Heart And Lung Physiology Flashcards
What is the structure and function of the heart and lung system?
Consists of the heart and blood vessels (circulatory system)
Function - Transport mechanism:
- oxygen
- nutrients - glucose, electrolytes
- antibodies / white blood cells to sites of infection
- hormones
- waste products of metabolism
- heat
What is the circulatory system?
Deoxygenated into right side through vein of heart then out of pulmonary artery through lungs bringing oxygenated blood back into left of heart.
Portal system - to liver and a second direct portal system to hypothalamus and pituitary in the brain.
How does cardiac conduction occur?
Autonomous beating
AV node is the only electrical component of the heart, everything else is insulated.
What is an ECG?
12 leads attached to body looking at different areas of heart.
Resting cells are polarised (negative potential) contraction leads to depolarisation.
What happens during a cardiac contraction?
Inner cell membrane is more negative than outside.
Signal allows sodium and calcium influx, normally have a slight leakage of potassium out of cell, but now Potassium channels close.
Disturbances in electrolyte concs affects how quick they can go in and out of cell, so leads to heart defects.
Polarised cell – intracellular negative. Unstimulated-resting potential.
Depolarised cell – influx of positive ions, stimulated-action potential
How does BP reflect the cardiac cycle?
Pressure changes in ventricles over time. Diastolic - ventricles relaxing, systolic - ventricles contracting.
Top number in BP is systole and bottom is diastole.
What is the structures of the arteries?
Arteries: Both have central lumen but arteries have elastic layer - expand and contract with ventricles to force blood through.
Veins: Aren’t under the same pressure from the heart, so have periodic valves controlled by muscle to prevent back flow - no necessity for elastic
What is the capillary bed?
One cell layer thick, allows nutrients and fluids to pass out. Blood in through atrial side has a higher hydrostatic pressure - pushes nutrients out.
As things are lost through the capillary then the oncotic pressure increases allowing waste products and fluid to reenter the capillary on the venous side back to the superior vena cava.
How is blood pressure regulated?
Cardiovascular centre located in medulla oblongata regulates blood pressure.
BP maintained by changes in:
- cardiac output – heart rate/stroke volume
- resistance to blood flow – vasodilation / vasoconstriction
BP controlled by:
- Sympathetic nervous system – increases BP - increase heart rate &
vasoconstriction
- Parasympathetic nervous system – decreases BP - decreases heart
rate & vasodilation
Detected by:
- Baroreceptors – detect arterial BP (carotid sinus / aortic arch / right
atrium)
- Chemoreceptors – detect O2 & CO2 levels (carotid bodies and aortic
bodies located near the carotid sinus and aortic arch)
BP Also Regulated by:
Increase BP:
1. Kidney
- RAAS: Increased sodium/water retention & angiotensin II
causes vasoconstriction.
- ADH: Increases water retention, increasing fluid volume in vascular
system - increases pressure
2. Adrenaline / Noradrenaline
– increase heart rate and vasoconstriction, thus increases pressure
Decrease BP:
- ANP – Vasodilation. Inhibits RAAS.
- Nitric oxide - vasodilation
What is cardiovascular disease (atherosclerosis)?
Atherosclerosis effects arteries in the heart, brain and peripheral tissues.
It is the deposition of lipid and matrix proteins in the arterial wall (medium to large arteries) - anywhere in the body, but causes larger issues in certain areas. Leads to narrowing of the vessel lumen and so a reduced blood supply.
- Heart – causes coronary heart disease
- Brain – causes stroke
Plaques get laid down in arteries as you get deposition of lipids. This causes an inflammatory response and macrophages to accumulate at the site, these get lipid-ladened, termed ‘foaming macrophages’.
The lipid layer and macrophages break through the basement layer and elastic layer, allowing smooth muscle to migrate out forming a cap over the top of the atherosclerotic plaque.
Once covered the smooth muscle cells lay down collagen and other intracellular matrix proteins, making the cap extremely stable, to protect the lipid core.
Sometimes a balance between smooth muscle cells and the inflammatory response is compromised as the macrophages break down the intracellular proteins, thinning the cap. When this becomes too thin it will rupture. Thus this is a tight balance.
What are risk factors for CVD?
Age - older Gender - men Race Family History Pre existing CVD Smoking Cholesterol (fatty food) Hypertension Obesity Diabetes Mellitus Low physical activity
Biochemical:
- Homocysteine
- hsCRP
- IL-6
- Fibrinogen
- Micro RNA (miRNA)
What is coronary heart disease?
Failure of the coronary circulation to meet the demands of the heart (increased demand/decreased supply)
Caused by:
- cardiovascular disease - atherosclerosis (coronary arterial disease)
- Vasospasm, anaemia, arrhythmias -heart lacking adequate
blood supply
Leads to lack of oxygen - Ischaemia
- So is also called ischaemic heart disease (IHD)
- End result of CHD is cell death
- Prolonged ischaemia – cell death (necrosis)
- May also get collagen scarring, affecting how it can pump.
- MI is most commonly a result of CAD affecting arteries that feed
heart muscle
- Depends where it occurs as to how much of the heart is affected
What is coronary artery disease?
Atherosclerosis in coronary arteries causing inadequate oxygen supply to the heart.
If smooth muscle accumulation during cap formation is exposed to shearing forces, it can rupture. This is more likely to occur in an area under high pressure that is curved slightly, eg aorta (under very high pressure).
Rupturing causes formation of a thrombus which attracts platelets, narrowing the lumen even more.
Eventually get an ST elevated MI, where the entire lumen has been occluded, which can be seen on an ECG. Whereas in a non-STEMI a very small area of the vessel is not occluded.
Sometimes the clots can get a way giving a thrombotic clot which passes into the smaller arteries completely blocking those. Thus it is a spectrum from stable angina the STEMI.
This leads to:
1. Stable angina:
- partial occlusion of cardiac artery due to lipid plaques.
- Enough blood can get through at rest, but unable to supply
oxygen if increased demand (exercise, stress)
2. Acute coronary syndrome (ACS)
3. MI is the end point
How is ACS diagnosed in the lab?
- ECG changes - main, but some events don’t cause ECG changes, or of previous events mean the ECG hasn’t returned to normal
- Biochemical Cardiac Markers of CVD
- Cardiac enzymes
- Myoglobin
- Troponins
What are the cardiac enzymes used to diagnose ASC?
ALT (alanine aminotransferase)
- Unspecific - liver, skeletal and cardiac muscle, kidney.
- Cytoplasm of cells
- Increased in plasma following circulatory failure, MI.
- X10 URL
AST (aspartate aminotransferase)
- Unspecific - liver, skeletal and cardiac muscle, kidney.
- Cytoplasm of cells
- Increased in plasma following circulatory failure, MI.
- X10 URL
LDH (Lactate dehydrogenase)
- Wide tissue distribution
- Due to rupture of cells releasing enzymes.
- Labs measure total LDH - though there are five isoforms: LDH1 – LDH5.
LDH1 – significant in MI
- Measure total LDH
- X10 URL
CK (Creatine Kinase)
- Skeletal and cardiac muscle, brain.
- Dimer of two subunits M or B.
- 3 isoforms: MM (skeletal and cardiac), MB (35% of cardiac activity, 5%
skeletal), BB (brain) - some labs measure total, some look specifically at
MB - higher % in heart than skeletal
- Measure CK and CK-MB (both raised in muscle damage)
What is myoglobin?
Present in all muscle
Haem protein – oxygen transport, binds and stores oxygen in muscles, demanded during exercise.
Found in cytoplasm
What are troponins?
Main test for MI
Three kinds involved in muscle contraction allows actin and tropomysin in muscle cells to slide over each other:
- Troponin T – binds to tropomyosin
- Troponin I – inhibitor of ATPase
- Troponin C – binds calcium
One of the effects of an electrical signal is for Ca to enter cell; this binds to Trop C, altering the conformation of Trop I and T such that they move away from the actin and myosin filaments allowing them to slide over each other and the muscle to contract.
Trops are found in all muscle cells, but there are cardiac specific isofoms of T and I. Trop T and I are therefore measured in the labs as markers for cardiac damage (cardiac specific isoforms, written as cTrop T and cTrop I) - main advantage over enzyme measurements.
Troponin I is more specific; skeletal troponin T isoforms cross react in cardiac Troponin T assay. High sensitive assays (hsTnT / hsTnI) – lower detection limits, so can measure smaller levels in the blood, thus can identify if someone’s had a cardiac injury earlier.
How does the detection of each cardiac marker compare?
Detection time depends on:
- Size
- Cellular location
- Plasma clearance
As muscle cells die they allow release of intracellular components; how quickly they are resleased depends on where in the cell they were located and how quickly they are cleared by liver/kidney.
Each enzyme has different characteristics.
Rises: Peaks: Stays risen:
Myoglobin: 2-4 hr 8-10 hrs 1 day
AST: 6-8 hr 24-48 hrs 3-4 days
LDH: 12-24 hr 48-72 hrs 7-12 days
CK-MB: 2-4 hr 18 hrs 1-2 days
Troponins: 4-6 hr 12-24 hrs 7-10 / 3-10 days
- Trop T elevates quickly and stays elevated for a long time
- CKMB levels are measured if you think someone has had a
second event
What are the NICE guidelines for detection of a cardiac event?
NICE Guidance CG95. Chest pain of recent onset (2010):
- Take a blood sample for trop I or trop T on initial assessment in
hospital. These are the preferred biochemical markers to
diagnose acute MI. - Take a second blood sample for trop I or T measurement 10–12hours
after the onset of symptoms. - Do not use biochemical markers such as natriuretic peptides and high
sensitivity CRP to diagnose acute coronary syndrome.
NICE Guidance DG15. Acute MI:early rule out using high sensitive Troponin (2014)
- Immediate test and 3 hours later - don’t have to admit the patient
while waiting for result and if 3 hour test comes back okay they can go -
good for 4 hour wait time target
What are other causes of a raised troponin?
Trauma
Congestive heart failure–acute and chronic
Hypertension
Hypotension, often with arrhythmias
Renal failure - Trop cleared by kidneys, so indicates worse renal prognosis
Critically ill patients, esp with diabetes
Hypothyroidism
Myocarditis
Pulmonary embolism
Sepsis
Burns, esp if total burn surface area > 30%
Amyloidosis
Acute neurological disease, including CVA
Rhabdomyolysis with cardiac injury
Vital Exhaustion
Polymyositis
Shock
What is heart failure?
Failure of heart output to meet demand. The heart isn’t pumping frequently/strongly enough leading to back pressure throughout body.
If right side of the heart isn’t pumping enough the back pressure spreads throughout the body, increasing the hydrostatic pressure in the blood vessels. This causes fluid to leak out leading to oedema and ascites - seen commonly as swelling around ankles and legs (due to gravity).
If it happens to the left side of heart, fluid builds up around the heart, so lungs cant work properly leading to shortness of breath and fatigue.
Symptoms:
- SOB, fatigue, oedema
Causes:
- Cardiomyopathy
- Inflammation to heart cells
- Valvular heart disease
- Ischaemic heart disease (atherosclerosis)
How is heart failure diagnosed?
Echocardiogram – gold standard
Markers of Heart Failure: BNP:
- Brain natriuretic peptide (BNP): Secreted from ventricles. Pressure in
HF causes ventricles to enlarge, leading to increased BNP release.
- BNP is secreted primarily from ventricules as a prohormone (proBNP).
During HF the ventricles expand, causing proBNP to be released and
cleaved at the N terminus into two fragments; BNP (the active form)
and NT-proBNP. There are lab immunoassays for both of these;
clinically both are the same - doesn’t matter which you measure.
BNP is much less stable though, so have to be more careful with
sample collection - can require the sample to be frozen. - Increased in:
- cardiac failure
- ventricular hypertrophy, ischaemia, tachycardia, sepsis,
COPD, hypoxaemia, renal disease, >70yrs
- Useful ‘rule-out’ test – echo referral only if high
- Negative result excludes heart failure
- Reduced levels:
- Diuretics, ACE inhibitors, Beta-blockers, ARB, Aldosterone
antagonists - Prognostic indicator in heart failure
- Diuretics, ACE inhibitors, Beta-blockers, ARB, Aldosterone
What is hypertension?
BP >140/90 mmHg
Risk factor in CVD – CHD or stroke
Essential hypertension – unknown cause (most common)
Endocrine hypertension - Conn’s, Cushings, phaeochromocytoma.
Biochemical markers:
- No specific biochemical markers for hypertension
- Diagnosing endocrine causes
- Management/monitoring treatment (many patients are on eg diuretics,
that lead to real issues)
- renal function
- electrolyte disturbance
What is thrombotic disease?
Thrombosis - formation of blood clot in artery/vein by process of coagulation
Predisposing factors:
- injury to vessel wall
- Reduce blood flow
- Abnormal coagulation
Thrombus can break away to form an embolus.
- Arterial thrombus/embolus: MI, stroke, TIA - Venous thrombus/embolus: DVT, Pulmonary embolus (PE).
Diagnosis:
- Arterial – clinical
- Venous - D Dimer (fibrin degradation product). Rule out test in
combination with risk calculators.
