BSCI450: RAAS pH

RAS pathway stands for

renin-angiotensin system

RAS pathway mechanism

liver produces angiotensinogen -> renin -> angiotensin I -> ACE -> angiotensin II

what does renin do

cleaves angiotensinogen

what does ACE stand for

angiotensin converting enzyme

what does ANGII do in plasma

body wide vasoconstriction

integrated response (endocrine aldosterone + brain thirst/ADH)

arteriole constriction -> increased GFR

what is the overall function of angiotensin II

raise BP

what does angiotensin II response to

low GFR, low BP

3 mechanisms of renin production/activation

low BP -> low GFR -> low NaCl transport -> sensed by macula densa -> paracrine signalling -> granular cells of afferent arteriole -> renin

low BP -> CV control center -> increase sympathetic activity -> stimulate B1AR → granular cells of afferent arteriole -> renin

low BP -> piezo -> granular cells of afferent arteriole -> renin

how does piezo affect renin

high BP -> more piezo open -> inhibit renin

low BP -> less piezo open -> release renin

how does angiotensin II increase GFR

efferent constriction > afferent constriction

drugs that can treat hypertension

ACE blockers

angiotensin receptor antagonists

dieuretics

effect of angiotensin II via arterioles

body wide vasoconstriction -> increase BP

effect of angiotensin II via CV control center in medulla

increase CV response -> increase BP

effect of angiotensin II via hypothalamus

increase vasopressin & thirst -> increase volume and maintain osmolarity -> increase BP

effect of angiotensin II via adrenal cortex

increase aldosterone -> increase Na reabsorption -> increase volume and maintain osmolarity -> increase BP

effect of angiotensin II via proximal tubule

increase Na reabsorption -> increase volume and maintain osmolarity -> increase BP

what 5 areas does angiotensin II target

arterioles

CV control center in medulla

hypothalamus

adrenal cortex

proximal tubule

what do most anti-hypertensive treatments target

RAS system

RAAS pathway stands for

renin angiotensin aldosterone system

what does aldosterone do

promote Na⁺ reabsorption and K⁺ secretion

Two triggers for aldosterone release

low BP

hyperkalemia

how does low BP lead to aldosterone release (what pathway)

RAS pathway

how does hyperkalemia lead to aldosterone release

high K stimulates adrenal cortex -> aldosterone production -> aldosterone secretes excess K into tubule -> excreted via urine

what can K+ disrregulation lead to

cardiac arrhythmia

where are the adrenal glands

on top of kidney

what hormones are produced by adrenal cortex

aldosterone, glucocorticoids, sex hormones

what hormones are produced by adrenal medulla

catecholamines

what are all steroids derived from

cholesterol

what is true about connection of steroids

linked biosynthetic pathways

poorly functioning enzyme in one can lead to buildup of intermediate

what is the rate limiting step of aldeosterone synthesis

angiotensin II

how does angiotensin II regulate aldosterone production

upregulates 11-B-hydroxylase

what is the receptor of aldosterone

mineralocorticoid receptor (MR)

what kind of hormone is aldosterone

mineralocorticoid steroid

how to steroid hormones work

cross cell membrane -> bind nuclear receptor -> heat shock protein falls of NR -> NR now active -> forms dimer w/ other NR-hormone complex -> crosses through nuclear pore -> dimer binds genome -> affects transcription

lines of defense for maintaining body pH

bicarbonate levels

CO2 levels

what causes changes in pH

respiratory, metabolic

metabolic reasons for changes in pH

dietary acids, ketoacidosis, lactic acid

respiratory reasons for changes in pH

dissolved CO2

ketoacidosis

diabetics use fats and proteins to generate energy (since cells don’t have glucose)

what affects can pH have on neurons

neurons hypexcitable -> numbness, tingling, muscle twitches, tetanus

what part of tubule regulates HCO3

PCT

what does DCT regulate

H+ at the expense of K+ -> when one moves, so does the other

what structure exchanges H+ and K+ in DCT

H/K-ATPase

excrete H+ -> reabsorb K+

how does kidney regulate pH

bicarbonate levels