Kidney 2
RAAS activation 1) x themselves function as intrarenal baroreceptors. They are sensitive to pressure changes within the arteriole. When they detect a fall in pressure, they secrete renin 2) The x in the tubular portion of the juxtaglomerular apparatus are sensitive to NaCl moving past them through the tubular lumen. In response to a fall in NaCl, they trigger the granular cells to secrete renin. 3) x are innervated by the sympathetic nervous system. When BP falls below normal, the baroreceptors reflex increases sympathetic activity. As part of this response, increased sympathetic activity stimulates them secrete renin.
1) Granular cells themselves function as intrarenal baroreceptors. They are sensitive to pressure changes within the arteriole. When the granular cells detect a fall in pressure, they secrete renin 2) The macula densa cells in the tubular portion of the juxtaglomerular apparatus are sensitive to NaCl moving past them through the tubular lumen. In response to a fall in NaCl, the MD cells trigger the granular cells to secrete renin. 3) Granular cells are innervated by the sympathetic nervous system. When BP falls below normal, the baroreceptors reflex increases sympathetic activity. As part of this response, increased sympathetic activity stimulates the granular cells to secrete renin.
The two unregulated influences in glomerular filtration rate. Why?
1) Plasma colloidal osmotic pressure 2) Bowmans capsule hydrostatic pressure Both are unregulated and under normal conditions do not vary significantly.
***What are the 7 effects of ANP to reduce blood pressure?
1) Primary function of ANP is to directly inhibit Na+ reabsorption by the distal parts of the nephron increasing Na+ secretion in the urine. 2) Vasodilation of the afferent and vasoconstriction of the efferent arterioles of the glomerulus. This increases the GFR and filtered load of Na+. Relaxing the glomerular cells. All this leads to an increased Kf. 3) Inhibition of renin secretion by the juxtaglomerular cells. = reducing aldosterone secretion. 4) Inhibition of the aldosterone secretion by the adrenal cortex. 5) Inhibition of NaCl reabsorption by the collecting duct, which is also caused in part by lower levels of Aldosterone. However, the natriuretic peptides also act directly on the collecting ducts. 6) Inhibition of ADH secretion by the posterior pituitary and ADH action on the collecting duct. This decreases water reabsorption by the collecting duct and thus increases excretion of water in the urine. 7) Besides indirectly lowering BP by reducing the Na+ load and thus fluid load in the body, ANP also directly lowers BP by decreasing the cardiac output and reducing peripheral vascular resistance by means of inhibiting sympathetic nervous activity to the heart and blood vessels.
Glomerular hydrostatic pressure is determined by three variables
1) arterial pressure 2) afferent arteriolar pressure 3) efferent arteriolar pressure
Basic events of RAAS - and how angiotensin II and aldosterone work to correct original problem
1. Angiotensinogen is produced by liver - sent through blood. 2. Low NaCl/Low ECF volume/Low arterial blood pressure cause granular cells in kidney to secrete renin 3. Renin converts angiotensinogen into angiotensin I 4. Angiotensin converting enzyme made in lungs and sent through blood converts angiotensin I into angiotensin II 5. Angiotensin II stimulates adrenal cortex to produce aldosterone Aldosterone will cause reabsorption of Na+ in kidney distal tubules, and Cl- reabsorption follows passively - this will conserve Na+ and Cl- and cause H20 to be conserved in ECF. Angiotensin II, besides stimulating aldosterone production, will stimulate ADH, thirst, and arteriolar vasoconstriction. These will function to increase blood pressure through H20 reabsorption in kidney tubules (ADH), or increase fluid intake (thirst), or increase vasoconstriction to increase blood pressure
*****Name the ways GFR is controlled - via regulated mechanisms and unregulated mechanisms -this will definitely be an essay question
1. Controlled - Autoregulation via myogenic mechanism and tubuloglomerular feedback/ and Extrinsic sympathetic control controlled by baroreceptor reflex and sympathetic nervous system input 2. Unregulated - Plasma-colloid osmotic pressure Severely burned patient ↑ GFR Dehydrating diarrhea ↓ GFR Bowman's capsule hydrostatic pressure Obstructions such as kidney stone or an enlarged prostate can decrease filtration and elevate capsular hydrostatic pressure
Effects of dual control of aldosterone secretion of K+ and Na+?
1. K+ = Aldosterone responds to high blood K+, increases tubular secretion of K+, and thus increases urinary K+ excretion 2. Na+ = Aldosterone is the end product of the RAAS, which is activated by low Na+/low Blood pressure/ and low ECF volume. It promotes tubular Na+ reabsorption and thus decreases urinary Na+ excretion
***What are the 3 ways in which you can purposefully regulate the GFR? Main essay question
1. Myogenic mechanism - prevents short term flux - afferent arteriole contracts automatically when it is stretched due to increase in arterial driving pressure 2. Tubuloglomerular feedback - prevents short term flux - rate of fluid flow through nephron tubules stimulates macula densa to release vasoactive chemicals to control afferent arteriole 3. Sympathetic nervous system long term control - baroreceptor reflex that can detect low blood pressure and stimulate sympathetic nervous system for short term adjustments to increase cardiac output and total peripheral resistance by generalized arteriolar vasoconstriction, as well as long term from the effect of vasoconstriction of glomerular capillaries by mesangial cells to decrease GFR and thus cause less fluid and salt to be passed in urine - moving it back to blood to increase blood pressure. If the blood pressure is too high, the opposite response occurs - and sympathetic activity to arterioles is reduced allowing vasodilation to increase GFR.
***** Diagram the events that occur in RAAS - the Renin-angiotensin-aldosterone system. Definitely on exam
1. The kidneys secrete the enzymatic hormone renin in response to reduced NaCl, ECF volume, and arterial blood pressure. 2. Renin activates angiotensinogen, a plasma protein produced by the liver, into angiotensin I. 3. Angiotensin I is converted into angiotensin II by angiotensin-converting enzyme (ACE) produced in the lungs. 4. Angiotensin II stimulates the adrenal cortex to secrete the hormone aldosterone, which stimulates Na+ reabsorption by the kidneys. 5. The resulting retention of Na+ exerts an osmotic effect that holds more H2O in the ECF. Together, the conserved Na+ and H2O help correct the original stimuli that activated this hormonal system. Angiotensin II also exerts other effects that help rectify the original stimuli, such as by promoting arteriolar vasoconstriction.
In urine - detail which components occupy the larger fraction of composition?
1. urea = 200-400 mM 2. Na+ and Cl- = 50-130 mEq/L 3. K+ = 20-70 mEq/L
The total blood flow through the kidneys average x mL per minute, if the cardiac output is 5 liters, then this would be x % of the cardiac output Why is the blood flow to kidneys such a big chunk of cardiac output?
1140 mL per minute of blood flow through kidneys. If cardiac output is 5 liters, then this is 22% of cardiac output - a large portion The kidneys need to receive the large blood flow to monitor and control the ECF.
How is water reabsorbed in nephron? Are there different ways?
2 main ways - through the cell cytoplasm, or going between cells 1. Passive transport of H20 from lumen of tubule to enter cytoplasm through Aquaporin-1 water channels, and passively diffuse to interstitial fluid through Aquaporin-1 water channels, then across IF to enter peritubular capillaries 2. H20 enters between tubular cells and goes straight to IF and then crosses to peritubular capillary
The kidneys receive x% percent of the cardiac output
20-25%
What parts of heart secrete ANP and BNP? How are they stored in the heart? What is their effect?
ANP - Atria BNP - ventricles ANP and BNP are stored in granules in the heart and released when the heart muscle cells are mechanically stretched by an expansion of the circulating plasma volume. NPs promote natriuresis and accompnaying diuresis, decreasing the plasma volume and also influence the cardiavascular system to lower blood pressure.
***How does ANP work to lower blood pressure and counteract the RAAS?
ANP will try to lower blood pressure when there is high NaCl, high ECF, high blood pressure by 1. Decreasing Na+ reabsorption by kidney tubules 2. Inhibiting RAAS 3. Causing vasodilation of afferent arterioles to glomerulus - increasing GFR and causing more Na+ and H2O to be filtered to urine 4. Inhibiting sympathetic nervous system - thus decreasing cardiac output and total peripheral resistance and decreasing blood pressure
Increases Na+ reabsorption by the distal convoluted tubules
Aldosterone
Okay, so we know Aldosterone increases Na+ reabsorption from the kidneys, but what inhibits Na+ reabsorption?
Atrial Natriuretic peptide RAAS is the Na retaining, blood pressure raising system. Atrial Natriuretic Peptide (ANP) opposes RAAS by a Na losing, blood pressure lowering system that involves ANP and Brain natriuretic peptide (BNP). The heart produces both ANP and BNP.
***What is the baroreceptor reflex? Why is it important for GFR? This will be a monkey memorization essay question
Baroreceptor reflex influences the GFR via long term regulation of arterial blood pressure 1. Higher arterial blood pressure triggers both long term and short term changes to lower blood pressure. 2. High blood pressure sensed in aortic arch and carotid sinus baroreceptors 3. These release vasoactive chemicals that increase sympathetic activity and promote generalized arteriolar constriction such as ATP, endothelin/ADH/vasopressin, and adenosine 4. The increased sympathetic activity increases cardiac output 5. Increased sympathetic activity also increases general vasoconstriction - leading to higher total peripheral resistance and afferent arteriolar vasoconstriction 6. Thus, glomerular capillary blood pressure goes down, 7. GFR down 8. Urine volume down 9. More salt and fluid are conserved 10. These go back to increase blood pressure Thus, low blood pressure promotes long and short term adjustment. Short term is the increased sympathetic activity and vasoconstriction effects to increase cardiac output and total peripheral resistance. Long term is the vasoconstriction of afferent arterioles to glomerulus, lowering GFR, lowering urine volume and retaining fluid and salt to increase blood pressure.
Effects of constriction and dilation on efferent/afferent arterioles and how this would affect GFR
Constriction of the afferent arteriole decreases Pgc as less arterial pressure is transmitted to the glomerulus Dilation of afferent arteriole increases Pgc, because more arterial pressure is transmitted to the glomerulus. Constriction of the efferent arteriole increases Pgc and thus increases GFR ( mild constriction causes increase and stronger constriction causes decrease) Dilation of the efferent arteriole increases Pgc because more of the arteriole pressure is transmitted to the glomerulus.
Decreased pressure tends to lower/increase glomerular hydrostatic pressure while Increased pressure tends to raise/lower glomerular hydrostatic pressure
Decreased pressure tends to lower glomerular hydrostatic pressure Increased pressure tends to raise glomerular hydrostatic pressure
What's the importance of mesangial cells? How do they influence the glomerular capillaries to decrease or increase GFR?
Each tuft of capillaries is held together by a mesangial cells. These cells contain contractile elements (actin like elements). Contraction of these mesangial cells closes off a portion of the filtering capillaries, reducing the surface area available for filtration within the glomerulus. When the net filtration pressure remains unchanged, this reduction in Kf decreases the GFR. Sympathetic stimulation causes the mesangial cells to contract, providing a second mehanism (besides promoting afferent arteriolar vasconstriction.
***When the body signals for increased sympathetic activity - how exactly is this going to affect the GFR? What two things are changing to affect the GFR? What are the cells controlling these two things
Each tuft of glomerular capillaries is held together by a mesangial cells. These cells contain contractile elements (actin like elements). Contraction of these mesangial cells closes off a portion of the filtering capillaries, reducing the surface area available for filtration within the glomerulus. When the net filtration pressure remains unchanged, this reduction in Kf decreases the GFR. Sympathetic stimulation causes the mesangial cells to contract, providing a second mechanism (besides promoting afferent arteriolar vasconstriction. So, the body regulates the afferent arterioles to control blood pressure with the intrinsic autoregulatory tubuloglomerular control, while the body can affect contractile mesangial cells' effects on glomerular capillaries to reduce or increase Kf and thus GFR - this is the extrinsic sympathetic reflex and uses sympathetic activity to contract mesangial cells.
Constriction of the afferent arteriole decreases x as less arterial pressure is transmitted to the glomerulus Dilation of afferent arteriole increases x, because more arterial pressure is transmitted to the glomerulus.
Glomerular capillary pressure
***How is the Renin-angiotensin-aldosterone system activated? The basic mechanism and the three ways to do it
Granular cells of Macula densa secrete Renin into the blood in response to a fall in NaCl/ECF volume/blood pressure. This is caused via 3 methods. 1. LOW BLOOD PRESSURE - Granular cells themselves function as intrarenal baroreceptors and will secrete renin when they sense a fall in pressure 2. LOW NaCl - Macula densa cells in tubular portion of juxtaglomerular apparatus sense NaCl concentrations. When NaCl is low, Macula densa cells trigger granular cells to secrete renin 3. INCREASED SYMPATHETIC ACTIVITY - Granular cells are innervated by the sympathetic nervous system, which is triggered by aortic and carotid baroreceptors responding to low BP. This sympathetic stimulation causes granular cells to secrete renin.
Atrial Natriuretic Peptide (ANP) 1. Inhibits x reabsorption 2. Secreted by atria in response to 3. Release promotes x effects to help correct the original stimulus that brought about release of ANP 4. The main function of ANP is to x
Inhibits Na+ reabsorption Secreted by atria in response to being stretched by Na+ retention, expansion of ECF volume, and increase in arterial pressure Release promotes natriuretic, diuretic, and hypotensive effects to help correct the original stimulus that brought about release of ANP The main function of ANP is to directly inhibit Na+ reabsorption in the distal part of the nephron
Tubular reabsorption 1. What is it? 2. Selective? 3. Involves x transport 4. Reabsorbed substances must cross how many barriers? 5. What are these barriers?
Involves the transfer of substances from tubular lumen into peritubular capillaries Highly selective and variable process Involves transepithelial transport Reabsorbed substance must cross five barriers Must leave tubular fluid by crossing luminal membrane of tubular cell Must pass through cytosol from one side of tubular cell to the other Must cross basolateral membrane of the tubular cell to enter interstitial fluid Must diffuse through interstitial fluid Must penetrate capillary wall to enter blood plasma
Name the two unregulated influences on the GFR on how they can change with body disturbances?
Pathologically plasma-colloid osmotic pressure and Bowman's capsule hydrostatic pressure can change Plasma-colloid osmotic pressure Severely burned patient ↑ GFR Dehydrating diarrhea ↓ GFR Bowman's capsule hydrostatic pressure Obstructions such as kidney stone or an enlarged prostate can decrease filtration and elevate capsular hydrostatic pressure
Primary function of x is to directly inhibit Na+ reabsorption by the distal parts of the nephron increasing Na+ secretion in the urine.
Primary function of ANP is to directly inhibit Na+ reabsorption by the distal parts of the nephron increasing Na+ secretion in the urine.
Macula densa cells - besides having a role in autoregulation, have a function in
RAAS
*** If you want to increase blood pressure - you choose this system If you want to decrease blood pressure - you choose this system.
RAAS is the Na retaining, blood pressure raising system. Atrial Natriuretic Peptide (ANP) opposes RAAS by a Na losing, blood pressure lowering system that involves ANP and Brain natriuretic peptide (BNP). The heart produces both ANP and BNP.
Function of atrial natriuretic peptide
RAAS is the Na retaining, blood pressure raising system. Atrial Natriuretic Peptide (ANP) opposes RAAS by a Na losing, blood pressure lowering system that involves ANP and Brain natriuretic peptide (BNP). The heart produces both ANP and BNP.
What is the RAAS and its main function?
Renin-angiotensin-aldosterone system, most import and best known hormonal system involved in regulating Na+ Aldosterone increases Na+ reabsorption by the distal convoluted tubules
Myogenic Mechanism
Responds to pressure changes in the nephron between 90 and 180mm.Hg. Arteriolar vascular smooth muscle contracts automatically in response to the stretch caused by increased pressure within the vessel. So afferent arteriole contracts automatically when it is stretched due to increase in arterial driving pressure. Conversely, inherent relaxations of an unstretched afferent arteriole when pressure is reduced will increase the blood flow into the glomerulus in spite of the reduced arterial driving pressure.
What's the filtration coefficient and why is it important to GFR?
The GFR is influenced by changes in the filtration coefficient This coefficient is not constant but is subject to physiological control. The coefficient depends on surface area and the permeability of the glomerular membranes. Both can be modified by contractile activity within the membrane.
Juxtaglomerular apparatus
The juxtaglomerular apparatus consists of specialized vascular cells (the granular cells) and specialized tubular cells (the macula densa) at a point where the distal tubule passes through the fork formed by the afferent and efferent arterioles of the same nephron.
What's the juxtaglomerular apparatus?
The juxtaglomerular apparatus consists of specialized vascular cells (the granular cells) and specialized tubular cells (the macula densa) at a point where the distal tubule passes through the fork formed by the afferent and efferent arterioles of the same nephron.
*****What's the tubuloglomerular feedback mechanism of autoregulation? What's its purpose? This will be a monkey memorization essay question
The kidney tubules will respond to the amount of fluid flow through them, which is caused by blood pressure in GFR. So, this is a feedback mechanism designed to keep the GFR maintained. It occurs in BOTH DIRECTIONS HERE WHEN BLOOD PRESSURE IS HIGHER 1. Arterial blood pressure goes up 2. Causes increased pressure into glomerulus 3. Thus, glomerular capillary pressure up. 4. Glomerular filtration rate up 5. More fluid flow through kidney tubules 6. This fluid flow stimulates macula densa cells to release vasoconstriction chemicals such as ATP, adenosine, endothelin/vasopressin 7. Chemicals released to induce afferent arteriolar vasoconstriction 8. Blood flow into glomerulus goes down 9. Glomerular capillary pressure goes down 10. Glomerular filtration rate to normal WHEN BLOOD PRESSURE IS LOW 1. Arterial blood pressure is low 2. Decreases pressure into glomerulus 3. Glomerular capillary pressure down 4. GFR down 5. Rate of fluid flow through kidney tubules down 6. Stimulation of macula densa cells to release vasodilators such as NO, prostaglandins, bradkykinins 7. afferent arteriolar vasodilation 8. blood flow into glomerulus up 9. glomerular capillary pressure returns to normal 10. GFR back to normal
How can glomerular capillary blood pressure be controlled to adjust GFR for body needs?
Two major control mechanisms Autoregulation (aimed at preventing spontaneous changes in GFR) Myogenic mechanism Tubuloglomerular feedback (TGF) Extrinsic sympathetic control (aimed at long-term regulation of arterial blood pressure) Mediated by sympathetic nervous system input to afferent arterioles Baroreceptor reflex
Two major mechanisms for controlling glomerular capillary blood pressure
Two major mechanisms for control: Autoregulation: (intrinsic) short term regulation that prevents spontaneous changes in GFR. Extrinsic sympathetic control: used for long-term regulation of arterial blood pressure.
Where are atrial and brain natriuretic peptide produced?
both in the heart.
Baro-receptor reflex is what type of control on GFR?
extrinsic sympathetic control
The x can be controlled to adjust the GFR
glomerular capillary blood pressure
What are the four substances that are never excreted in urine in a normal individual?
glucose, phenol, amino acids, bilirubin
Which cells secrete renin?
granular cells
Conversely, inherent relaxations of an unstretched afferent arteriole when pressure is reduced will increase/decrease the blood flow into the glomerulus in spite of the reduced arterial driving pressure.
increase
Mean arterial blood pressure is 80-180mm Hg. Normal mean arterial pressure is 93 mmHg So, within the normal range of arterial blood pressure, intrinsic autoregulatory adjustments of afferent arteriolar resistance can compensate for changes in arterial pressure thus preventing x even though glomerular pressure tends to change in the same direction as arterial pressures.
preventing inappropriate fluctuations in GFR
Filtration coefficient depends on
surface area and the permeability of the glomerular membranes.
In addition to the intrinsic autoregulatory control, the GFR can be changed even when the mean arterial blood pressure is within the auto-regulatory range via
the baroreceptor reflex
Arteriolar vascular smooth muscle contracts automatically in response to the x So afferent arteriole contracts automatically when it is stretched due to increase in arterial driving pressure.
the stretch caused by increased pressure within the vessel.
What is the purpose of RAAS?
to increase blood pressure and/or NaCl in the blood. Uses aldosterone to help reabsorb Na+. Renin secretion by granular cells starts the process.
Out of these- water, Na+, K+, urea, chloride and calcium - which is excreted as much as it is reabsorbed?
urea
