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Renal Physiology Cheat Sheet by

Subject- Physiology: Life Sustaining Systems Source- Principles of Anatomy and Physiology by Tortora

The Nephron

Nephron is the functional unit of the kidney.
Each nephron consists of two parts:
1. Renal Corpuscle: filters the blood plasma. It consists of two compon­ents: glomerular capill­aries and glomerular (Bowman's) capsule.
2. Renal Tubules: into which the filtered fluid passes. Consists of Proximal Convoluted Tubule, Loop of Henle, Distal Convoluted Tubules. Loop of Henle has an ascending limb and a descending limb.
80-85% nephrons are cortical nephrons. Their corpuscles are in the cortex and they have short loop of Henle that receives blood supply from peritu­bular capill­aries of efferent arteri­oles.
15-20% nephrons are juxtam­edu­llary nephrons, which have corpuscles deep in the cortex and long loop of Henle that extends into the medulla. Long loops of Henle receive blood supply from peritu­bular capill­aries and vasa recta that arise from efferent arteri­oles.

Figure:

The structure of nephrons and associated blood vessels.

Renal Physiology

Nephrons and collecting ducts perform three basic process for urine formation:
1. Glomerular Filter­ation: water and most solutes in the blood plasma move across the wall of glomerular capill­aries into the glomerular capsule and then into renal tubule.
2. Tubular Reabso­rption: As filtered fluid passes down the renal tubule and through the collecting duct, tubule cells reabsorb 99% of the filtered water and many useful solutes. The water and solutes return to the blood as it flows through the peritu­bular capill­aries and vasa recta.
3. Tubular Secretion: As the fluid flows through the renal tubule and collecting ducts, the tubule and ducts secrete other materials, such as wastes, drugs and excess ions, into the fluid.

Figure:

Relation of a nephron’s structure to its three basic functions: glomerular filtra­tion, tubular reabso­rption, and tubular secretion

Figure:

Tubulo­glo­merular feedback.

Figure:

Reabso­rption routes: parace­llular reabso­rption and transc­ellular reabso­rption

Figure:

Reabso­rption of glucose by Na+-glucose symporters in cells of the proximal convoluted tubule (PCT).

Figure:

Actions of Na+/ H+ antipo­rters in proximal convoluted tubule cells. (a) Reabso­rption of sodium ions (Na+) and secretion of hydrogen ions (H+) via secondary active transport through the apical membrane; (b) reabso­rption of bicarb­onate ions (HCO3-) via facili­tated diffusion through the basola­teral membrane. CO2 = carbon dioxide; H2CO3 = carbonic acid; CA = carbonic anhydrase.

Figure:

Passive reabso­rption of Cl-, K+, Ca2+, Mg2+, urea, and water in the second half of the proximal convoluted tubule.

Hormonal Regulation

Renin-­Ang­iot­ens­in-­Ald­ost­erone System
When blood volume and blood pressure decrease, walls of the afferent arterioles are stretched less and Juxtag­lom­erular apparatus secretes renin.
Renin clips of angiot­ensin I (10 amino acid peptide) from angiot­ens­inogen (synth­esised by hepato­cytes). Angiot­ensin converting enzyme clips off two more amino acids from angiot­ensin I and forms angiot­ensin II
Angiot­ens­inogen --renin--> angiot­ensin I --ACE--> angiot­ensin II
Angiot­ensin II decreases GFR, enhances Na+ and Cl- reabso­rption in PCT and stimulates adrenal cortex to release aldost­erone. Aldost­erone stimulates principal cells in collecting ducts to reabsorb more Na + and Cl-.
Antidi­uretic Hormone
Released by pituitary gland, it regulates facult­ative water reabso­rption by increasing the water permea­bility of the prinicpal cells in the DCT and collecting duct.
Within principal cells are tiny vesicles containing many copies of a water channel protein known as aquapo­rin-2. ADH stimulates insertion of the aquapo­rin­-2–­con­taining vesicles into the apical membranes via exocyt­osis.
When the osmolarity or osmotic pressure of plasma and inters­titial fluid increa­ses­—that is, when water concen­tration decrea­ses—by as little as 1%, os- morece­ptors in the hypoth­alamus detect the change. Their nerve impulses stimulate secretion of more ADH into the blood, and the principal cells become more permeable to water. As faculta- tive water reabso­rption increases, plasma osmolarity decreases to normal.
Atrial Natriu­retic Peptide
A large increase in blood volume promotes release of atrial natriu­retic peptide (ANP) from the heart. It can inhibit reabso­rption of Na+ and water in the proximal convoluted tubule and collecting duct. ANP also suppresses the secre- tion of aldost­erone and ADH.
These effects increase the excre- tion of Na􏱩 in urine (natri­uresis) and increase urine output (diure­sis), which decreases blood volume and blood pressure.
Parath­yroid Hormone
A lower-­tha­n-n­ormal level of Ca2+ in the blood stimulates the parath­yroid glands to release parath­yroid hormone (PTH). PTH in turn stimulates cells in the early distal convoluted tubules to reabsorb more Ca2+ into the blood.

Figure:

Formation of dilute urine.

Figure:

Mechanism of urine concen­tration in long-loop juxtam­edu­llary nephrons.
 

Glomerular Filter­ation

Fluid that enters capsular space- Glomerular Filtrate
The fraction of blood plasma in the afferent arterioles of the kidney that becomes glomerular filtrate- filtration factors
The Filtration Membrane:
Endoth­elial cells of the glomerular capill­aries and the podocytes (which completely encircle the capill­aries) form a leaky barrier know as the Filtration Membrane. This assembly permits filtration of water and solutes but prevents filtration of plasma proteins, platelets and blood cells.
Substances filtered from the blood cross three barriers- glomerular endoth­elial cell, basal lamina and filtration slit formed by podocyte.
1. Glomerular endoth­elial cells are leaky because they have large fenest­rat­ions. Located among the glomerular capill­aries and in the cleft between the afferent and efferent arterioles are the mesangial cells. These contra­ctile cells help regulate glomerular filtration rate.
2. the basal lamina is a layer of acellular material between the endoth­elium and the podocytes, consisting of collage fibres and proteo­glycans in a glycop­rotein matrix. It prevents filtration of large plasma proteins.
3. Extending from each podocyte and thousands of footlike projec­tions termed pedicels which wrap around glomerular capill­aries. The spaces between pedicels are the filtration slits. A thin membrane extends across the slits called the filtration membrane that permits the passage of smaller molecules such as water, glucose, vitamins, amino acids, ammonia, urea and ions.
Volume of fluid filtered by the glomerular capill­aries is much larger than in other capill­aries of the body because:
1. Glomerular capill­aries present a large surface area for filtration because they are long and extensive. When mesangial cells are relaxed, the surface area is maximal and the glomerular filtration is very high. Contra­ction of mesangial cells reduces the available surface area, and the glomerular filtration decreases.
2. The filtration membrane is thin and porous. Glomerular capill­aries are about 50 times leakier than regular capill­aries.
3. Glomerular capillary blood pressure is higher than in capill­aries elsewhere in the body because the efferent arteri­ole's diameter is much smaller than the afferent arteri­ole's diameter. Hence, resistance to outflow of blood from the glomerulus is high.
Net Filtration Pressure:
Glomerular filtration depends of three main pressures:
1. Glomerular Blood Hydros­tatic Pressure: blood pressure in the glomerular capill­aries. It is about 55mmHg and promotes filtration by forcing water and solutes in the blood plasma through the filtration membrane.
2. Capsular Hydros­tatic Pressure: hydros­tatic pressure exerted against the filtration membrane by the fluid already in the capsular space and renal tubule. It opposes filtration and exerts a pressure of 15mmHg.
3. Blood Colloid Osmotic Pressure: due to presence of proteins such as albumins, globulins, and fibrinogen in blood plasma opposes filtra­tion. It is about 30 mmHg.
Net filtration pressure: (GBHP-­CHP­-BCOP) = (55-15-30) =10mmHg.
Glomerular Filtration Rate:
The amount of filtrate formed in all the renal corpuscles of both kidneys in a minute, is the Glomerular Filtration Rate. Average GFR of males- 125 ml/min and of females- 105 ml/min.
Any change in net filtration pressure affects GFR. Filtration ceases if the GBHP drop to 45mmHg.
Three mechanisms control GFR:
1. Renal Autore­gul­ation: ability of the kidneys to help maintain a constant blood flow and GFR despite changes in blood pressure. Renal autore­gul­ation consists of two mechan­isms: myogenic mechanism and tubulo­glo­merular feedback.
~ Myogenic Mechanism occurs when stretching of afferent arteriole due to elevated blood pressure triggers the smooth muscle fibres in the wall to contract, which narrows the arteri­ole's lumen, thereby decreasing renal blood flow and restoring GFR.
~Tubulo­glo­merular Feedback occurs when the macula densa detect increased density of Na+ and Cl- ions as they are not being reabsorbed by the Loop of Henle. The macula densa inhibits release of NO from the Juxtag­lom­erular apparatus, causing arterioles to contract and restoring GFR.
2. Neural Regula­tion: blood vessels of kidney are supplied by sympat­hetic ANS fibres that release norepi­nep­hrine. Norepi­nep­hrine causes vasoco­nst­riction through activation of alpha 1 receptors, which are plentiful in smooth muscle fibres of afferent arteri­oles. With great sympat­hetic stimul­ation, blood flow into the glomerular capill­aries is decreases and GFR drops. This reduces urine output, which helps conserve blood volume and it permits greater blood flow to other body tissues.
3. Hormonal Regula­tion: Hormonal regulation of GFR is done by Angiot­ensin II and Atrial Natriu­retic Peptide. Angiot­ensin II is a vasoco­nst­rictor that narrows both efferent and afferent arterioles and reduces renal blood flow, thereby reducing GFR. Atrial Natriu­retic Peptide is secreted by cells in atria of heart when the atria is stretched due to increase in blood volume and causes relaxation of the glomerular mesangial cells, increasing capillary surface area and increasing GFR.

Tubular Secretion and Tubular Reabso­rption

Tubular Reabso­rption: the return of filtered water and many of the filtered solutes back to the blood stream.
Epithelia cells along renal tubule and duct and PCT cells carry out reabso­rption.
Tubular Secretion: transfer of materials from the blood and tubule cells into the tubular fluid.
Reabso­rption routes
1. Parace­llular Reabso­rption: Reabso­rption of fluid through between the cells in a passive process.
2. Transc­ellular Reabso­rption: Reabso­rption of fluid through the apical membrane, cytosol ad basola­teral membrane of a tubule cell.
Transport Mechanisms
Primary Active Transport: Energy derived from hydrolysis of ATP is used to pump a substance across a membrane. Eg. Na+/K+ ATPase.
Secondary Actie Transport: Energy stored in an ion's electr­och­emical gradient drives another substance across the membrane.
Sympor­ters: membrane proteins that move two or more substances across a membrane in the same direction.
Antipo­rters: membrane proteins that move two or more substances across a membrane in opposite direct­ions.
Transport Maximum (Tm): maximum rate at which a system is able to transport a solute.
Obligatory Water Reabso­rption: Solute reabso­rption drives water reabso­rption because all water reabso­rption occurs via osmosis and water is obliged to follow the solutes when they are reabso­rbed. Occurs in PCT and descending loop of Henle
Facult­ative Water Reabso­rption: Reabso­rption regulated by antidi­uretic hormone. Occurs in the collecting ducts.
Reabso­rption and Secretion in PCT
Solute reabso­rption in the proximal convoluted tubules involves Na+. Na+ transport occurs via symporters and antipo­rters.
Filtered glucose, amino acids, lactic acid, water soluble vitamins and other nutrients are completely reabsorbed by several types of Na+ symporters located in the apical membrane.
Na+/ H+ antipo­rters carry filtered Na+ down its concen­tration gradient into a PCT cell as H+ is moved from cytosol into the lumen, causing Na+ to be reabsorbed into the blood and H+ to be secreted into the tubular fluid.
PCT cells produce H+ by dissoc­iation of Carbonic Acid into H+ and HCO3-.
Solute reabso­rption in PCT promotes water reabso­rption by osmosis. Reabso­rption of solutes creates a concen­tration gradient that promotes osmosis.
Cells lining the PCT and descending loop of Henle are more permeable to water because they have molecules of aquapo­rin-1 (integral protein in plasma membrane that forms a water channel, increasing the rate of water movement across the apical and basola­teral membrane).
In the second half of PCT, electr­och­emical gradients for Cl-, K+, Mg2+, Ca2+ and urea promote their passive diffusion into peritu­bular capill­aries.
Diffusion of Cl- ions into inters­titial fluid via parace­llular route makes the inters­titial fluid more negative than the tubular fluid. This negativity promotes movement of positive ions such as K+, Mg2+, Ca2+.
Ammonia is a poisonous waste product derived from the deamin­ation of various amino acids, a reaction occuring in hepato­cytes.
Hepato­cytes convert ammonia into urea. Urea and ammonia in blood are both filtered at the glomerulus and secreted by proximal convoluted tubule cells into the tubular fluid.
Reabso­rption and Secretion in Loop of Henle
Loop of Henle reabsorbs 15% water, 20-23% sodium and calcium, 35% Chlorine, 10-20% HCO3-
Ascending limb of the Loop of Henle is relatively imperm­eable to water.
Apical membrane of thick ascending loop of Henle have Na+-K+-Cl- sympor­ters. Na+ is actovely transp­orted into inters­titial fluid and diffuses into vasa recta. Cl- moves through leakage channels into inters­titial fluid and then into vasa recta. K+ ions that are brought in by symporters move down the concen­tration gradient back into tubular fluid.
Movement of positively charged K into the tubular fluid leaves a relative negativity in the inters­titial fluid, which promotes reabso­rption of cations like sodium, calcium, magnesium.
Reabso­rption and Secretion in DCT
Early or initial part of DCT reabsorbs 10-15% filtered water, 5% Na and 5% Cl. Reabso­rption of Na and Cl happens through Na+/Cl- sympor­ters.
Early DCT is a major site where parath­yroid hormone stimulates reabso­rption of Ca2+.
In late DCT, two types of cells are present: principle cells and interc­alated cell
Principle cells reabsorb Na+ and secrete K+. Interc­alated cells reabsorb K+ and HCO3- and secrete H+.

Figure:

Na+–K+–2Cl- symporter in the thick ascending limb of the loop of Henle.

Figure:

Reabso­rption of Na+ and secretion of K+ by principal cells in the last part of the distal convoluted tubule and in the collecting duct.

Formation of Dilute Urine

When dilute urine is formed, osmolarity of he tubular fluid increases as it flows down the descending loop of Henle, increases as it flows up the ascending limb and decreases more as it flows through the rest of the nephron and collecting ducts.
1. Osmolarity of the inters­titial fluid of the medulla becomes progre­ssively greater, more and more water is reabsorbed by osmosis as tubular fluid moves along descending limb of loop of Henle. Hence, fluid in the lumen becomes more and more concen­trated.
2. Cells lining the thick ascending loop will have symporters that actively reabsorb Na, K and Cl from the tubular fluid.
3. Although solutes are being reabsorbed in the thick ascending limb, the water permea­bility is quite low
4. While fluid flows along DCT, additional solutes but very few water molecules are absorbed.
5. Principle cells in the DCT and collecting ducts are imperm­eable to water when ADH levels are low. Thus tubular fluid becomes for diluted as it flows onwards.
osmolarity of tubular fluid increa­ses­=water concen­tration decreases

Formation of Concen­trated Urine

When water intake is low, or water loss is high, the kidneys are capable of producing small amount of highly concen­trated urine under the influence of ADH in order to conserve water.
Ability of ADH to cause excretion of concen­trated urine depends on the presence of an osmotic gradient of solutes in the inters­titial fluid of medulla.
Two main factors contribute to building and mainta­ining the osmotic gradient in the renal medulla:
1. difference in solute and water permea­bility and reabso­rption in different sections of the long loops of Henle and collecting ducts.
2. counte­rcu­rrent flow of the flow of fluid through the tube shaped structures in the renal medulla.
Counter current flow refers to the flow of fluid in opposite direct­ions.
Counte­rcu­rrent Multip­lic­ation
Counte­rcu­rrent multip­lic­ation is the process by which a progre­ssively increasing osmotic gradient is formed in the inters­titial fluid of the renal medulla as a result of counte­rcu­rrent flow.
Production of concen­trated urine in the kidneys occurs in the following way:
1. Symporters in the thick ascending limb of the loop of Henle cause a buildup of Na+ and Cl- in the renal medulla. Water is not reabsorbed in this section as it is imperm­eable to water.
2. Counte­rcu­rrent flow through the descending and ascending limbs of loop of Henle establ­ishes an osmotic gradient in the renal medulla.
3. Cells in the collecting ducts reabsorb more water and urea with increase in ADH. With loss of water, urea left behind in the collecting ducts becomes increa­singly concen­trated and diffuses from the fluid in the duct into the inters­titial fluid of the medulla.
4. Urea recycling causes buildup of urea in the renal medulla. As urea accumu­lates in the inters­titial fluid, some of it diffuses into the tubular fluid in the descending and thin ascending limbs of the long loops of Henle. However, while the fluid flows through the thick ascending limb, distal convoluted tubule, and cortical portion of the collecting duct, urea remains in the lumen because cells in these segments are imperm­eable to it.
Constant transfer of urea between segments of the renal tubule and inters­titial fluid is termed urea recycling.
Counte­rcu­rrent Exchange
Counte­rcu­rrent exchange is the process by which solutes and water are passively exchanged between the blood of the vasa recta and inters­titial fluid of the renal medulla.
Counte­rcu­rrent flow between the descending and the ascending limbs of the vasa recta allows for the exchange of solutes and water between blood and inters­titial fluid of renal medulla.
 

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