• Q - cardiac output, pumps blood into the C_a, the arteries (less capacitance than C_v, and therefore P_a rises faster than C_v). Blood flows from arteries to R, the arterioles (resistance vessels), into the veins (C_v, and finally back into the heart. 
• Therefore, P_a-P_v = Q x R, or that blood pressure is depedent on cardiac output and systemic vascular resistance 
• Not closed system - daily intake of salt and water increases P_v while kidney excretion decreases P_a
• Can also say that cardiac output, Q is a function of (P_a-P_v)/R

Baroreceptor reflex 

(afferents, efferents and effectors)

• Carotid and aortic arch stretch-sensitive mechanoreceptors 
• Carotid sinus baroreceptors conveyed by CN IX, while aortic arch stretch receptors within CN X to the nucleus of the solitary tract, then to both parasympathetic and sympathetic neurons in brainstem
• NTS send glutamatergic fibres to caudal ventrolateral medulla (CVLM) which in turn sends GABAergic to the rostral ventrolateral medulla (RVLM), inhibiting it. The RVLM is the primary regultor of the sympathetic nerbous system via glutamatergic neurons projecting to the preganglionic sympathetic neurons within the spinal cord.
• Therefore, baroreceptor activation decreases sympathetic outflow, and in turn reduces blood pressure by reducing SVR.

• >140/90mmHg
• Increased systemic vascular resistance through the inrease in wall:lumen ratio of vessels to accomodate for a rise in cardiac output so that, when cardiac output returns to normal, the SVR remains increased
• An increased threshold of sodium excretion with regards to the arterial blood pressure

Tubuloglomerular feedback

(response to high BP and GFR)

• Renin - increased sodium chloride absorption increases sodium moving through the NKCC2 on apical membrane of macula densa cells, which in turn increases the activation of ATPases and conversion of ATP into ADP and AMP. 
• AMP can leave the basolateral membrane through stretch activated Maxi-Anion channels, and is converted to adenosine in the extracellular fluid by ecto-5'-nucleotidase. 
• Adensine then activates A₁ channels on extraglomerular mesangial cells, increasing calcium levels through the deactivation of adenylyl cyclase (G_i) and activation of PLC, IP3 and DAG through G₀.
• Increased intracellular calcium spreads to granular cells via gap junctions and inhibits renin release from juxtaglomerular cells

RAS pathway effects

(kidney and vasculature)

• Renin is converted from prorenin into renin by kallikrein 
• Renin converts angiotensinogen (from liver) into angiotensin I
• AG-I is converted to AG-II by ACE (in lungs)
• AG-II is a potent systemic vasoconstrictor, effects efferent arterioles of kidney to increase GFR, decreases medullary blood flow through vasa recta to reduce washout and increase sodium and water reabsorption, stimulates Na⁺/H⁺ exchanger to increase sodium reabsorption, and stimulates the release of aldosterone and ADH
• Aldosterone non-steroidal action to increase PKC and PKD within lumen epithelial cells, which stimulates variety of pumps and increases sodium reabsorption
• Steroidal aldosterone functions to upregulate and activate Na⁺/K⁺ basolateral ATPase, upregulates ENaC channels, increase Cl^- absorption to maintain electrochemical balance, stimulation of potassium secretion, stimulation of H⁺ATPase in intercalated cells, and upregulates expression of NCC
• Total effect to increase vascular tone and circulating volume in the face of low GFR and assumed blood pressure

Role of cortisol and adrenaline

(effects on renal function, vascular tone and circulating volume)

• Cortisol - thought that cortisol has a hypertensive effect by the inhibition of NO vasodilation, and therefore resulting in glucocorticoid hypertension
• Adrenaline - increase in vasoconstriction and cardiac output increases blood pressure, promotion of renal release to increase blood pressure through RAS system, some reduced renal perfusion leading to decreased sodium loss and therefore an increase in circulating volume

ADH effects

(kidney and vascular tone)

• AVPR2 - cAMP linked receptor - increased transcription and insertion of AQP2 into apical membrane of DCT and CD epithelial cells to allow movement of water out of nephron and back into the bloodstream 
• Increased permeability of inner medullary portion of the collecting duct to urea through expression of urea transporters, removing water from the lumen
• Increase in sodium reabsorption in ascending loop of Henle. 
• Action of V1 receptors to produce vasoconstrictor effect

Mechanisms of hypertension in Conn's and Cushing's syndrome

• Cushing's - excess cortisol potentiates the vasocontrictive effects of the sympathetic system (or ameloriates the vasodilatory effects of NO)
• Conn's syndrome - hyperaldosteronism leads to increased sodium retention and hypertension through abherrent and constitutive effects of aldosterone receptor activation

• Compliance is the increase in volume that occurs when the pressure is increased
• SVR is the resistance that must be overcome to push blood through the circulatory system and creat flow = 80x(mean arterial pressure - mean venous pressure)/cardiac output
• Mean circulatory pressure is the mean pressure that exists in the circulatory system when the blood is equally distributed to all vessels and organs (around 7mmHg)

Acute ventricular failure causes and signs

(left and right)

• Causes of acute failure - infection (infective endocarditis, allergic reaction, pulmonary embolism, arrythmia, myocardial infarction)
• Left sided failure causes pulmonary congestion - increased rate of breathing, crackles in lung bases, pumonary edema, cyanosis, displaced apex beat from LV hypertrophy, murmurs if caused by valve disease (aortic stenosis as cause, mitral regurgitation as symptom). 
• Right sided failure - usually by pulmoary hypertension or pulmoic stenosis. Presents with edema, liver enlargement and increases JVP

Features of shock

(types and signs)

• Hypovolaemic shock - loss of fluid leads to fall in CVP and therefore a reduction in cardiac output
• Presents with weakness, fatigue, thirst, cold skin, low P_a, low CVP, weak pulse, collapsed veins, confusion, tachcardia and acral sweating
• Responses to hypovolaemia - vasoconstriction of viscera and skin vessels (sympathetic) to increase MCP and thus CO and vital organ perfusion, sympathetic increased cardiac contractility through baroreceptor reflex, autotransfusion from ECM, increased breathing to elevate oxygen sats, EPO and ADH/RAS/adrenaline activation hormonally
• Cardiogenic shock - 40% loss of pump function, usually from MI (ruptured papillary muscles, ruptured septum, ventricular aneurysm, valve failure, ahrrythmia) - symptoms similar to hypovolaemic shock but CVP is high as the CO curve is lower, and may present with chest pain (infarct), breathnessless (high left atrial pressure), tachycardia, murmur, ECG changes (infarct)
• Septic - pathogen triggered loss of arteriolar tone (reduction in SVR) and increased permeability of capillaries to solutes and increased conductance of solvents (water), also linked to arteriovenous shunting. Reduction in arterial pressure as a result. 
• Presentation of measurements similar in all types of shock except - hypovolaemic shock sees a decrease in blood volume (others don't), cardiogenic shock sees a pronounced reduction in cardiac output and increase in central venous pressures (others drop) and septic shock sees resistance plummet (resistance increases in other)
• In all shock, the blood becomes acidotic