Learning MRCS A - physiology /medicine

- When ICP > arterial pressure ⇾ compression of cerebral arterioles ⇾ cerebral ischaemia. 

• - What:
•    + initially: ↑ ICP ⇾ stepwise activation of sympathetic NS     
•          ⇾ peripheral vascular resistance ⇾ HTN, CO↑           
•                ⇾ detected by aortic arch baroreceptors 
•    + 2nd stage: ⇾ activation of parasympathetic NS

- a serious development, indicates imminent coning or other terminal events if not resolved quickly.

(NS nervous system)

- physiological nervous system response to acute elevations of intracranial pressure (ICP) 

• - results in Cushing triad
•    + widened pulse pressure (increasing systolic, decreasing diastolic)
•    + bradycardia
•    + irregular respirations.

(mnemonic GFR - ACD)

• - Zona glomerulosa (on outside): mineralocorticoids, mainly aldosterone
• - Zona fasciculata (middle): glucocorticoids, mainly cortisol
• - Zona reticularis (on inside): androgens, mainly dehydroepiandrosterone (DHEA)

• a)Renin
• - Released by JGA cells in kidney 
• - Hydrolyses angiotensinogen -> angiotensin I
• - Factors stimulating renin secretion
•     + * Low BP
•     + * Hyponatraemia
•     + Sympathetic nerve stimulation
•     + Catecholamines
•     + Erect posture
•     + Angiotensin

• b) ACE 
• - in lung converts angiotensin I → angiotensin II
• - effects: main 2: 
•    * increase BP 
•       + increase sympathetic activity
•       + arteriolar vasoconstriction 
•    * increase circulation volume from water and salt retention
•       + stimulates aldosterone 
•       + stimulates ADH release
•       + stimulates thirst

• c) Aldosterone
• - Released by the zona glomerulosa
• - in response to raised angiotensin II, potassium, and ACTH levels 

- Causes retention of Na+ in exchange for K+/H+ in distal tubule

• d) ADH
• - pituitary gland, posterior lobe - ADH secretion 
• - acts on collecting duct - water absorption 

e) ((ACTH regulates cortisol))

• - α-1, α-2: vasoconstriction
• - β-1: increased cardiac contractility and HR
• - β-2: vasodilatation
• - D-1: renal and spleen vasodilatation
• - D-2: inhibits release of noradrenaline 

(dopamine)

• Inotrope & Cardiovascular receptor action
• - Adrenaline: α-1, α-2, β-1, β-2 (β agonist at lower dose, α at higher dose)
• - Noradrenaline: α-1,( α-2), (β-1), (β-2)
• - Dobutamine: β-1, (β 2)
• - Dopamine: (α-1), (α-2), (β-1), D-1,D-2

(Minor receptor effects in brackets)

• - catecholamine type agents: adrenaline, norad, dopamine   
•    + dobutamine: synthetic cathecholamine
• - phosphodiesterase inhibitors: milrinone

• - work primarily by increasing cardiac output
• - distinguised from vasoconstrictor when problem is vasodilatation

• - works by increasing cAMP levels
•     + by adenylate cyclase stimulation 
• - then: intra-cellular calcium ion mobilisation 
•     -> increase force of contraction 

- dopamine: both HR + BP raised -> less overall myocardial ischaemia

• beta adrenergic receptor agonist at lower doses
• an alpha receptor agonist at higher doses

(lower, bắt đầu là beta, mạnh hơn thành alpha)

• - causes dopamine-receptor mediated renal and mesenteric vascular dilatation and beta 1 receptor agonism at higher doses
• - both HR + BP raised -> less overall myocardial ischaemia

• a predominantly beta 1 receptor agonist
• weak beta 2 and alpha receptor agonist properties

• an alpha receptor agonist
• & as a peripheral vasoconstrictor

• e.g. milrinone 
• specifically on the cardiac phosphodiesterase
• -> increase cardiac output.