Physiology 2 Flashcards
Which hormones act as effectors to regulate plasma vol and MAP?
Renin-Angiotensin-Aldosterone system (RAAS), Atrial Natrieretic Peptide (ANP) and The Antidiuretic hormone (ADH)
Total body fluid = ?
Intracellular fluid + extracellular fluid (ECF)
ECFV = ?
Plasma Volume (PV) + Interstitial Fluid Volume (IFV)
What is extracellular fluid?
Fluid that bathes the cells and acts as the go between between the blood and body cells
What are the two main factors that affect ECFV?
Water excess or deficit and sodium excess or deficit
How do hormones regulate ECFV?
They regulate the water and salt balance in our bodies
What should the ratio of water input to water output be in a healthy person?
1:1
Where is renin released from?
The kidneys
What does renin do?
Stimulates the formation of angiotensin I in the blood from angiotensinogen (produced by liver)
What does Angiotensin I do?
Is converted to angiotensin II by angiotensin converting enzyme (ACE - produced by pulmonary vascular endothelium)
What does angiotensin II do?
- Stimulates release of aldosterone from the adrenal cortex
- Causes systemic vasoconstriction - increases TPR (also stimulates thirst and ADH release)
What does aldosterone do?
Acts on the kidneys to increase sodium and water retention - increases plasma vol and thus BP
What is the rate limiting step for RAAS?
Renin secretion
RAAS is regulated by mechanisms which stimulate Renin release from where in the kidney?
the juxtaglomerular apparatus
What are the renin releasing mechanisms?
- Renal artery hypotension - caused by systemic hypotension
- Stimulation of renal sympathetic nerves
- Decreased sodium conc in renal tubular fluid - sensed by macula densa
What are the roles of ANP?
- Causes secretion of salt and water in the kidneys - reduces blood vol and BP
- Acts as a vasodilator - decreases BP
- Decreases renin release
- Acts as a counter-regulatory mechanism for RAAS
Where is ANP stored?
atrial myocytes
When is ANP released?
Released in response to atrial distension (hypervolaemic states)
Where is ADH synthesised and stored?
Synthesised - hypothalamus
Stored - posterior pituitary
What is ADH secretion stimulated by?
- Reduced ECFV
2. Increased ECF osmolarity
What is plasma osmolarity monitored by?
Osmoreceptors mainly in the brain close to the hypothalamus
What are the roles of ADH?
- ADH acts in kidney tubules to increase the reabsorption of water - increases ECF and plasma volumes and hence CO and BP
- Also causes vasoconstriction - increases TPR and BP - effect is small in normal people but becomes important in hypovolaemic shock
How is short term regulation of MAP achieved?
Baroreceptors
What is blood pressure?
The outwards (hydrostatic) pressure exerted by the blood on blood vessel walls
In what fashion is blood flow in normal arteries?
Laminar
First Kortokoff sound is heard when?
At peak systolic pressure
When is diastolic pressure recorded?
The disappearance of the Kortokoff sounds
What drives the blood around the systemic circulation?
Pressure gradient between the aorta and the right atrium
Pressure gradient = ?
Mean Arterial Pressure (MAP) - Central Venous (right atrial) Pressure (CVP)
What is MAP?
The average arterial BP during a single cardiac cycle, which involves contraction and relaxation of the heart
MAP = ?
[(2 x diastolic pressure) + systolic pressure] / 3
How can MAP be estimated?
By adding diastolic blood pressure to 1/3rd of the pulse pressure (difference between SBP and DBP)
What is the normal range of MAP?
70 - 105 mmHg
What is the lowest MAP needed to perfuse the coronary arteries, brain, and kidneys?
60mmHg
Why must MAP be regulated within a narrow range?
Ensures:
- Pressure is high enough to perfuse internal organs
- Pressure is not too high as to damage the blood vessels or place extra strain on the heart
MAP (not to do with blood pressure) = ?
CO x TPR
CO = ?
SV x HR
What is total peripheral resistance?
Sum of resistance of all peripheral vasculature in the systemic circulation
What are the major resistance vessels?
Arterioles
What is the baroreceptor reflex?
Baroreceptors -> medulla -> Effectors
What happens to venous return when a normal person suddenly stands up from lying down?
It decreases (effect of gravity)
What happends to MAP and baroreceptors when a normal person stands up suddenly from lying down?
MAP transiently decreases - reduces rate of firing of baroreceptors
What happens to the vagal and sympathetic tones of the heart when a normal person stands up suddenly from lying out?
Vagal tone decreases and sympathetic tone increases - increases heart rate and SV
Sympathetic constrictor tone increases - increases TPR and venous return and SV
What is postural hypotension?
Hypotension that results from failure of baroreceptor responses to gravitational shifts in blood, when moving from horizontal to vertical position
How is MAP controlled in the long term?
Blood volume
Which blood vessels contain most of the blood vol during rest?
Veins
How is TPR regulated?
TPR is regulated by smooth muscles
Where is the main site of TPR?
Arterioles
Resistance to blood flow is? (equation in words)
Directly proportional to blood viscosity and length of blood vessel and inversely proportional to the radius of blood vessel to the power of 4
What does extrinsic control of vascular smooth muscle involve?
Nerves and hormones
What innervation is in vascular smooth muscles and what is the neurotransmitter?
Sympathetic innervation with noradrenaline as the neurotransmitter
What is vasomotor tone?
The vessels are partially constricted at rest
What is vasomotor tone caused by?
Tonic discharge of sympathetic nerves resulting in continuous release of noradrenaline
How extensive is parasympathetic innervation of arterial smooth muscles?
No significant parasympathetic innervation
What happens when adrenaline acts on alpha receptors?
Vasoconstriction
What happens when adrenaline acts on beta receptors?
Vasodilation
Where are alpha receptors found?
Predominantly in skin, gut and kidney arterioles
Where are beta receptors found?
Predominantly in cardiac and skeletal muscle arterioles
Why are the beta and alpha receptors predominatly in different areas?
To aid with strategic redistribution of blood
What other hormones cause vasoconstriction?
Angiotensin II and ADH (vasopressin)
Can intrinsic controls override extrinsic controls?
Yes
What factors cause relaxation of arteriolar smooth muscles -> vasodilation?
Decreased local PO2, Increased local PO2, Decreased local pH, Increased extracellular calcium, Increased osmolarity of ECF, Adenosine release (from ATP)
When are humoral agents released?
In response to tissue injury or inflamm
What humoral agents cause vasodilation?
Histamine, Prostaglandins, Bradykinin, Nitric oxide
Where is NO produced?
Produced by the vascular endothelium from L-arginine through enzymatic action of Nitric Oxide Synthase (NOS)
What causes release of calcium in vascular endothelial cells and the subsequent activation of NOS?
Sheer stress on vascular endothelium - result of increased flow - flow dependent NO formation
What else can induce NO formation?
Chemical stimuli
What is the mechanism of smooth muscle relaxation using NO?
NO diffuses from the vascular endothelium into the adjacent smooth muscle cells where it activates the formation of cGMP - second messenger for signalling of smooth muscle contraction
Which humoral agents cause vasoconstriction?
Serotonin, Thromboxane A2, Leukotrienes and Endothelin
By what is endothelins production stimulated?
Angiotension II and vasopressin
How does temperature affect vascular smooth muscle?
Cold : vasoconstriction
Warmth: vasodilation
How does stretch affect vascular smooth muscle?
If MAP rises, resistance vessels automatically constrict to limit flow and vice versa
How do you increase venous return??
Increase venomotor tone, increase skeletal muscle pump, increase blood vol, increase resp pump
What effects does increasing venous return have?
Increased atrial pressure, increased EDV, increased SV
What does increased venomotor tone increase?
Venous return, SV and MAP
What is the skeletal muscle pump?
Large veins lie between skeletal muscles. Contraction of these aids venous return. One-way venous valves allows blood to move forward towards the heart. Muscle activity increases venous return to the heart
What happens to nerve activity when exercising?
Sympathetic nerve activity increases - HR and SV increase - increases CO
Sympathetic vasomotor nerves reduce flow to kidneys and gut - vasoconstriction
In skeletaland cardiac muscle, metabolic hyperaemia overcomes vasomotor drive - vasodilation
What happens to BP when exercising?
Systolic BP increases due to increased CO. Metabolic hyperemia decreases TPR and decreases DBP - post exercise hypotensive response
What effects does sympathetic stimulation have on the heart?
Sympathetic stimulation increases heart rate by increasing the rate of firing of SAN and decreasing AV nodal delay
Force of contraction is also increased
Effect of sympathetic stimulation on pacemaker cells?
Slope of pacemaker potential increases. Pacemaker potential reaches threshold quicker - frequency of APs increases
Where do the right and left coronary arteries arise from?
Base of aorta
Where does the coronary venous blood darin into?
The right atrium via the coronary sinus
What happens if the coronary arteries block more distally?
The amount of cardiac muscle deprived of blood supply (and thus oxygen) is reduced
What are the special adaptations of coronary circulation?
High capillary density, high basal blood flow, high oxygen extraction under resting conditions, extra oxygen is supplied by increasing blood flow
How is coronary blood flow controlled?
By intrinsic and extrinsic mechanisms
What does decreased PO2 do to the coronary arterioles?
Causes vasodilatation
What is the main vasodilator of the coronoary arterioles?
Adenosine
What innervation supplies the coronary arterioles?
Sympathetic vasoconstrictor nerves
What is different about these nerves (sympathetic nerves in coronary arterioles)?
they’re overridden by metabolic hyperaemia as a result of increased heart rate and stroke vol so sympathetic stimulation of the heart results in coronary vasodilation despite direct vasoconstrictor effect (functional sympatholysis)
Which receptors and neurotransmitter causes vasodilation of the coronary arteries?
Adrenaline activates the beta 2 adrenergic receptors
What arteries supply the brain?
internal carotids and vertebral arteries
What is the basilar artery?
Artery formed by two vertebral arteries
What is the circle of willis formed by?
The basilar and carotid arteries anastomose to form the circle of willis
What is special about the circle of willis?
Cerebral perfusion should be maintained even if one of the carotid arteries gets obstructed
What are the two types of stroke?
haemorrhagic and ischaemic
What happens in a haemorrhagic stroke?
Blood leaks out of a damaged artery wall
What happens in an ischaemic stroke?
Blood clot. Forms on atheroma on artery wall or comes from another part of the body and get stuck
What do the terminal arterioles do?
Regulate regional blood flow to the capillary bed in most tissues
What are the methods of transport across the capillary wall?
Water soluble substances go through the water-filled pores
Lipid soluble substances go through the endothelial cells
What is transcapillary flow driven by?
Pressure gradients across the capillary wall
Which forces favour filtration in transcapillary fluid flow?
- Pc: capillary hydrostatic pressure
- interstitial fluid osmotic pressure
Which forces oppose filtration in transcapillary fluid flow?
- Capillary osmotic pressure
- Interstitial fluid hydrostatic pressure (-ve in some tissues)
NFP (net filtration pressure) =?
Forces favouring filtration - forces opposing filtration
When do Starling forces favour filtration?
At the arteriolar end
When do Starling forces favour reabsorption?
At the venular end
What type of ischaemia is there in chronic stable angina?
Demand led ischaemia
What will a patient say that cardiac chest pain feels like?
‘Heavy feeling’
‘Weight on chest’
‘Pressure, tightness’
What is an acute coronary syndrome?
An acute presentation of coronary artery disease
What are the two different types of MI?
ST elevation and non ST elevation MIs
Which factors affect plaque rupture?
Sudden changes in intraluminal pressure or tone Lipid content of plaque Thickness of fibrous cap Plaque shape Mechanical injury
Key history points of an MI?
- Severe crushing central chest pain
- Pain radiates to jaw and arms (esepcially the left)
- Similar to angina but more severe and prolonged - also not relieved by GTN
- Associated with sweating, nausea and vomitting
What are the ECG changes in acute STEMI?
ST elevation
T wave inversion
Q waves
Which leads are associated with an inferior MI?
II, III, AVF
Which leads are associated with an anterior MI?
V1-V6
Which leads are associated with an anteroseptal MI?
V1 - V4
Which leads are associated with an anterolateral MI
I, AvL, V1-V6
What investigations can confirm an MI?
Creatinine kinase - peaks in 24 hours after MI
Troponin - highly specific for cardiac muscle damage - can detect tiny amounts of myocardial necrosis
What are the early treatments of STEMI?
Analgesia - diamorphine IV Anti-emetic - IV 300mg of aspirin and clopidogrel GTN - if BP > 90mmHg Oxygen if hypoxic Primary angioplasty Thrombolysis if angioplasty isn't available withing 90 mins
Which medications should be continued after a STEMI?
Aspirin should be continued long term and clopidogrel should be continued for up to 4 weeks
What are the three indications for reperfusion therapy?
- Cardiac chest pain
- ECG changes
- No contraindications `
What are the risks of thrombolytic therapy?
Failure to re-perfuse
Haemorrhage
Hypersensitivity
What are the complications of an acute MI?
Death
Arrhythmic complications
Structural complications
Functional complications
What are the structural complications of an acute MI?
Cardiac rupture Ventricular septal defect Mitral regurgitation Inflamm Acute pericarditis Dressler's syndrome
What is the arrhythmic complication of an acute MI?
Ventricular fibrillation
What are the functional complications of an acute MI?
Acute ventricular failure
Chronic cardiac failure
Cardiogenic shock
