1. 25
P A R T A
The Urinary System

2. Kidney Functions
Filtration – over 200 liters of blood filtered daily, allowing toxins, metabolic wastes, and excess ions to leave the body in urine
Regulates fluid & electrolyte balance
Assists with blood acid – base balance
Gluconeogenesis during prolonged fasting
Production of renin to help regulate blood pressure and erythropoietin to stimulate RBC production
Activation of vitamin D
Produces some thrombopoietin

3. Urinary System Organs
Kidneys (2)
Paired ureters – transport urine from the kidneys to the bladder
Urinary bladder – provides a temporary storage reservoir for urine
Urethra – transports urine from the bladder out of the body

4. Urinary System Organs
Figure 25.1a

5. Kidney Location and External Anatomy
Approximate size 12 x 6 x 3 in centimeters
Approximate weight 150 grams
The kidneys lie in a retroperitoneal position in the superior lumbar region – generally T12 – L3 – thus some protection from ribs 11 and 12
The right kidney is lower than the left because it is crowded by the liver
The lateral surface is convex; the medial surface is concave
The renal hilus leads to the renal sinus
Ureters, renal blood vessels, lymphatics, and nerves enter and exit at the hilus

6. Layers of Tissue Supporting the Kidney
Renal capsule – fibrous capsule that prevents kidney infection
Adipose capsule – fatty mass that cushions the kidney and helps attach it to the body wall
Renal fascia – outer layer of dense fibrous connective tissue that anchors the kidney
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7. Kidney Location and External Anatomy
Figure 25.2a

8. Internal Anatomy (Frontal Section)
Cortex – the light colored, granular superficial region
Medulla – exhibits 6 – 12 cone-shaped medullary (renal) pyramids separated by columns
Each renal pyramid has a tip called the renal papillae which is perforated by 20 or so openings of the ducts of Bellini
The medullary pyramid and its surrounding corical capsule constitute a lobe (each kidney generally has between 6 to 12 lobes)
Collecting System – begins with minor calyx
Each renal papillae is covered by a cup like structure known as the ostium (mouth) of the Minor Calyx ( thus for every lobe of the kidney there is a minor calyx.

9. Several minor calyces join together to form a major calyx.
Internal Anatomy
Several minor calyces join together to form a major calyx.
The major calyces join together to form the renal pelvis
Urine flows through the renal pelvis into a ureter
From the ureter urine enters the urinary bladder
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11. Blood and Nerve Supply
Approximately one-fourth (1200 ml) of systemic cardiac output flows through the kidneys each minute
Arterial flow into and venous flow out of the kidneys follow similar paths
The nerve supply is via the renal plexus. The renal plexus consists of unmyelinated sympathetic fibers that travel with the arterial supply. The cell bodies are located in the aortic and celiac plexuses.
Lymphatic supply to kidney poorly understood

12. Renal Vascular Pathway Aorta renal artery Anterior and Posterior division of renal artery 5 segmental arteries (do not anastomose) Lobar arteries Interlobar arteries Arcuate arteries Interlobular arteries Afferent arterioles Glomerulus Efferent arterioles Peritubular Cap and Vasa Recta (arteriolae rectae and vena rectae) Arcuate veins (if from the vena rectae) – deliver into stellate veins then to interlobular veins if from cortical peritubular capillaries then to arcuate veins Interlobar veins renal veins
Figure 25.3c

13. Internal Anatomy
Figure 25.3b

14. Capillary Beds
Figure 25.5a

15. Renal Arteriogram

16. Capillary Beds of the Nephron
Every nephron has two capillary beds
Glomerulus
Peritubular capillaries OR Vasa Recta
Each glomerulus is:
Fed by an afferent arteriole
Drained by an efferent arteriole

17. Capillary Beds
Peritubular beds are low-pressure, porous capillaries adapted for absorption that:
Arise from efferent arterioles
Cling to adjacent renal tubules
Empty into the renal venous system
Vasa recta – long, straight efferent arterioles of juxtamedullary nephrons

18. Capillary Beds
Figure 25.5a

19. Functional Unit of the Kidney – Uriniferous tubules Functional Unit – least amount of anatomy to explain the entire physiology The uriniferous tubules consists of the nephron (generally referred to as the functional unit of the kidney) and a portion of the collecting duct
The nephron consists of a) the glomerulus b) Bowman’s capsule c) the proximal convoluted tubule d) the Loop of Henle e) the Distal convoluted tubule and f) the connecting tubule
The combination of the glomerulus and Bowman’s capsule constitutes the “Renal Corpuscle”
Renal corpuscle – the glomerulus and its Bowman’s capsule
Glomerular endothelium – fenestrated epithelium that allows solute-rich, virtually protein-free filtrate to pass from the blood into the glomerular capsule

21. The Nephron
Figure 25.4a, b

22. The nephrons are all located in the cortical region of the kidneys – but they are at three levels in the cortex . The outer cortical nephrons, the mid-cortical nephrons and the inner cortical nephrons termed the “Juxtamedullary nephrons – approximately 15% of nephrons. The juxtamedullary nephrons have the longest loops of Henle (associated with concentrating the urine). Each kidney has approximately 1 – 1.3 million nephrons.
The renal corpuscle which consists of the glomerulus and Bowman’s capsule is where the actual filtration of the blood occurs.

23. Nephron Positions Outer cortical Mid-cortical (not shown)
Juxta-medullary
Notice the length of the loops
of Henle – longest in the
Juxta-medullary nephrons –
More concentrating of urine
ability

24. Cortical nephrons – 85% of nephrons; located in the cortex
Juxtamedullary nephrons:
Are located at the cortex-medulla junction
Have loops of Henle that deeply invade the medulla
Have extensive thin segments
Are involved in the production of concentrated urine

25. Renal Corpuscle
The glomerulus is a tuft of fenestrated capillaries that allows a filtrate of the blood to enter Bowman’s capsule
Between the capillary loops of the glomerulus are Mesangial cells (intraglomerular) and some located at the vascular pole of the renal corpuscle (extraglomerular).
The intraglomerular Mesangial cells are a) phagocytic thus cleaning the filter b) contractile in that they have receptors for vasoconstrictors like angiotensin II c) help support the capillaries in regions where the visceral layer of Bowman’s capsule does not come in contact with the capillaries.
The extraglomerular mesangial cells are connected by gap junctions and may serve as a communication between macula densa and granular cells.

27. Three jobs to make urine
1. Filtration – removal of substances from the blood at the filter (renal corpuscle)
2. Reabsorption – returning much of the filtrate (minus most of the waste) back into the blood – reason – too much has been filtered
3. Secretion – active transport of substances absolutely needed to filtered into the kidneys in areas after the filter

28. Mechanisms of Urine Formation
Urine formation and adjustment of blood composition involves three major processes
Glomerular filtration
Tubular reabsorption
Secretion
Figure 25.8

29. Filtration - Composition of the Filter
The capillary fenestra – range between 70 – 90 nm – this prevents the formed elements of the blood (except a few WBCs that can perform diapedesis) from being filtered along with any macromolecules (some of the plasma proteins) whose effective size exceeds the diameter of the fenestra (atomic mass exceeds 70,000 AMUs)
The Basal Lamina (300nm thick) consists of three layers the lamina densa (has type IV collagen) in the middle surrounded by a lamina rara on each side (lamina rara has the negatively charged substance heparin sulfate). The Lamina Densa traps larger proteins > 69,000 AMU and the negatively charged Lamina rara impedes negatively charged molecules from leaving (most of the plasma proteins are negatively charged).

30. Filter Continued Anatomy of the Glomerular (Bowman’s) Capsule
Bowman’s capsule is composed of two layers – the internal visceral layer that actually abuts the glomerular capillaries. This layer consists of modified, branching epithelial podocytes.
Extensions of the octopus-like podocytes terminate in foot processes – primary processes and secondary processes (pedicels)
Filtration slits – 20 – 40 nm width openings between the foot processes that allow filtrate to pass into the capsular space

32. Filtration Slits are covered
The filtration slits are covered by a 6nm thick slit diaphragm which extends between the secondary pedicels
The slit diaphragm has circular pores that are approximately 3-5 nm in diameter
As a result of the filtration anatomy – substances smaller than 3 nm easily transverse the anatomical filter – those larger than 5 nm generally do not cross . Examples of these substances would be water, electrolytes, glucose, amino acids, small proteins, urea, uric acid, creatinine and others

33. Figure 25.7a

34. Figure 25.7b, c

35. Glomerular Filtration
Principles of fluid dynamics that account for tissue fluid in all capillary beds apply to the glomerulus as well
The glomerulus is more efficient than other capillary beds because:
Its filtration membrane is more permeable
Glomerular blood pressure is higher
It has a higher net filtration pressure
Plasma proteins are not filtered and are used to maintain oncotic pressure of the blood

36. Figure 25.8

37. Net Filtration Pressure (NFP)
The pressure responsible for filtrate formation
NFP equals the glomerular hydrostatic pressure (HPg) minus the oncotic pressure of glomerular blood (OPg) combined with the capsular hydrostatic pressure (HPc)
10 mmHg = 55 mm Hg – (30 mmHg + 15mmHg)
Usual pressures in most capillaries are:
10 mmHg = (35mmHg + 1mmHg) – (26 mmHg)
NFP = HPg – (OPg + HPc)

38. Figure 19.16

39. Figure 25.9

40. NFP = pressure out of capillary – pressure into
Comparison of NFP
NFP = pressure out of capillary – pressure into
Forces out = MAP at capillary + Interstitial Fluid Osmotic Pressure
Forces into = Interstitial Hydrostatic Pressure + Blood Osmotic Pressure
MAP at general Capillary – mmHg but at glomerulus 55 mmHg - why? efferent arteriole narrower than afferent arteriole – won’t blow out capillary due to being wrapped by podocytes
Interstitial Fluid Osmotic Pressure 1 mm Hg in most capillaries – 0 mmHg in kidney due to non-filtration of the plasma proteins

41. Blood osmotic pressure 26 mmHg in most capillaries but 30 mmHg in Glomerulus due to increased concentration of plasma proteins due to non-filtration
Interstitial fluid hydrostatic pressure 0 mmHg in most tissues but 15 mmHg in kidney due relative lack of lymphatics and the narrowness of the Proximal Convoluted Tubule compared to Bowman’s space.

42. Vascular Resistance in Microcirculation
Afferent and efferent arterioles offer high resistance to blood flow
Blood pressure declines from 95mm Hg in renal arteries to 8 mm Hg in renal veins (in most other venules and veins it drops to 10 – 15 mm Hg)
The reason is due to the two arteriole anatomy- one arteriole coming into the glomerulus (afferent arteriole) and one coming out (efferent arteriole) – the combination of these two resistors significantly drops the pressure

43. Vascular Resistance in Microcirculation
Resistance in afferent arterioles:
Protects glomeruli from fluctuations in systemic blood pressure – if blood pressure gets to high – vasoconstrict so as to not blowout the glomerular capillaries – if to low vasodilate to let more blood into glomerulus so Glomerular Filtration Rate does not drop.
Resistance in efferent arterioles:
Reinforces high glomerular pressure – vasoconstriction gives a better back pressure
Reduces hydrostatic pressure in peritubular capillaries – this provides a better suction pressure in the peritubular capillaries for reabsorption of water

44. Clearances to be Discussed Later
Renal Blood Flow (RBF) – how much whole blood flows to both kidneys in a minute – generally about 25% of cardiac output – average 1250 ml per minute
Renal Plasma Flow (RPF)– since the glomerulus filters out the formed elements – then really what goes into Bowman’s capsule is filtered plasma RPF = RBF(1 − HCT) (Determined by Clearance of PAH)
Glomerular Filtration Rate (GFR) – what is the amount of the plasma that is filtered in one minute – on average approximately 125 ml per minute (Determined by Clearance of Creatinine)
Clearances to be Discussed Later
Filtration Fraction – what percentage of plasma is filtered in a minute FF = GFR / RPF x 100

45. Regulation of Glomerular Filtration
Three mechanisms control the GFR
Renal autoregulation (intrinsic system) inside kidney
Neural controls (Extrinsic)
Hormonal mechanism (the renin-angiotensin system)- Extrinsic
THESE WILL BETTER BE DISCUSSED LATER

46. The start of Reabsorption in the Renal Tubule
The ultra-filtrate of the blood now enters the first tubule (small tube) which is the Proximal convoluted tubule (PCT) – its walls are lined with cuboidal epithelial cells with numerous microvilli (increase surface area for reabsorption) and mitochondria (lots of active transport – both primary and secondary)
The speed at which the glomerulus filters blood is termed the Glomerular Filtration Rate which on average is 125 ml per minute so in a day you put on average over liters of filtrated blood into the kidneys
You only have 3 – 6 liters of blood so you can see that you must reabsorb most of your fluid back into the blood stream
Thus the main job of the PCT is Reabsorption of much of your ultrafiltrate of the blood

47. Reabsorption in the PCT
Generally 100% of glucose, amino acids, lactate, vitamins, and other non-waste organic substances
80% of filtered bicarbonate
65% of sodium, water
60% of chloride
55% of potassium
Almost all of the uric acid and 50% of the urea reabsorbed but later secreted

48. Tubular Reabsorption Two routes – transcellular or paracellular
Transcellular – through the cell
Paracellular – between the cells
Most travel by transcellular - transported substances move through three membranes
1. Luminal and 2. basolateral membranes of tubule cells and 3. endothelium of peritubular capillaries
Ca2+, Mg2+, K+, and some Na+ are reabsorbed via paracellular pathways Chloride also is reabsorbed paracellular in the proximal part of PCT and transcellular in Distal part
The epithelial cells are linked by leaky tight junctions

49. Renal Tubule
Figure 25.4b

50. Sodium Reabsorption: Primary Active Transport
Sodium reabsorption is almost always by active transport
Na+ enters the tubule cells at the luminal membrane
Is actively transported out of the tubules by a Na+-K+ ATPase pump

51. Figure 25.12

52. Sodium Reabsorption: Primary Active Transport
From there it moves to peritubular capillaries due to:
Low hydrostatic pressure (as a result of narrower efferent arteriole giving resistance)
High osmotic pressure of the blood (as a result of increased concentration of plasma proteins – remember they were never filtered in glomerulus but water was taken out – thus increase in effective concentration of these proteins
Na+ reabsorption provides the energy and the means for reabsorbing most other solutes

53. Reabsorption by PCT Cells
Active pumping of Na+ drives reabsorption of:
Water by osmosis, aided by water-filled pores called aquaporins (obligatory water reabsorption)
Aquaporins I are permanent residents of the PCT epithelial cells unlike in the DCT where they will be controlled by antidiuretic hormone
Cations and fat-soluble substances by diffusion- as the water leaves the concentration of cations and fat soluble substances increase thus forcing diffusion of them – an example of solute following solvent
Organic nutrients and selected cations by secondary active transport

54. Small proteins that mistakenly get filtered are removed by pinocytosis
Secondary Transporters cause reabsorption of the most of the organic substances like glucose, amino acids, lactic acid, sulfate and phosphate
The Secondary Transport substances are limited by a Transport Maximum (Tm) – the amount removed cannot exceed the amount of transport carriers – another term for this is to exceed renal threshold
H+ removal will be discussed later in my renal acid- base discussion

55. Figure 25.12

56. Non-reabsorbed Substances
A transport maximum (Tm):
Reflects the number of carriers in the renal tubules available
Exists for nearly every substance that is actively reabsorbed
When the carriers are saturated, excess of that substance is excreted – exceeds Tm or also termed exceeds renal threshold

57. Nonreabsorbed Substances
Substances are not reabsorbed if they:
Lack carriers (secondary transport)
Are not lipid soluble
Are too large(and water soluble) to pass through membrane pores (thus electrolytes pass through membrane pores)
Creatinine is an important non-reabsorbed substance (but its non- reabsorption is advantageous in medicine in that it can be used to determine the Glomerular Filtration Rate
GFR rate determination – discussed later

58. Figure 25.11

59. Figure 25.12

60. After the PCT comes the Loop of Henle
Loop of Henle – a hairpin-shaped loop of the renal tubule
Functions to further perform reabsorption
Helps with acid – base balance due to its Na+/H+ antiporters in the thick ascending limb
A major function is the control of osmotic pressure as a result of its ability to concentrate the urine
The longer the loops (in juxtamedullary nephrons) the more the ability to concentrate the urine ( To be discussed later)

61. Parts of Loop of Henle
Proximal part is similar to the proximal convoluted tubule – and some refer to it as part of the PCT (pars recta of PCT) others refer to it as the descending thick limb of the Loop of Henle
Then comes the descending thin limb which is lined by simple squamous cells. Its length varies depending on the location of nephrons in the cortex. Juxtamedullary nephrons have the longest thin limbs.
Next is the bend (actual Loop) – then the ascending thin limb
Then the ascending thick limb which is lined by short simple cuboidal cells – this area sometimes is termed the pars recta of the Distal Convoluted Tubule – in that it is similar in construct to the DCT

62. Renal Tubule
Figure 25.4b

63. Reabsorption in the Loop of Henle
The loop of Henle sets the stage for independent regulation of both the volume and osmolarity of body fluids (reabsorption of substances can be selective in accordance with the body’s need for that substance and the body’s need to maintain the proper blood osmolarity ( mOsm).
Na+-K+- 2Cl- symporters located in the ascending thick limb reclaim Na+, Cl-, and K+ ions from the tubular lumen fluid.
Because K+ leakage channels return much of the K+ back into tubular fluid, the main effect of the Na+-K+-Cl- symporters is reabsorption of Na+ and Cl-.

64. Loop of Henle
Descending thin limb of Loop of Henle totally permeable to water (aquaporins I) but mostly impermeable to solutes – thus water exits from tubule but few solutes – thus the intraluminal osmotic pressure gets high
Ascending limb – not at all permeable to water (no aquaporins) but very permeable to solutes (passive transport) additionally some active transport via–
The 2 Cl-, Na+, K+ symporter

65. Ascending Limb of Loop of Henle
On basolateral side of the epithelial cells of the thick ascending limb has the sodium potassium pump creating a intracellular sodium concentration gradient
On the luminal side of the epithelial cells there is a symporter (secondary active transport) that uses sodium as the driver (energy provider) and carries 2 chlorides and one potassium in addition to the one sodium
Also a Na+/H+ antiporter (This is used for acid/base balance discussed later)
Some 50% of sodium exits via the paracellular route

66. Symporters in the Loop of Henle
Thick limb of loop of Henle has Na+ K- Cl- symporters that reabsorb these ions
K+ leaks through K+ channels back into the tubular fluid leaving the interstitial fluid and blood with a negative charge
Cations passively move to the vasa recta

67. Loop of Henle Reabsorption
35% of Chloride reabsorbed – leaving approximately 5% to be absorbed, if necessary, later (60% reabsorbed in the PCT)
20 – 30% of Na+ reabsorbed (leaving approximately 5 – 15% to be reabsorbed later- 65% in PCT) –depending on blood sodium levels and blood osmotic pressure- controlled by aldosterone
20 – 30% of K+ reabsorbed (leaving 15 – 25% to be absorbed later – 55% in PCT) depending on blood K+ levels in association with Na+ levels – again aldosterone

68. Loop of Henle Reabsorption Continued
20 – 30% of Ca++ reabsorbed the amount left is reabsorbed later in the DCT in accordance with the blood calcium levels which are controlled by the hormones PTH & Calcitonin
10 – 20% of HCO3- reabsorbed (leaving 0 – 10%) controlled by acid-base balance
15% of H2O reabsorbed – leaving as much as 20% (65% removed in the PCT) – the amount left in tubules to be absorbed later as a result of the homeostatic control of Blood Osmotic Pressure. This is controlled by the hormones ADH and Aldosterone

69. Distal Convoluted Tubule (DCT)
The DCT can be divided into a proximal portion and a very distal portion. The very distal portion leading into the Connecting Tubules has receptors for ADH and Aldosterone. The proximal portion does not.
We will now examine the proximal portion

70. Renal Tubule
Figure 25.4b

71. Proximal Portion of the DCT
The Proximal portion of the DCT has three regions
A) The Pars Recta which really is the continuation of the ascending thick limb of the Loop of Henle
B) Pars Convoluta – which the official DCT
C) Interposed at the junction between the Pars Recta and Pars Convoluta is a specialized region known as the Macula Densa (Dense spot of specialized cells)

72. DCT
The cells lining the DCT are short cuboidal cells with no microvilli
The DCT is not permeable to water or urea
The DCT has Na+-Cl- symporters in the apical membrane – thus more Na+ and Cl- are reabsorbed from the filtrate in the tubule
In the basolateral membranes Na+/K+ pumps acts as the driving force to operate the symporters
Also in basolateral surface are Cl- leak channels thus allowing Cl- to leak into the peritubular capillaries
The cells have Parathyroid Hormone receptors thus its stimulation causes passive reabsorption of Ca++

73. Reabsorption in the DCT
As fluid flows along the DCT, reabsorption of Na+ and Cl- continues due to Na+-Cl- symporters.
Na+ and Cl- then reabsorbed into peritubular capillaries
The DCT serves as the major site where parathyroid hormone stimulates reabsorption of Ca+2.
DCT is not very permeable to water so the solutes are reabsorbed with little accompanying water.

74. Filtrate Amounts Entering the DCT
20% of the original filtrate of water enters the DCT
15% - 25% of Potassium enters DCT
5% - 15% of Sodium enters DCT
5% of Chloride enters DCT
0 – 10% of Bicarbonate enters DCT
10% - 20% of Calcium
Overall the proximal part of the DCT automatically removes approximately 2% - 3% of the NaCl

75. Connecting Tubules
The distal convoluted tubules of several nephrons join to form a short connecting tubule that leads into the collecting duct (tubule)
The distal portion of the distal convoluted tubule and the connecting tubules (as well as the collecting duct) have two types of specialized epithelial cells termed the Principal cells and the Intercalated cells.

76. Two important cell types are found here
Connecting Tubules
Two important cell types are found here
Intercalated cells (Type A & B)
Cuboidal cells with microvilli
Function in maintaining the acid-base balance of the body
Principal cells
Cuboidal cells without microvilli
Help maintain the body’s water and salt balance

77. Principal Cells
The Principal cells have receptors for ADH and Aldosterone
The DCT, Connecting Tubules and Collecting Duct are normally impermeable to water – they have no Aquaporins I. However, when stimulated by ADH they can carry in tiny membrane bound vesicles containing Aquaporins II. The vesicles fuse with the cell membrane inserting the Aquaporins II into the cell membrane of the Principal cells – thus opening channels to the reabsorption of water.

78. Principal Cells
Aldosterone stimulates the Principal Cells to insert more Na+/K+ exchangers in the cell’s apical surface and produce more Na+/K+ pumps on the basolateral surfaces – thus this causes the secretion into the luminal fluid of K+ and the reabsorption of Na+
As a result of these actions - Aldosterone lowers blood potassium levels and raises blood sodium levels

79. Actions of the Principal Cells
Na+ enters principal cells through leakage channels
Na+ pumps keep the concentration of Na+ in the cytosol low
Cells secrete variable amounts of K+, to adjust for dietary changes in K+ intake
down concentration gradient due to Na+/K+ pump
Aldosterone increases Na+ and water reabsorption & K+ secretion by principal cells by stimulating the synthesis of new pumps and channels.

80. Collecting Duct (CD)
The Collecting Duct is termed this because it collects modified filtrate from several nephrons
It has the same properties of the distal portion of the DCT and connecting tubules – principal cells and intercalated cells
It is where true concentration of the urine can occur as a result of the counter-current multiplier system (to be discussed later)
It is the last area in the kidney where the filtrate can be modified – thus once it leaves the CD it is officially urine

81. The Collecting Duct travels down through the cortex of the kidney then through the medullary portion of the kidney
In the inner areas of the medullary portion of the kidneys – several collecting ducts come together to form Papillary Collecting Tubules (Ducts of Bellini). These Papillary Ducts open at the renal papillae – thus the urine then enters the minor calyx.

82. Nephron Anatomy
Figure 25.5a

83. Substances reabsorbed in PCT include:
Summary of Absorptive Capabilities of Renal Tubules and Collecting Ducts
Substances reabsorbed in PCT include:
Sodium, all nutrients, cations, anions, and water
Urea and lipid-soluble solutes
Small proteins
Loop of Henle reabsorbs:
H2O, Na+, Cl, K+ in the descending limb
Ca2+, Mg2+, and Na+ in the ascending limb

84. Collecting duct absorbs:
Summary of Absorptive Capabilities of Renal Tubules and Collecting Ducts
DCT absorbs:
Ca2+, Na+, H+, K+, and water
HCO3 and Cl
Collecting duct absorbs:
Water and urea

85. Juxtaglomerular Apparatus (JGA)
The JGA is so named because it is piece of specialized renal anatomy juxta (next to) positioned to the glomerulus
It is composed of two structures the Juxtaglomerular cells of the afferent arteriole (sometimes efferent) in contact with the macula densa cells of the DCT

86. Juxtaglomerular Cells
Arteriole walls have juxtaglomerular (JG) cells
Enlarged, smooth muscle cells
Have secretory granules containing renin
Act as mechanoreceptors

87. Macula Densa Macula densa
Tall, closely packed distal tubule cells
Lie adjacent to JG cells
Function as chemoreceptors or osmoreceptors
Mesangial cells: (previously mentioned but mentioned again on next slide)
Have phagocytic and contractile properties
Influence capillary filtration

88. Mesangial Cells
Between the capillary loops of the glomerulus are Mesangial cells (intraglomerular) and some located at the vascular pole of the renal corpuscle (extraglomerular).
The intraglomerular Mesangial cells are a) phagocytic thus cleaning the filter b) contractile in that they have receptors for vasoconstrictors like angiotensin II c) help support the capillaries in regions where the visceral layer of Bowman’s capsule does not come in contact with the capillaries.
The extraglomerular mesangial cells are connected by gap junctions and may serve as a communication between macula densa and granular cells.

89. Juxtaglomerular Apparatus (JGA)
Figure 25.6

90. Regulation of Glomerular Filtration
The kidney attempts to maintain a normal GFR despite the body’s MAP
If the GFR is too high:
Needed substances cannot be reabsorbed quickly enough and are lost in the urine
If the GFR is too low:
Everything is reabsorbed, including wastes that are normally disposed of

91. Regulation of the Glomerular Filtration Rate (GFR)
Three mechanisms control the GFR
Renal autoregulation (intrinsic system)
Neural controls
Hormonal mechanism (the renin-angiotensin system)

92. Autoregulation entails two types of control
Intrinsic Controls
Under normal conditions, renal autoregulation maintains a nearly constant glomerular filtration rate – this system can work effectively as long as MAP is between 80 mmHg and 180 mmHg. During very low MAP like in hemorrhage it cannot work properly and must be overtaken by Extrinsic Controls.
Autoregulation entails two types of control
Myogenic – responds to changes in pressure in the renal blood vessels – tonus of the smooth muscle
Flow-dependent tubuloglomerular feedback – senses changes in the juxtaglomerular apparatus

93. Myogenic Tone
If too much pressure placed on the walls of the afferent arteriole (to fast of a blood flow) – vasoconstriction will occur
If too little pressure (too slow of a blood flow) – vasodilation will occur

94. Tubuloglomerular Feedback
The Macula Densa in the wall of the DCT senses osmotic pressure and chemicals
If the osmotic pressure is high and or the NaCl level is high – this suggests there is too fast of a flow into the tubules (it appears to the MD cells that there is not enough time for adequate reabsorption of solutes- thus too many solutes are still in modified filtrate)
In this case the Macula Densa sends a vasoconstrictor substance (not sure what it is but think it is ATP) to the afferent arteriole to cause vasoconstriction of the AA – thus reducing blood flow
If too little osmotic pressure or NaCl then the opposite occurs

95. Autoregulatory mechanisms maintain a fairly constant GFR – if the MAP stays between 80 mm Hg and 180 mm Hg.
When the MAP is too high or too low – must add in “Extrinsic Controls”

96. When the sympathetic nervous system is at rest:
Extrinsic Controls
When the sympathetic nervous system is at rest:
Renal blood vessels are maximally dilated
Autoregulation mechanisms prevail

97. Extrinsic Controls
Under stress it is important to protect the MAP of the body, in particular the brain, this may be at the detriment of the kidneys:
Norepinephrine is released by the sympathetic nervous system
Epinephrine is released by the adrenal medulla
Both the afferent arterioles and efferent arterioles have Alpha1 receptors – the afferent arterioles have more Apha1 receptors than the efferent arterioles.

98. With little sympathetic stimulation such as at rest both the AA and EA are both maximally dilated. With moderate sympathetic stimulation the AA and EA are both marginally constricted to the same amount. With maximal sympathetic stimulation as during heavy exercise or hemorrhage, vasoconstriction of the Afferent arterioles predominates. This vasoconstriction causes a significant decrease in GFR – thus increasing the intravascular volume in the rest of the body.
The sympathetic nervous system also stimulates the renin-angiotensin mechanism

99. Renin-Angiotensin Mechanism
Is triggered when the JG cells release renin
Renin acts on angiotensinogen to release angiotensin I
Angiotensin I is converted to angiotensin II
Angiotensin II:
Causes mean arterial pressure to rise
Stimulates the adrenal cortex to release aldosterone
As a result, both systemic and glomerular hydrostatic pressure rise

100. Actions of Angiotensin II (All cause an increase in MAP)
1. Powerful vasoconstrictor
2. Stimulates reabsorption of sodium both directly by acting on renal tubules and indirectly by stimulating the release of Aldosterone
3. Stimulates release of ADH from posterior pituitary and stimulates thirst center
4. Increases fluid reabsorption – thus increasing intravascular volume. AII decreases peritubular hydrostatic pressure because of vasoconstriction of efferent arterioles – thus more water goes into peritubular capillaries. Efferent arterioles have AII receptors.
5. Works on mesangial cells causing them to contract – thus reducing cross sectional area of the glomerular capillaries. The decreases GFR.

101. Renin release is triggered by:
Reduced stretch of the granular JG cells
Stimulation of the JG cells by activated macula densa cells – possibly due to decreased ATP secretion and/or increased release of PGE2
Direct stimulation by epinephrine and norepinephrine on the JG cells’ 1-adrenergic receptors (1 also on the heart)

102. Renin Release
Figure 25.10

103. Other Factors Affecting Glomerular Filtration
Prostaglandins (PGE2 and PGI2)
Vasodilators produced so as to counteract the actions of sympathetic stimulation and angiotensin II – the kidney needs to protect itself (keep some modicum of GFR even in the face of failing systemic BP.
Are thought to prevent renal damage when peripheral resistance is increased
Nitric oxide – vasodilator produced by the vascular endothelium
Intrarenal Angiotensin II – kidney produces some AII to oppose actions of PGE2
Vasoconstrictors
Adenosine – vasoconstrictor of renal vasculature
Endothelin – a powerful vasoconstrictor secreted by tubule cells

104. Atrial Natriuretic Peptide Activity
ANP reduces blood Na+ which:
Decreases blood volume
Lowers blood pressure
ANP lowers blood Na+ by:
Acting directly on medullary ducts to inhibit Na+ reabsorption
Counteracting the effects of angiotensin II
Indirectly stimulating an increase in GFR reducing water reabsorption

105. Secretion
Filtration – was taking materials out of the blood and putting into the kidneys at Bowman’s capsule
Reabsorption – was placing certain substances back into the blood – a recapturing process
Secretion is removing certain unwanted substances from the blood that were not able to be filtered at the renal corpuscle (glomerulus & Bowman’s capsule)

106. Secretion
Why? Not all the blood can be filtered into Bowman’s capsule on one pass through the kidneys (Filtration Fraction) – if it did we would lose all our blood volume temporarily into the kidneys. It would remain there until it could be reabsorbed back into the bloodstream in the proximal convoluted tubule – the efferent arteriole would have no blood and dry out.
Thus blood borne waste and other substances desiring filtration must continue in the blood. These substances must travel throughout the entire circulation until they return to the kidneys for filtration on the second pass.
The body does not want some of these substances to wait for a second pass – a role for secretion.

107. Tubular Secretion - Purposes
1. Disposes of substances such as certain drugs and metabolites, that are tightly bound to plasma proteins. Because the plasma proteins are not generally filtered, these substances must be secreted.
2. Elimination of undesirable substances or end products that have been reabsorbed by passive processes. Urea and uric acid are handled this way. Urea cycling will be discussed later.
3. Ridding the body of excess K+. Since most K+ is reabsorbed – it sometimes must be removed (prevent hyperkalemia) as a result of Aldosterone.
4. Control of pH – secretion of H+ if needed

108. Secretion
Tubular secretion is the transfer of materials from peritubular capillaries to renal tubular lumen. Tubular secretion is caused mainly by active transport but sometimes facilitated diffusion as in urea recycling (to be discussed later).
Usually only a few substances are secreted. These substances are present in great excess, or are natural poisons.
Many drugs are eliminated by tubular secretion.

109. Secretion
Substances such as H+, K+, NH4+, creatinine, and certain organic acids either move into the filtrate from the peritubular capillaries or are synthesized in the tubule cells and secreted.
Example of drugs secreted are penicillin, glucuronide, cimetidine.

110. RC = UV/P GFR Calculation GFR is calculated using renal clearance
RC = renal clearance rate
U = concentration (mg/ml) of the substance in urine
V = flow rate of urine formation (ml/min)
P = concentration of the same substance in plasma

111. Renal Blood Flow (RBF) – how much whole blood flows to both kidneys in a minute – generally about 25% of cardiac output – average 1250 ml per minute
Renal Plasma Flow (RPF)– since the glomerulus filters out the formed elements – then really what goes into Bowman’s capsule is filtered plasma RPF = RBF(1 − HCT)
Glomerular Filtration Rate (GFR) – what is the amount of the plasma that is filtered in one minute – on average approximately 125 ml per minute
Filtration Fraction – what percentage of plasma is filtered in a minute FF = GFR / RPF x 100

112. Type of Substance Needed for GFR Determination
Only filtered not reabsorbed or secreted – thus only involves the filter
Filtered in accordance with its concentration in the blood
Closest substance the body makes is Creatinine
Creatinine is slightly secreted
Inulin is the best substance – but the body does not make it

113. Creatine and Creatinine
In humans and animals, approximately half of stored creatine originates from food (mainly from fresh meat). Since vegetables do not contain creatine, vegetarians show lower levels of muscle creatine which, upon creatine supplementation, rise to a level higher than in meat-eaters.
In humans, about half of the daily creatine is biosynthesized from three different amino acids - arginine, glycine, and methionine in the kidneys, pancreas and liver. The rest is taken in by alimentary sources. Ninety-five percent of creatine is later stored in the skeletal muscles (must be transported there).
Creatinine is a break-down product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body (depending on muscle mass).

115. Creatine kinase (CK), also known as creatine phosphokinase (CPK) or phosphocreatine kinase, is an enzyme expressed by various tissue types. It catalyses the conversion of creatine and consumes adenosine triphosphate (ATP) to create phosphocreatine and adenosine diphosphate (ADP).
In tissues that consume ATP rapidly, especially skeletal muscle, but also brain and smooth muscle, phosphocreatine serves as an energy reservoir for the rapid regeneration of ATP. Thus creatine kinase is an important enzyme in such tissues.