PHSL 232 - LECTURE 23

describe the resistance in pulmonary circulation

• low resistance due to large diameter vessels and large cross-sectional area

describe the flow in pulmonary circulation compared to systemic circulation

• same

• recieves the same cardiac output

• 5L/min

describe the compliance of vessels in pulmonary circulation

• high compliance due to thin distensible vessels

describe the pressure in pulmonary circulation

low pressure

why does pulmonary hypertension often go unnoticed

• because measuring pulmonary artery pressure is an extremely invasive process

what is pulmonary hypertension defined us

• mean arterial blood pressure above 25 mmHg

what is pulmonary hypertension associated with

• arterial stiffening

• vasoconstriciton

• impaired gas exchange

what are some symptoms of pulmonary hypertension

• dyspnea

• dizziness

• fatigue

• peripheral edema

what is dyspnea

• shortness of breath which comes down to impaired gas exchange - its going to feel like theyre not getting enough oxygen

can pulmonary hypertension be treated

• no only management

what layers of the arterial wall does the pulmonary hypertension affect

• intima or media

describe the remodelling that is seen in the intima with pulmonary hypertension

• thickening

• endothelial dysfunction - lack of NO

• proliferation (different to systemic hypertension)

• apoptopic resistant

• fibrosis due to fibroblast activation

describe the remodelling that is seen in the media with pulmonary hypertension

• muscularisation and thickening

• VMSCs proliferate

• hypertrophy

what pathophysiology do we see with late stage pulmonary hypertension

• plexiform lesions

• microvascular degeneration

what is a plexiform lesion

• upregulation in vascular endothelial growth factor which causes angiogenesis, creating a plexus of blood vessels with no real purpose.

• The network of capillaries will block or occlude the lumen completely.

• The plexus can also be kinda aneurysm like (aneurysm is bursting blood vessel)

what is the leading cause of pulmonary hypertension

congestive heart failure

what is congestive heart failure

late stage left heart failure - systolic heart failure

heart failure due to fluid build up - congestion

describe the mechanism behind congestive heart failure

• dilated chamber and weakened walls leads to decreased cardiac output from the left ventricle

• the decresed cardiac output leads to decreased blood pressure

• this is detected by the kidneys which activates RAAS system

• the RAAS system leads to fluid retention, which restores the MABP

• Now the body has extra fluid volume, but the left ventricle is still dilated, weak, and stiff from fibrosis (impaired relaxation)

• blood cannot be pumped out effectively, end systolic volume increased

• left ventricle becomes engorged, increasing left ventricular filling pressure.

• left ventricle is full and under high pressure

• blood coming from the lungs via the pulmonary veins has nowhere to go

• The pressure backs up (retrograde) from the left heart into the pulmonary veins, and then into the pulmonary capillaries.

• retrograde backup causes a massive increase in capillary hydrostatic pressure in the lungs.

• Fluid is forced out of the capillaries and accumulates in the lung tissue (pulmonary edema) - congestion

how does congestive heart failure cause pulmonary hypertension

• Because the pressure in the pulmonary capillaries and veins is now abnormally high the pulmonary artery has to drive its own pressure even higher just to force blood through the lungs and into the left heart

• This directly results in post-capillary pulmonary hypertension.

what is chronic obstructive pulmonary disease

• inflammatory condition stimulated by inhaling toxic particles and gases

what is COPD characterised by

• chronic airway inflammation - bronchitis

• mucous production

• lung tissue remodelling - fibrosis

• collapse of small airways

• alveolar wall destruction

what do the symptoms of COPD lead to

• hypoventilation whcih leads to low alveolar oxygen > hypoxemia

• this leads to hypoxic pulmonary vasoconstriction near poorly ventilated alveoli - to divert blood else where

• this overall increases pulmonary vascular resistance

• therefore we get incerased pulmonary arterial pressure> pre-capillary hypertension

what causes pre-capillary hypertension

• moderate to severe cases of chronic obstructive pulmonary disease

what are the consequences of the pre-capillary hypertension on the pulmonary system

• right heart remodelling

• small airway disease

• hypoxemia

• increased pulmonary capillary hydrostatic pressure

how does pre-capillary hypertension cause small airway disease

• the inflammatory factors that were initially acting on the vessels go off and begin acting on the bronchi - shared inflammatory pathways

• they get damaged (fibrosis) and start narrowing

how does pre-capillary hypertension cause increased pulmonary capillary hydrostatic pressure

The increased pressure forces fluid out of the capillaries and into the interstitial space of the lung tissue

• This fluid build-up increases the physical diffusion distance for gases, drastically reducing oxygen exchange capacity and leading to dangerously low blood oxygen levels (hypoxemia).

which side of the heart does hypertension more aggressively impact

the right side

why does the pulmonary system see more aggressive changes in pressure that the systemic system in hypertension

• in the systemic system, the aorta accounts for 80% of the compliance while the resistance is controlled downstream by many arterioles

• and so stiffening of the arteries mostly affects the systolic pressure, and not so much the diastolic

• in the pulmonary circulation, the resistance and the pressure is more evenly distributed throughout the whole system, and so both the systolic and diastolic pressure are heavily affected

why does the right side of the heart see a greater change due to high afterload compared to the left side of the heart

• the left heart is often exposed to changes in resistance/afterload because it is often exposed to high demand in exercise and stressful environments and so it has a higher capacity to handle changes in systemic pressure

• the right heart is sensitive to changes in afterload, and so even a small change can have a drastic effect and remodels to a greater extent

describe the early stage remodelling of the right heart

• compensatory concentric right ventricle hypertrophy

describe compensatory concentric right ventricle hypertrophy

• more sarcomeres added in parallel, wall thickens

describe late stage right heart remodelling

• decompensated eccentric right ventricle hypertrophy

describe decompensated eccentric right ventricle hypertrophy

• ventricle is burnt out

• myocardial ischaemia leads to weak right ventricle wall

• end systolic volume increases

• volume overload leads to chamber dilation (eccentric hypertrophy, sarcomeres added in series)

what does decompensated eccentric right ventricle hypertrophy lead to

right heart failure

describe the effect of late stage remodelling due to pulmonary hypertension on the left side of the heart

• As the right ventricle dilates, it pushes the interventricular septum backward into the left ventricle. This structural shift protrudes into the left ventricular lumen, mechanically impairing the left heart's ability to fill and function.

what are the consequences of right side heart failure

• reduced cardiac output to the lungs

• retrograde

describe the effect of reduced CO to the lungs as a consequence of right side heart failure

• decreased gas exchange

• hyoxemia

• heightened risk of arrhythmia’s due to increased SNS trying to compensate by increasing heart rate

describe retrograde as a consequence of right side heart failure

• Blood pools in the failing right ventricle, pushing back into the right atrium, and eventually backing up directly into the vena cava

• As this systemic venous pressure rises, the veins in the upper body to bulge, which is most visibly seen as swollen jugular veins in the neck.

• The high pressure continues to back up all the way into the systemic capillaries throughout the body.

• This severe capillary hydrostatic pressure forces fluid out of the blood vessels and into the surrounding interstitial space.

• Because of gravity, this fluid heavily accumulates in the lower extremities, causing pitting edema (severe swelling in the legs, ankles, and feet).