IPHY 4440 1st Edition Lecture 19Outline of Last Lecture II. ZonationI. Other zonesIII. Glucocorticoid secretionIV. Types of action (of glucocorticoids)Outline of Current Lecture V. Mineralocorticoids VI. RAS (Renin-Angiotensin System)VII. Actions of A2I. RAS regulationII. Atrial Natriuretic PeptideIII. Clinical aspects of adrenal disorders Current LectureIV. MineralocorticoidsAldosterone is the major one A. Functions of aldosterone - Does something to the sodium/potassium balance- Potassium is kicked out in the presence of aldosterone- Water retained so more blood volume à hypertension (increase your blood pressure) - Aldosterone is a hypertensive hormoneB. Regulation of aldosterone secretion: RAS (renin-angiotensin system) and increased[K+]; Increased adrenal cortex, ACTH stimulates most of adrenal cortex but does not have an effect on RAS C. Involved 3 major organs in our body: Kidney, liver, lungs- When BP drops or you Na levels are too low, the kidney is activated- At the level of kidney: initiation site of RAS, releases protein called renin These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.V. RAS (Renin-Angiotensin System)A. Kidney releases renin (enzyme) that has a short half life in the blood meaning it will disappear in 15 min B. Renin release is stimulated by a drop in blood pressure or Na+C. Liver secretes a renin substrate called angiotensinogen which renin cleaves off 10aa to convert it to angiotensin-I aka A1D. Lung capillaries secrete a second enzyme called ACE à Angiotensin Converting EnzymeE. Summary of pathway: Angiotensin-I or A1 (ACE enzyme) à Angiotensin-II (8 AA)à A2 - A2 has a half life of 2 min and is also the most powerful hypertensive hormone in body How much AI gets into general circulation? (Arterial blood)- Very little, almost none becuase by the time the heart pumps it out its converted by ACE into A2- Will see A1 in veins and A2 in arteries - *Not biological very relevant: A1 not contributed to important organs VI. Actions of A2: all increase Blood Pressure (BP)1) Increases AVP release from Pars Nervosa: which in turn reabsorbs water, increases blood volume and increases blood pressure - AVP is a hypertensive hormone bc promotes water retention in body 2) Increase drinking: dipsogenic response (2nd way it raises blood pressure and blood volume)- It targets the brain and tricks brain into thinking that your thirsty then the organism will start to drink and drink 3) Increases arteriole smooth muscle which increases TPR which increases blood pressure as well (blood vessels are constricting)4) Increases aldosterone secretion: When sodium is reabsorbed by body, water follows and combined effects leads to increase in BP 5) Increases enzyme synthesis: aminopeptidase a which degrades A2 and promotes a protective negative feedback mechanism so angiotensin levels do not rise too much VII. RAS regulationA. JuxtaGlomerular Apparatus: JG cells that are modified cells of afferent arteriole that cause a drop in blood pressure which causes the release of renin - JG cells are the lining of the blood vessels that are slightly modified of afferent arteriole, but they can detect blood pressure change and have baroreceptors (BP change) B. Macula Densa: modified cells of distal tubule that detect a drop in Na+ which stimulates a positive effect on JG cells and releases renin from the JG stimulation - Line the distal tubule, cannot detect BP change but rather ion change (chemoreceptors), Cannot produce renin instead they make paracrine factors that will diffuse to the JG cellsto then tell them to release and make renin and triggers The RAS to increase BP C. Actions of potassium: high plasma [K+] has a direct effect on Z. glomerulosa which increases aldosterone release and increase in potassium excretion - In other words: Elevated potassium levels can directly stimulate Z. glomerulosa to release aldosterone and then can increase potassium excretion to lower potassium in blood D. Angiotensin-III : A2 (enzyme ACE2)à A3= A1-7 (ACE2 does not occur in lungs, primarily in heart and kidney; Takes one AA off and makes it A3 which has 7 aa)- A3 is a strong vasodilator and antihypertrophic: enlargement. Local control of vasodilation in kidney, heart, and smooth muscle and A3 is a way of counteracting A2- Prevents the normal growth of the heart that can lead to heart failure- Helps treat CVD- A2 most powerful vasoconstrictor and A3 is opposite VIII. Atrial Natriuretic PeptideProduced in the atrium of the heart Natriuretic: means hormone promotes sodium in urine so body excretes sodium 1) Induced by chronic high blood pressure2) Protects against high BPNatriuretic means Na+ in urine A. Targets for ANP: 1) Adrenal cortex à ANP inhibits aldosterone release à reduces Na+ reabsorption 2) Brain: ANP inhibits AVP release à causes diuresis 3) Kidney: ANP inhibits renin release à causes diuresis by decreasing A2 then decreaseAVP and decrease Aldosterone IX. Clinical aspects of adrenal disorders A. Cushing’s Syndrome: Increase GC’s and include both known and unknown causes- Syndrome means when we don’t know the cause of something;May or may not have known causes but just have a lot of GCsB. Cushing’s Disease (known cause): Pituitary adenomaà increase ACTH = Adrenal hyperplasia/hypertrophy, elevated GCs, Elevated adrenal androgens - This is a secondary causes, Crushing’s disease is always a secondary bc just responding to wrong signal but nothing wrong with adrenal glandC. Other causes of Crushing’s Syndrome: adrenal adenoma or carcinoma = GC synthesis à elecated GCs à Low ACTH- Crushing Syndrome can be classified as either secondary or