VIVA: Physiology - Circulation and circulating body fluids

Question 1

What is autoregulation of tissue blood flow?

Answer 1

Capacity of tissues to regulate their own blood flow, which remains relatively constant* despite moderate changes in perfusion pressure*

This is achieved by altering vascular resistance*

*needed to pass

Question 2

What are the proposed mechanisms involved in autoregulation?

Answer 2

3 to pass with explanation:
1. Myogenic:
- Intrinsic contractile response of smooth muscle to stretch
- As pressure increases, vascular smooth muscle surrounding the vessels contracts to maintain wall tension (La Place law, T = P x r)
2. Metabolic:
- Production of vasodilator metabolites by active tissues -> vessel vasodilation -> increased flow
3. Endothelial products:
- Vasoconstrictors (e.g. endothelin, TxA2)
- Vasodilators (e.g. nitric oxide, prostacyclin)
4. Circulating neurohumoral substances:
- Vasoconstrictors (e.g. adrenaline, noradrenaline, vasopressin, AT II)
- Vasodilators (e.g. kinins, VIP, ANP)
5. Neural:
- Sympathetic (vasoconstriction with a-adrenergic response, vasodilation with B-adrenergic response)
- Parasympathetic (vasodilation with muscarinic response)

Question 3

What are some local factors that lead to vasodilation?

Answer 3

4 to pass:
- Hypoxia
- Hypercarbia
- Hyperkalaemia
- Acidosis
- Increased lactate
- Increased local temperature
- Adenosine
- Prostaglandins
- Histamine

Question 4

What are baroreceptors and where are they located?

Answer 4

Stretch receptors
Located in the carotid sinus and aortic arch, within the vascular adventitia
Also present in both atria, at the entrance of the SVC and IVC, and within the pulmonary circulation

Question 5

Describe the mechanism of action of baroreceptors

Answer 5

• Sensitive to changes in pulse pressure, with maximal firing at 150mmHg at the carotid sinus
• Stimulated by distension of structures in which they are located (neuronal discharge increases when pressure in this structures rise)*
• Increase in baroreceptor discharge inhibits discharge of sympathetic nerves and excites the vagal (parasympathetic) innervation of the heart*
• Results in vasodilation, venodilation, fall in BP, bradycardia and decreased CO
• Allows rapid adjustments in BP in response to abrupt changes in posture, blood volume, CO or peripheral resistance

*needed to pass

Question 6

Describe the response of baroreceptors in a hypotensive child

Answer 6

The arterial baroreceptors are less stimulated as they are less stretched
Reduced baroreceptor discharge travels via glossopharyngeal and vagus nerves to the medulla
Leads to increase in sympathetic discharge, increased HR, vasoconstriction, and reduced vagal drive

Question 7

What factors affect cerebral blood flow?

Answer 7

• MAP*
• MVP at brain level*
• ICP*
• Local factors: pH, pCO2 (affects constriction and dilation of cerebral arterioles)
• Blood viscosity

*2/3 to pass

Question 8

What is meant by the term autoregulation of cerebral blood flow?

Answer 8

The process by which cerebral blood flow is maintained at a constant level of ~750ml/min despite variations in arterial pressure (MAP 65-140mmHg)

Question 9

What is the Monro-Kellie doctrine?

Answer 9

Volume of blood, CSF and brain tissue must be relatively constant:
- When ICP rises, cerebral vessels are compressed resulting in reduced CBF
- Rise in venous pressure also causes decreased CBF by decreasing effective perfusion pressure and compressing cerebral vessels

Question 10

A patient with a head injury is bradycardic and hypertensive. Describe the mechanism responsible

Answer 10

Cushing reflex:
- Increased ICP compromises blood flow to the medulla *, resulting in increased sympathetic outflow * from vasomotor centre
- BP increased in attempt to restore medullary flow
- Baroreceptors stretch * due to increased BP, resulting in vagal stimulation and thus reflex bradycardia

*needed to pass

Question 11

How is brain perfusion maintained in brain injury?

Answer 11

Aim is to maintain CPP
With high ICP, needed to increase MAP to maintain CPP (CPP = MAP - ICP)
Raised MAP results in systemic hypertension, producing reflex bradycardia via baroreceptor reflex and vagal stimulation

Question 12

What proportion of the total body oxygen does the brain consume?

Answer 12

20% (despite brain weight being only 2% of body weight)

Question 13

What energy substrates can be used by the brain?

Answer 13

Glucose*
Glutamate
In prolonged starvation amino acids

*needed to pass

Question 14

What are the physiological responses to losing 1L of blood in adult?

Answer 14

Acutely:
- Decreased venous return -> reduced baroreceptor stimulation* -> catecholamine release, decreased vagal tone -> tachycardia and vasoconstriction

12-72hrs:
- Renal hypoperfusion -> activation of renin angiotensin system* -> fluid shifts (isovolaemic anaemia)
- Longer term renal compensation via aldosterone -> increased Na+ and H2O retention

3-4 days:
- Hepatic synthesis of proteins

> 10 days:
- Increased erythropoiesis by increased EPO release

Question 15

What is the coronary blood flow at rest?

Answer 15

250ml/min or 5% of cardiac output

Question 16

Describe coronary artery blood flow during the cardiac cycle

Answer 16

• In L coronary there is greater flow in diastole compared with systole, due to higher pressures required in the LV to overcome aortic pressure during systole
• LV subendocardium is most vulnerable to reduced coronary artery blood flow as it only gets diastolic flow
• R coronary flow is continuous throughout systole and diastole due to lower RV pressures

Question 17

What chemical factors may cause coronary vasodilation?

Answer 17

• Hypoxaemia*
• Hypercarbia*
• Hyperkalaemia
• H+*
• Lactate*
• Adenosine
• Adenine nucleotides
• Prostaglandins

*2/4 to pass

Question 18

What receptors govern coronary blood flow?

Answer 18

Coronary arterioles have:
- Alpha receptors: vasoconstriction
- Beta receptors: vasodilation
- Cholinergic receptors: vasodilation
- Noradrenaline constricts coronary arteries (although noradrenergic nerves caused increased HR and contractility, producing metabolites which act as vasodilators; this is the effect that maintains coronary flow during hypotension)

Question 19

What percentage of cardiac output goes to the kidneys?

Answer 19

~25% of CO in adult
1.2-1.3L/min

Question 20

How is renal blood flow regulated?

Answer 20

1. Substances/chemicals*:
   - Noradrenaline: renal vessel constriction, stimulates renal nerves to increase renin secretion
   - Dopamine: renal vasodilation
   - AT II: arteriolar constrictor
   - Prostaglandin: increased cortical flow, decreased medullary flow
   - ACh: renal vasodilation
   - High protein: increased blood flow
2. Renal nerves:
   - Stimulation increases renin secretion, juxtaglomerular sensitivity, Na+ reabsorption, renal vasoconstriction
   - Strong stimulation of sympathetic nerves (noradrenaline) decreases flow
   - Decreased BP causes vasoconstriction
3. Autoregulation:
   - Renal vascular resistance varies with pressure to keep renal blood flow relatively constant
   - Present in denervated kidney, but not if drugs that paralyse vascular smooth muscle present
   - Factors: direct contractile response of vascular smooth muscle, nitric oxide, AT II

*3/6 substances/chemicals + nerve or autoregulation with example

Question 21

How can renal blood flow be measured?

Answer 21

1 needed to pass:
1. Fick principle:
- Amount of substance taken up / unit time
2. PAH clearance:
- Used to measure renal plasma flow (completely removed from renal blood in single pass)
3. Renal blood flow:
- Using plasma flow and Hct

Question 22

Describe the differences in regional blood flow within the kidney

Answer 22

A-V O2 difference for kidney = 14ml
Cortical blood flow = 5ml/g/min (little O2 consumption)
Medulla blood flow lower (outer = 2.5ml/g/min, inner = 0.6ml/g/min) but maintains osmotic gradient

Question 23

Describe the receptors that response to a fall in blood pressure

Answer 23

1. Baroreceptors*:
   - In carotid sinus, aortic arch, atria
   - Reduced stretch -> increased sympathetic stimulation -> tachycardia and generalised vasoconstriction (with sparing of brain and heart)
   - With increased shock, paradoxical bradycardia can occur with unmasking of the vagal depressor reflex, then tachycardia again with further shock
2. Chemoreceptors*:
   - In carotid and aortic bodies
   - Stimulated by reduced blood flow and acidosis
   - Stimulates vasomotor areas in medulla with increase in vasoconstriction

*needed to pass + concepts

Question 24

Describe the non-cardiovascular compensatory responses to shock

Answer 24

Renal*:
- Efferent arterioles more constricted than afferent
- Renal plasma flow decreased more than GFR (filtration fraction increases)

Na+ retention:
- Retained nitrogenous products of metabolism (uraemia)

AT II:
- Plasma renin causing AT II release -> maintains BP and causes stimulation in thirst centre in brain

Vasopressin:
- Retains Na+ and H2O

Aldosterone:
- Stimulated by circulating AT II and ACTH
- Helps retain Na+ and H2O

Adrenal stimulation:
- Secretion of catecholamines

Increased circulation of NA:
- Increased discharge of sympathetic NA nerves

*needed to pass + 2 others

Question 25

What is hypovolaemic shock?

Answer 25

Systemic hypoperfusion due to reduced effective circulating blood volume, resulting in impaired tissue perfusion and cellular hypoxia

Question 26

Describe the mechanisms of venous return to the heart

Answer 26

1. Thoracic pump*:
   - Inspiration resulting in negative pressure in the thorax and positive pressure in the abdomen
   - Blood flow towards the heart because of venous valves
2. Effect of heart beat:
   - During systole, AV valves are pulled downward -> increases the capacity of the atria
3. Muscle pump:
   - Contraction of muscles around veins in the limbs during activity
4. Differential resistance:
   - Resistance of large veins near the heart is less than peripheral veins

*needed to pass + one other

Question 27

What factors might affect CVP in a patient in intensive care?

Answer 27

Decrease CVP*:
- Fluid loss (e.g. third spacing)
- Blood loss
- Loss of arterial tone
- Loss of muscle pump (e.g. when ventilated)
- Myocardial depression (e.g. acidosis)
- Poor ventricular filling (e.g. tachycardia)

Increase CVP*:
- Excessive fluid replacement
- Other pre-existing conditions (e.g. CCF)
- Positive pressure ventilation
- Increased thoracic pressures
- Vasopressor use

• one example from each needed to pass

Question 28

What is the value of mean CVP in normal individuals?

Answer 28

4.6-5.8mmHg or 6-8 cm H2O

Question 29

Describe the factors controlling blood flow through skeletal muscle during exercise

Answer 29

• Increased flow is mainly due to local regulation * (due to chemical effects on muscle arterioles leading to vasodilation)
• Response to reduction in oxygen in muscle tissue * (hypoxia results in release of vasodilators e.g. adenosine)
• Other controlling factors include sympathetic vasoconstrictor nerves and circulating adrenaline

*needed to pass

Question 30

What circulatory changes occur in the body during exercise and why?

Answer 30

• Increased blood flow through skeletal muscle, mostly due to local production of vasodilatory substances (e.g. adenosine)
• Increased CO, HR and contractility due to increased sympathetic discharge
• Contraction of peripheral arterioles not in skeletal muscle due to increased sympathetic discharge (coronary and cerebral systems spared)
• Contraction of capacitance vessels (e.g. veins) due to increased sympathetic discharge resulting in increased venous return, filling pressure *, CO

*needed to pass

Question 31

What factors can decrease coronary artery blood flow?

Answer 31

1. Physiologic:
   - Tachycardia * (due to shorter diastole; L coronary flow is affected in particular)
2. Pathologic:
   - AS (increased LV pressures required to overcome stenosis and decreased flow)
   - Vasospasm
   - Coronary artery disease
   - Heart failure
   - Increased venous pressure
   - Reduced coronary perfusion pressure

*needed to pass + 2 pathologic factors

Question 32

What are the basic factors which determine the rate of flow of blood through a blood vessel?

Answer 32

Poiseulle’s Law and formula describe these factors:
- Proportional to pressure differential and radius to the 4th power *
- Inversely proportional to length of tube and viscosity of fluid
- Flow = (Pa - Pb) x (πr^4/8nL)

*needed to pass + 2 other factors

Question 33

What factors cause turbulent flow in a blood vessel?

Answer 33

Expressed by Reynold’s number, where the higher the number the greater the probability of turbulence (usually occurs with a Reynold’s number of 2000-3000):
- Proportional to fluid density, diameter of tube and velocity of flow
- Inversely proportional to viscosity of fluid
- Re = pDV/n *

*3/4 factors to pass