Kidneys Study Guide Week 7 PDF

Study Guide Kidneys (Week 7) NOTE – This study guide relates to the first two video playlists for Week 7. A separate study guide will be issued for the third playlist when it is released. A. Review the macroscopic and micr...

Study Guide Kidneys (Week 7) NOTE – This study guide relates to the first two video playlists for Week 7. A separate study guide will be issued for the third playlist when it is released. A. Review the macroscopic and microscopic structure of the kidneys B. Trace a drop of blood from the renal artery through the renal vein 1. Renal artery 2. Interlobar arteries 3. Arcuate arteries 4. Interlobular arteries 5. Afferent arterioles 6. Glomerulus 7. Efferent arterioles 8. Pertiubular capillaries 9. Interlobular vein 10. Arcuate vein 11. Interlobar vein 12. Renal vein C. Trace the path of filtrate from the glomerulus through the urethra 1. Bowman's capsule 2. Proximal tubule 3. Loop of henle i. Descending limb ii. Thin segment of ascending limb iii. Thick segment of ascending limb 4. Macula densa 5. Distal tubule 6. Connecting tubule 7. Collecting tubule 8. Collecting duct 9. Renal papillae 10. Renal pelvis 11. Ureter 12. Bladder 13. Urethra 14. NOTE – Items 1 through 6 above are all components of the nephron. By the time we get to the collecting ducts, that is no longer considered part of the nephron D. Describe the FOUR components to the renal processing of plasma within each nephron 1. Filtration i. As fluid passes from the afferent arteriole into the glomerulus, it is filtered in the glomerulus ii. This filtration is just like that in other capillaries (a) Plasma and everything dissolved in it is pushed through the capillary membrane (a) Electrolytes, glucose, various hormones, and drugs are filtered (b) Proteins and cells are too big to pass through, and therefore are not filtered  (b) The plasma that is filtered enters into Bowman’s capsule (a) This is the start of the renal tubular system (b) This fluid is now called “glomerular filtrate” iii. Remember, not all plasma passing through the glomerulus is filtered – some of it continues on to the effecter arterial, and from there, the peritubular capillaries 2. Reabsorption i. Some molecules in the glomerular filtrate get re-absorbed back into the bloodstream (a) This is similar to what happens in other capillaries in the body, where fluid that was filtered into the interstitium gets reabsorbed back into the venous end of the capillary (b) Reabsorption depends on multiple different factors (a) Transporters in the tubular cells. Some molecules have special transporters which allow them to move out of the tubule, through the tubular cell, and then into the capillary (b) Glucose is an excellent example of this. (i) In normal healthy circumstances, 100% of the glucose that is filtered through the glomerulus is reabsorbed back into the peritubular capillaries 1. This is why, under normal healthy conditions, there is no glucose in the urine (ii) In diabetes, when blood glucose levels are very high, the glucose transporters in the tubules get “saturated” (they are working at maximum capacity) 1. This allows some glucose to not get reabsorbed 2. Whatever glucose does not get reabsorbed winds up getting excreted in the urine 3. This is why diabetes is literally “sweet urine” (c) There are LOTS of other molecules which undergo reabsorption in the tubules, including (i) Sodium (ii) Calcium (iii) Bicarbonate (iv) Potassium (v) Many, many, more (d) The transporters vary in location throughout the tubular system (don’t get caught up in the details here) (i) in other words, the proximal tubular system has a different concentration of sodium transporters than the distal tubular system (e) Various hormones can control whether the transporters are turned “on” or “off” (i) This allows us to control just how much of a given molecule is reabsorbed (ii) Example: Aldosterone controls reabsorption of sodium 1. When blood pressure or plasma sodium levels are low, aldosterone is released, and aldosterone causes more sodium to be reabsorbed 2. When blood pressure or plasma sodium levels are high, aldosterone is not released, and less sodium is reabsorbed (so more is excreted) (c) Some molecules do not get reabsorbed at all (a) The best example of this is creatinine (not a typo – it is different than “creatine”) (i) Creatinine is a product of muscle phosphocreatine (PCr or CrP) metabolism (ii) Whatever creatinine is filtered through the glomerulus does NOT get reabsorbed 1. This means that ALL creatinine that is filtered gets EXCRETED  (iii) So, if blood creatinine levels being to rise, this typically means that we are not doing a good job filtering our plasma (i.e., kidney dysfunction) 3. Secretion i. Some molecules in the peritubular fluid are SECRETED back into the tubular system (a) In other words, molecules that were not filtered may be put back into the tubular system through this route (a) Note, some of these molecules may have already been filtered, but the ones that didn’t can now be secreted also (b) Example: (i) Hydrogen ions (H+) are filtered in the glomerulus, and get into the renal tubular system (ii) However, not all of the H+ passing through the glomerulus get filtered – some of them stay in the plasma and go on through the efferent arteriole and into the peritubular capillaries (iii) Some of those H+ that are in the peritubular capillaries will then get SECRETED into the tubular system. (iv) So, because of secretion, we wind up with more H+ in the tubular system than we started with (b) These molecules pass through the capillary, into the tubular cells, and then into the tubules. From there, they will get excreted (c) This involves similar mechanisms as for reabsorption in that secretion is: (a) Specific to certain molecules (b) Dependent on transporters (c) Can be controlled by various hormones (d) Some examples of molecules which are SECRETED include: (a) Hydrogen ions (b) Ammonia (c) Drugs (e.g. penicillin) 4. Excretion i. Whatever is left in the renal tubular system will pass into the collecting ducts, and eventually into the renal pelvis, the ureters, and the bladder, and ultimately be urinated out of the body ii. Is it just me, or is “excretion” much simpler than the other three? 😊😊 E. Water Balance and Thirst 1. Describe the role of plasma osmolarity in water balance i. Osmoreceptors in the brain (anterior hypothalamus) sense osmolarity of plasma (a) If osmolarity is high (high concentration of solutes), this suggests dehydration (b) If osmolarity is low (diluted solutes), this suggests overhydration (hyperhydration) ii. If osmolarity is high, anti-diuretic hormone is secreted form posterior pituitary (a) ADH = anti-diuretic hormone (a) Also known as vasopressin (b) Also known as arginine vasopressin (AVP) (b) ADH is an “anti-diuretic” – in other words, it is the opposite of a diuretic (a) That means ADH prevents water loss (c) ADH works by increasing the permeability of cells in the distal tubule and collecting ducts to water (a) This means water in the filtrate gets reabsorbed into the blood stream (b) So, with greater ADH secretion, more water gets reabsorbed into the bloodstream  (c) This results in more concentrated urine (and less urine also) iii. If osmolarity is high, this also increases thirst iv. If osmolarity is low, then the opposite of above happens (a) ADH is not released (a) This means less water is reabsorbed in the distal tubule and collecting ducts (b) This means a high volume of dilute urine is produced (b) Thirst is inhibited v. [Fun fact – alcohol inhibits the release of ADH, which why one has to urinate a lot after alcohol consumption]. F. Renal-Body Fluid System for Arterial Pressure Control 1. Differentiate between pressure diuresis and pressure natriuresis i. Pressure diuresis = As blood pressure increases urine output increases ii. Pressure natriuresis = As blood pressure increases sodium output increases G. Renin-Angiotensin System 1. Identify where renin is synthesized and stored i. Juxtaglomerular cells (JG cells) (a) In the walls of the afferent arterioles 2. Name the physiological stimulus which causes renin to be released i. Decreased arterial pressure in the afferent arterioles (a) Likely the case when systemic arterial blood pressure is reduced (b) Can also happen in renal ischemia 3. Briefly describe the function of renin i. Converts Angiotensinogen into Angiotensin I (a) Angiotensinogen is a precursor to angiotensin, which is made in the liver 4. Identify where Angiotensin I is converted to Angiotensin II, and name the enzyme which catalyzes this reaction (a) Mostly happens in the lung vasculature (a) Also in some other tissues including kidney and blood vessels (b) Enzyme = Angiotensin Converting Enzyme (ACE) 5. Rank the direct vasoactive effects of: renin, angiotensin I, angiotensin II i. [Least vasoactive] renin, angiotensin I, angiotensin II [most vasoactive = strongest vasoconstrictor] 6. Briefly describe the two key general mechanisms by which the renin-angiotensin system modulates blood pressure, including the relative timespan of each mechanism i. Vasoconstriction throughout body (rapid), generally in the arteries/arterioles (a) Increased arterial vasoconstriction (a) This means increased total peripheral resistance (b) This means Increased arterial blood pressure (b) Some vasoconstriction in the veins (a) This means increased venous return (b) This means increased end diastolic volume, which triggers the Frank-Starling mechanism (c) Increased stroke volume (d) Overcomes the afterload of the increased TPR ii. Decreased excretion of salt and water (works directly on kidneys) (slow – hours to days)  7. Briefly describe the how angiotensin II relates to aldosterone i. Angiotensin II causes adrenal glands to secrete aldosterone (a) Aldosterone Increases salt and water reabsorption 8. Explain how the renin-angiotensin system modulates blood pressure when salt intake is increased i. Increased extracellular fluid volume ii. Increased blood volume iii. Increased arterial pressure iv. Increased renal blood flow (a) Pressure diuresis (b) Pressure natriuresis v. Reduced renin (a) Reduced retention of sodium and water (b) Reduced blood volume (c) Reduced blood pressure 9. Describe the direct effects of a high sodium (salt) intake on arterial blood pressure i. Large changes in salt and water result in large changes in blood pressure (i.e., a large increase in sodium intake can create a large increase in arterial blood pressure) (a) This is because increased fluid intake leads to increased EXTRACELLULAR fluid – much of it stays in the vascular compartment (b) This means there is more plasma (water) in the veins (c) This means that pressure in the veins increases (d) This means that the pressure gradient between the veins and right atrium increases (e) This means venous return increased (f) This means the end diastolic volume (EDV) increases (g) This means greater cardiac contractility (h) This means greater Stroke Volume (SV) (i) With a greater stroke volume, that means a greater cardiac output – and a greater cardiac output means an increase in arterial blood pressure! (j) So, rapidly increasing our blood volume, by having a high salt intake with high fluid intake ultimately causes a short-term increase in our arterial blood pressure! ii. Chronic high sodium intakes results in very little change in blood pressure (in healthy individuals) (a) In other words, maintaining a high water or sodium intake will eventually lead to compensatory mechanisms (beyond the scope of this course) (b) So, over time, the body is not able to eliminate as much sodium and water (c) So, a chronic high salt diet will likely lead to chronically elevated arterial blood pressure H. Briefly describe how diuretic drugs help to lower blood pressure 1. If hypertension (high arterial blood pressure) is in part due to hypervolemia (fluid overload, due to high sodium levels), a diuretic will help eliminate fluid 2. Increased urine and/or sodium output i. This means a lower plasma volume ii. This means a reduced venous pressure iii. This means a reduced gradient between the veins and the right atrium  iv. This means reduced venous return v. This means reduced end diastolic volume vi. This means reduced stroke volume vii. And, that means a reduced cardiac output, which therefore lowers blood pressure! I. Integrated control of blood pressure 1. Identify the rapid, intermediate, and long-term mechanisms of blood pressure control i. Rapid (seconds to minutes) vasoconstriction or vasodilation, and increase/decrease in HR and contractility (a) Baroreceptor feedback ii. Intermediate (minutes beyond rapid mechanisms) (a) Renin-angiotensin system (b) Stress-relaxation of vasculature (we haven’t put much emphasis on this) (a) As blood vessels slowly stretch out, there is less pressure within them (c) Fluid shift between vascular and interstitial fluid (again, not much emphasis, but it does happen) (a) Fluid balance dependent upon Starling’s forces! iii. Long term (hours and beyond) (a) Renal-body control (a) Pressure diuresis (b) Pressure natriuresis (b) Aldosterone (a) Sodium reabsorption 2. Compare the sympathetic nervous systems response to increased versus decreased arterial pressure on diuresis and natriuresis i. Increased arterial blood pressure causes (a) Increased urine output (pressure diuresis) (b) Increased sodium output (pressure natriuresis) (a) Remember, water follows sodium (b) So, increased sodium removal should mean increased water removal (c) Decreased sympathetic nervous system activity (a) Hint, connect this to baroreceptors! (i) (High blood pressure is sensed, and leads to less sympathetic stimulation – which helps lower blood pressure) (d) Decreased renal-associated hormones (a) Angiotensin II (i) Less vasoconstriction, so lower TPR, so lower BP! (b) Aldosterone (i) Less sodium is reabsorbed, so less water is reabsorbed, so lower blood volume, so lower BP! ii. Conversely, decreased arterial blood pressure causes (a) Less urine output (b) Less sodium output (c) Increased sympathetic nervous system activity (a) Cardiac effects  (i) Increased HR (ii) Increased contractility (b) Vascular effect (i) Arterial vasoconstriction (ii) Venous vasoconstriction (d) Increased renal-associated hormones associated with maintaining fluid