhaled treatment to relax airways in asthma and COPD, but is a short acting antimuscarinic (SAMA)

SAMA less widely used since long acting muscarinic antagonists (LAMAs) were developed

Ipratropium is still used in high dose in nebulisers as part of acute management of severe asthma and COPD

469
Q

LAMAs

A

Have long duration of action (many hours), often given once daily (tiotropium)

Increase bronchodilatation and relieve breathlessness in asthma and COPD

Seem to reduce acute attacks (exacerbations) as well

Have other benefits, e.g. on parasympathetic regulation of mucus production

470
Q

Sympathetic regulation of the bronchi

A

Sympathetic NS Regulates the fight-and-flight response

Nerve fibres release noradrenaline which activates adrenergic receptors, of which there are two main types (alpha/beta)

Nerve fibres in humans mainly innervate the blood vessels, but airway smooth muscle cells have adrenergic receptors (beta)

Activation of beta2 receptors on the airway smooth muscle causes muscle relaxation (by activating adenylate cyclase, raising cyclic AMP)

471
Q

What are SABAs and LABAs?

A

Short-acting (salbutamol) and long-acting (formoterol, salmeterol) beta2 agonists are valuable drugs
Given with steroids in asthma, often without steroids in COPD
Often given with LAMA in COPD
Acute rescue of bronchoconstriction
Prevention of bronchoconstriction
Reduction in rates of exacerbations

472
Q

Mechanism of action of Beta 2-agonists

A

Stimulation of β2 adenoreceptors results in activation of adenylate cyclase, increased intracellular cAMP and subsequent airway smooth muscle relaxation

473
Q

Adverse effects of beta2 agonists

A
474
Q

Describe type I hypersensitivity

A

Mediators-> IgE antibodies
Timing-> immediate (within 1 hour)
Examples-> anaphylaxis and hayfever
Antigen interacts with IgE bound to mast cells or basophils
Degranulation of mediators lead to local effects
Histamine the predominant mediator

475
Q

Describe type II hypersensitivity

A

Mediators-> Cytotoxic antibodies bound to cell antigen
Timing-> Hours to days
Examples-> Transfusion reactions Goodpastures (Anti GBM disease)
Antibodies reacting with antigenic determinants on the host cell membrane
Usually IgG or IgM
Outcome depends on whether complement is activated and if metabolism of cell is affected

476
Q

Describe type III hypersensitivity

A

Mediators-> Deposition of immune complexes
Timing-> Typically 7-21 days
Examples-> Hypersensitivity pneumonitis; lupus; post streptococcal Glomerulonephritis

Antigen-immunoglobulin complexes are formed on exposure to the allergen
These are deposited in tissues and cause local activation of complement and neutrophil attraction

477
Q

Describe type IV hypersensitivity

A

Mediators-> T-cells (lymphocytes)
Timing-> Days to weeks or months
Examples-> Tuberculosis; Stevens-Johnson syndrome

T-cell mediated, releasing IL2, IFᵧ and other cytokines
Requires primary sensitisation
Secondary reaction takes 2-3 days to develop
May result from normal immune reaction – if macrophages cannot destroy pathogen, they become giant cells and form granuloma

478
Q

Medical history

A

Age, Gender, Occupation
Presenting complaint
History of presenting complaint
Previous medical condition
Drug history and allergies
Social history- hobbies
Family history+ extended family history
Review of systems

479
Q

Respiratory rate

A

Ususally 10-12 per minute

480
Q

Units of pressure

A

1 bar -1000 millibars
760 mmHg / torr
1 atmosphere absolute (ATA)
10 metres of sea water (msw)
33.08 feet of sea water (fsw)
101.3 kilopascals (kPa)
14psi

481
Q

What is Boyle’s law and what are its applications?

A

At a constant temperature the absolute pressure of a fixed mass of gas is inversely proportional to its volume
P1V1=P2V2

Applications
barotrauma
arterial gas embolism
gas supplies

482
Q

What is the diving reflex?

A

When cold water is splashed on someone’s face then they might have
apnoea
bradycardia
peripheral vasoconstriction

483
Q

What is Dalton’s law?

A

Total pressure exerted by a mixture of gases is equal to the sum of the pressures that would be exerted by each of the gases if it alone were present and occupied the total volume

484
Q

What are the effects of Dalton’s law at sea level and at 10 msw?

A

At sea level;
partial pressure N2 = 0.78 ata, O2 = 0.209 ata

At 10 msw;
partial pressure N2 = 1.56 ata, O2 = 0.418 ata

[Breathing air at 10 msw same PaO2 as breathing 42% O2 at sea level]

485
Q

What is the Lorrain Smith Effect (pulmonary oxygen toxicity)?

A

PiO2 > 0.5 ATA
100% oxygen -> symptoms in 12 - 24 hours
Cough, chest tightness, chest pain, shortness
of breath
Also a problem with ITU patients
Relief with PiO2 < 0.5 ATA
Unit of Pulmonary Toxic Dose (UPTD) can be calculated
Forced Vital Capacity (FVC) can be useful to monitor

486
Q

Describe CNS Oxygen toxicity

A

V - Vision (tunnel vision etc)
E - Ears (tinnitus)
N - Nausea
T - Twitching (extremities or facial muscles)
I - Irritability
D - Dizziness

common final (and often the first) sign will be a convulsion
ConVENTID

487
Q

What is inert gas narcosis?

A

Commonest is nitrogen narcosis
worsens with increasing pressure
first noticed between 30-40 msw
Increased PiN2
individual variation
influencing factors- cold, anxiety, fatigue, drugs, alcohol and some medications
Narcotic potential related to lipid solubility

488
Q

What are the signs and symptoms of inert gas narcosis?

A

10-30m. - Mild impairment of performance
30-50m. - Over confidence, sense of well being
50-70m - Sleepiness, confusion, dizziness
70-90m. - Loss of memory, stupefaction
90+ - Unconsciousness, death

Note: death may occur at much shallower depths

489
Q

What is decompression illness?

A

N2 poorly soluble
Ascent  fall in pressure
 fall in solubilty
 gas bubbles
Type I Cutaneous only
Type II Neurologic
O2, supportive treatments and urgent recompression

490
Q

Describe arterial gas air embolism

A

Gas enters circulation via torn pulmonary veins
Small transpulmonary pressures can lead to AGE
Normally occur within 15 minutes of surfacing

Urgent recompression

491
Q

What is pulmonary barotrauma?

A

Air leaks from burst alveoli:
Pneumothorax
Pneumomediastinum
Subcutaneous emphysema

492
Q

Alveolar gas equation

A

PAO2 = PiO2 – PaCO2/R**

  • One version, not taking into account pH2O
    **R=respiratory quotient, = CO2 produced / O2 consumed

A=Alveolar, a=arterial
R = 0.8 with a normal diet
R approx = 1 with primarily carbohydrate diet
R closer to 0.7 with fat rich diets

493
Q

Normal barometric pressure at different altitudes

A

Barometric pressure Altitude (m)
101 (760) 0
57 (429) 4800
46 (347) see slide 12

494
Q

What is the equation for alveolar arterial O2 difference?

A

Alveolar Arterial O2 difference
Whilst normal pretty complete equilibration of O2, there normally is a small difference between Alveolar and arterial oxygen partial pressure

= PAO2 – PaO2 = (approx) 1KPa

495
Q

Normal blood gases

A

PaO2 10.5 - 13.5 KPa
PaCO2 4.5 - 6.0 KPa
pH 7.36 - 7.44

496
Q

Describe right shift of the oxygen dissociation curve

A

Shifts to the right bc you want to deliver the oxygen to the tissues that are metabolically
active

causes
Acidity
2,3 DPG*
Increased temperature
Increased PCO2

[*2,3 biphosphoglycerate]

497
Q

WHat happens to FiO2 and PiO2 as you ascend?

A

FiO2 remains constant at approx 0.21
PiO2 falls with altitude

498
Q

Describe the response of the lungs at altitude

A

Hypoxia leads to..
Hyperventilation at 10000ft altitude
Increases minute ventilation
Lowers PaCO2
Alkalosis initially
Tachycardia
Adaptive changes
Multiple
Alkalosis compensated by renal bicarbonate excretion

499
Q

What is acute mountain sickness?

A

Recent ascent to over 2500m
Lake Louise score  3
Must have a headache and one other symptom

500
Q

What are the risk factors for acute mountain sickness?

A

Recent travel to over 2500m, after a few hours
Sea level normal dwelling
Altitude, rate of ascent and previous history of AMS
Younger people

Descend; the only reliable treatment [o2, recompress, acetazolamide]
You should never go up higher if you have AMS

501
Q

What increases risk of high altitude pulmonary oedema?

A

Unacclimatised individuals
Cough, shortness of breath
Rapid ascent above 8000ft (2438m)
2-5 days

502
Q

What decre

A

Risk less if sleeping below 6000ft (1829m)
Speed of ascent slower (300-350m/day)
Individual susceptibility
Exercise
Respiratory Tract Infection
Incidence 2% at 4000m

503
Q

What are the treatments of pulmonary oedema

A

O2
Decent urgent
Gamow bag
Steroids
Ca2+ blockers?
Sildenafil

504
Q

What are the main features of High Altitude Cerebral Oedema?

A

Serious
AMS not a pre requisite
Confusion
Behaviour change

505
Q

Treatment for high altitude cerebral oedema?

A

Immediate descent
Symptoms may resolve relatively quickly
Gamow bag

506
Q

What to do at different sea level SaO2s

A

Patients need physiological assessment if they have low O2 levels at sea level

507
Q

Stages of lung development

A

Embryonic 0-5 weeks
Pseudoglandular 5-17 weeks
Cannalicular 16-25 weeks
Alveolar 25 weeks- term

508
Q

Embryonic

A
509
Q

Describe the pseudoglandular phase of lung development

A

5-17 weeks
Exocrine gland only
Major structural units formed.
Angiogenesis
Mucous Glands
Cartilage
Smooth Muscle
Cilia
Lung fluid

510
Q

Describe canalicular phase

A

16-25 weeks.
Distal Architecture
Vascularisation i.e formation of capillary bed
Respiratory bronchioles.
Alveolar ducts.
 Terminal sacs

511
Q

Describe alveolarisation from 25 weeks to birth

A

Alveolar sacs
Type 1 and Type 2 cells
Alveoli simple with thick interstitium

512
Q

Describe alveolarisation from birth to 3-5 years

A

Thinning of alveolar membrane and interstitium
↑ complexity of alveoli

513
Q

5-17

A

Major airways defined
Nests of angiogenesis
Smaller airways down to respiratory bronchioles

514
Q

16-25

A

Terminal bronchioles
Capillary Beds
Alveolar ducts

515
Q

25-40 weeks

A

Alveolar budding, thinning and complexification

516
Q

What goes wrong in the embryonic phase

A

Laryngeal,
Tracheal and oesophageal atresia,tracheal and bronchial stenosis,pulmonary agenesis

517
Q

What goes wrong in the pseudoglandular phase

A

Bronchopulmonary sequestration,cystic adenomatoid malformations, alveolar-capillary dysplasia,

518
Q

Things that go wrong in the alveolar phase

A

Acinar Dysplasia,
alveolar capillary dysplasia,
Pulmonary hyoplasia

519
Q

What are the types of cystic adenomatoid malformations?

A

Type 0- Trachebronchial
Type 1- Bronchial
Type 2- Bronchiolar
Type 3- Alveolar duct
Type 4- Distal acinar

520
Q

Systemic blood vessles

A

Purpose: deliver oxygen to hypoxic tissues
Hypoxia/acidosis/CO2
is vasodilator
Oxygen is vasoconstrictor

521
Q

Pulmonary blood vessles

A

Purpose: pick up oxygen from oxygenated lung
Oxygen is vasodilator
Hypoxia/acidosis is vasoconstrictor

522
Q

Describe the important parts of fetal circulation

A

Lung is not useful organ to fetus
PaO2 = 3.2 kPa (31,000 feet)
Shunting of blood Right Left via ductus arteriosus
High Pulm Vasc Resistance (hypoxia)
Tissue resistance (fluid filled)
Low systemic resistance (placenta)

523
Q

What is in fetal lungs and why?

A

Fetal airways are distended with fluid
Fluid aids in lung development
Actively secreted by lungs

524
Q

Describe the ductus arteriosus

A

Pulmonary trunk linked to the distal arch of aorta by the ductus arteriosus, permitting blood to bypass pulmonary circulation
muscular wall contracts to close after birth (a process mediated by bradykinin)

525
Q

What is the ductus venosus?

A

Oxygenated blood entering the foetus also needs to bypass the primitive liver. This is achieved by passage through the ductus venosus, which is estimated to shunt around 30% of umbilical blood directly to the inferior vena cava

526
Q

Describe the foramen ovale

A

The foramen ovale is a passage between the two atria, which is responsible for bypassing the majority of the circulation

527
Q

What happens to the ductus arteriosus immediately after birth

A
528
Q

Describe the ductus venosus after birth

A
529
Q

WHat happens in the lungs at birth

A

Fluid squeezed out of lungs by birth process
Adrenaline stress leads to increased surfactant release.
Gas inhaled

530
Q

What happens in the blood vessels at birth

A

Oxygen vasodilates pulmonary arteries
Pulmonary vascular resistance falls
Right atrial pressure falls, closing foramen ovale

Umbilical arteries constrict

Ductus arteriosus constricts

531
Q
A

Switch as left side becomes higher pressure than

532
Q

Different types of surfactant

A

Surface active phospholipid
Phosphatidyl choline
Phosphatidyl glycerol
Phosphatidyl inositol
Surfactant proteins A, B, C, D

533
Q

When is surfactant produced and what does it do?

A

Virtual abolition of surface tension
Allows homogeneous aeration
Allows maintenance of functional residual capacity

Produced by Type 2 Pneumocytes from 34 weeks gestation

Dramatic increase in 2 weeks prior to birth

534
Q

What causes a surfactant deficiency?

A

Prematurity
+ Asphyxia
+ Cold
+ Stress
+ Twins

Respiratory Distress Syndrome
Loss of lung volume
Non-compliant lungs
Uneven aeration

535
Q

How to treat surfactant deficiency?

A

Distension of alveoli
Steroids
Adrenaline

536
Q

What is Pulmonary Interstitial Emphysema?

A

Lung cysts rupture and let air out of the ruptured alveoli into the interstitium between the alveoli and capillary

537
Q

Management of pulmonary interstitial emphysema

A

Warmth
Surfactant replacement (if intubated)
Oxygen and fluids
Continuous Positive Airway Pressure (maintain lung volumes, reduce work of breathing)
Positive pressure ventilation if needed

Phase 1 (22 decks)

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