1. 1
Chapter Eight
Renal Physiology

2. Kidneys: Functions, Anatomy, and Basic Processes
Functions of the kidneys
1. Maintaining H2O & electrolyte balance in the body
2. Maintaining the proper osmolarity of body fluids, primarily
through regulating H2O balance
3. Maintaining proper plasma volume
- important in the long-term regulation of BP
-accomplished through the kidneys’ regulatory role in salt
and H2O balance
4. Helping maintain the proper acid–base balance of the body
- by adjusting urinary output of H+ and HCO3
-
2

3. 5. Excreting (eliminating) the end products (wastes) of bodily
metabolism
-urea (from proteins), uric acid (from nucleic acids), creatinine
(from muscle creatine), bilirubin (from hemoglobin), and
hormone metabolites
6. Excreting many foreign compounds
-drugs, food additives, pesticides, and other exogenous
nonnutritive materials
7. Producing erythropoietin
- a hormone that stimulates RBC production
- Kidney secretes erythropoietin in response to hypoxia
- Erythropoietin stimulates erythropoiesis
- Renal failure  renal anemia
3

4. 9. Producing renin
- part of the RAAS
- important in the regulation of plasma volume and therefore
BP.
10. Converting vitamin D into its active form
(1,25-dihydroxyvitamin D3)
- involved with calcium balance
11. Gluconeogenesis
-synthesis of new glucose from noncarbohydrate sources
(AAs from protein and glycerol from triglycerides).
- occurs in the liver (most), but a substantial fraction occurs in
the kidneys(during a prolonged fast).
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5. 5
Functional Anatomy of Kidneys
 2 Kidneys
-Lie outside the peritoneal
cavity in the posterior
abdominal wall.
- one on either side of the
vertebral column
- each weighing about 150g in
adult
-extend from the 12th T to 3rd L
- 11cm long,6cm wide& 3cm
thick
-Blood supply: Renal arteries
and veins
Ureter, Urinary bladder,Urethra

6. 6
Layers of kidney

7. 7
Nephron
• The structural & functional unit of the kidney
• Each kidney contains about 1 million nephrons
• Each nephron is capable of forming urine
• The nephron has two components:
• Vascular
• Tubular

8. 8

9. Juxtaglomerular Apparatus (JGA)
• Combination of vascular & tubular component next to the
glomerulus form a structure called juxtaglomerular
apparatus.
• Is the site of renin (enzyme that results in angiotensin
formation) production
• Comprises the macula densa, extraglomerular mesangial cells,
and juxtaglomerular (JG) cells
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10. 10

11. Types of nephrons
• Two types: cortical nephron &juxtamedullary nephron
Cortical nephron
• Glomerulus is located in the outer region of the cortex
• Loop of Henle is short and does not penetrate deeply into the
medulla
• Tubular portion is supplied by network of peritubular
capillaries
• In humans, 70 to 80% of the nephrons are cortical.
Juxtamedullary nephron
• Glomerulus is located in the inner region of the cortex, close
to the medulla
• Loop of Henle is significantly longer, penetrating to the
innermost region of the medulla
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12. • The peritubular capillaries forms vasa recta(“straight
vessels”)
- vasa recta descend deep into the medulla, form a hairpin
loop, and then ascend back toward the cortex (similar to LH)
- they run in close association with the long loops of Henle.
• Tubular portion is supplied by straight capillaries called vasa
recta
• 20-30% of nephrons in the human kidney are juxtamedullary.
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13. 13

14. 14
Fluid flow through the nephron

15. 15
Renal Blood Flow (BF)
• BF through both kidneys is about 1100 ml/min.
– about 22 % of the cardiac output
• BF is highest in the cortex than other layers
- permits high rate of glomerular filtration
• Lower medullary BF helps to maintain medullary hyperosmolarity
• Blood supplied to the kidney by renal artery
– Arises directly from abdominal aorta

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17. 17
Urine Formation
• A result of three basic renal processes
1. Glomerular filtration
2. Tubular reabsorption
3. Tubular secretion
• The filtered fluid is modified by reabsorption and secretion as it
passes along the tubule

18. Filtration
 The movement of fluid and solutes from the glomerular
capillaries into Bowman’s capsule.
 A nonselective process (everything in the plasma except for
the plasma proteins is filtered)
 ~20% of the plasma is filtered
 On average, this results in a glomerular filtration rate(GFR)
of 125 ml/min or180 L of filtrate per day.
Reabsorption
 The movement of filtered substances from the renal tubule
into the peritubular capillaries
 Takes place throughout the tubule
 ~178.5 L of filtrate are reabsorbed, resulting in an average
urine output of 1.5 L per day.
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19. Secretion
 the movement of selected unfiltered substances from the
peritubular capillaries into the renal tubule
 Any substance that is filtered or secreted, but not reabsorbed,
is excreted in the urine.
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20. 20

21. 21
- Poorly reabsorbed (E.g. Creatinine, urea, uric acid, urate)
• Therefore excreted in large amount
- Highly reabsorbed E.g. Electrolytes
- Completely reabsorbed E.g. Amino acids and glucose
• Never appear in the urine
- Poorly reabsorbed + secreted
E.g. Foreign substances and drugs

22. 22
• Around 180 L/day of fluid filtered and around 178.5 L
reabsorbed. Each of the 3 basic processes are regulated according
to the needs of the body.
A. Freely filtered but neither reabsorbed nor secreted
Excretion rate = filtration rate
E.g. ~ Creatinine
B. Freely filtered but partially
reabsorbed,
Excretion rate=filtration-reabsorption
E.g. Electrolytes
C. Freely filtered ,completely reabsorbed
but not secreted
E.g. Glucose

23. D. Feely filtered & also secreted but not reabsorbed
Excretion rate=filtration rate + secretion rate
E.g. Organic acids & basis
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24. 24
Glomerular Filtration
• The first step in urine formation
• Begins with filtration of large amounts of fluid through the
glomerular capillaries into Bowman's capsule
– Most substances in the plasma are freely filtered
– Exceptions: proteins, cellular elements e.g. RBC, WBC
 this is facilitated by filtration barrier (glomerular
membrane)
• The filtration barrier is composed of three structures:
• Glomerular capillary wall
• Basement membrane
• Inner wall of Bowman’s capsule

25. Glomerular capillary wall
• Consists of a single layer of endothelial cells (like the walls of
other capillaries).
• However, these cells are specialized in that they are fenestrated
(makes them 100 times more permeable than the typical
capillary).
• These pores are too small, however, to permit the passage of
blood cells through them.
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26. Basement membrane
• An acellular meshwork consisting of collagen & glycoproteins.
• Collagen provides structural strength
• Glycoproteins (-vely charged) prevent the filtration of plasma
proteins into Bowman’s capsule
Inner wall of Bowman’s capsule
• Consists of specialized epithelial cells referred to as podocytes.
• The podocytes have foot-like processes that project outward.
• The processes of one podocyte interdigitate with the processes
of an adjacent podocyte, forming narrow filtration slits.
• These slits provide an ample route for the filtration of fluid.
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27. 27

28. 28
Glomerular Filtration Rate (GFR)
• The total amount of filtrate formed per minute by the kidneys
• In the average adult human, the GFR is about 125 ml/min, or
180 L/day
• Factors governing filtration rate at the capillary bed are:
– Filtration coefficient(Kf)
– Net filtration pressure
GFR = Kf x net filtration pressure

29. Filtration coefficient
• is determined by the surface area and permeability of the
filtration barrier.
• An increase in the filtration coefficient leads to an increase in
GFR; if the filtration coefficient decreases, then GFR decreases.
Net filtration pressure
• The pressure responsible for filtrate formation
• is determined by the following forces.
• Glomerular capillary blood pressure
• Plasma colloid osmotic pressure
• Bowman’s capsule hydrostatic pressure
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30. Glomerular capillary blood pressure
• the fluid (hydrostatic) pressure exerted by the blood within the
glomerular capillaries.
• It pushes blood out of the capillary
• depends on contraction of the heart and the resistance to
blood flow offered by the afferent and efferent arterioles.
• An estimated average value =55 mm Hg
• Higher than capillary blood pressure elsewhere (b/c diameter
of the afferent arteriole > efferent arteriole & high resistance
offered by the efferent arterioles).
• It is the major force producing glomerular filtration.
• Favors filtration
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31. 31

32. Plasma-colloid osmotic pressure
• Caused by the unequal distribution of plasma proteins across
the glomerular membrane.
• Plasma proteins cannot be filtered, they are in the glomerular
capillaries but not in Bowman’s capsule
• The concentration of H2O is higher in Bowman’s capsule
• H2O tend to move by osmosis from Bowman’s capsule into the
glomerulus, opposes glomerular filtration.
• ~ 30 mm Hg
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33. Bowman’s capsule hydrostatic pressure
• The pressure exerted by the fluid in this initial part of the
tubule.
• It pushes the fluid out of Bowman’s capsule
• It is estimated to be about 15 mm Hg
• It also tends to oppose filtration
Net filtration pressure = PGC – (πGC + PBC)
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35. 35
Filtration fraction
• The fraction of the renal plasma flow that is filtered.
• GFR = 125ml/min & renal plasma flow = 605ml/min
Filtration fraction averages about 0.2
•Thus, 20% of plasma passing through kidneys is filtered.

36. 36
Tubular Reabsorption
• The transfer of substances from the tubular lumen into the
peritubular capillaries.
• Selective (unlike glomerular filtration) and quantitatively large.
• Two steps involved in reabsorption
1. Across the tubular epithelial membranes into the renal
interstitial fluid.
• Paracellular: the substance goes through the matrix of
the tight junctions that link each epithelial cell to its
neighbor.
• Transcellular: a substance goes through the cells, across
the luminal membrane facing the tubular lumen and
across the basolateral membrane facing the interstitium.

37. 37

38. 2. Across the peritubular capillary membrane into the blood
Across the capillary endothelium Peritubular capillary blood
Summary:
Filtrate within tubular lumen
Across the luminal membrane of the epithelial cell
Through the cytoplasm of the epithelial cell
Across the basolateral membrane of the epithelial cell
Through interstitial fluid
Across the capillary endothelium
Peritubular capillary blood
• This pathway is referred to as transepithelial transport.
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39. 39
Tubular reabsorption can be active or passive
1. Passive reabsorption
• If all steps in the transepithelial transport of a substance from the
tubular lumen to the plasma are passive.
• Occurs down electrochemical or osmotic gradients
2. Active reabsorption
• If any one of the steps in the transepithelial transport of a
substance requires energy = active reabsorption.
• Occurs against an electrochemical gradient.
• Can be primary or secondary active transport

40. 40

41. Primary Active Transport
 Energy from hydrolysis of ATP
e.g. Na+/ K+ ATPase, H+ ATPase, H+/ K+ ATPase, Ca++
ATPase
 Na+ reabsorption in the proximal tubule
-Extensive Na+-K+ ATPase on basolateral sides of the
epithelium
- Upon hydrolysis of 1ATP  3 Na+ out & 2 K+ in
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42. 42
Passive diffusion of Na+ across the luminal membrane of the cell
and active transport on the basolateral membrane

43. 43
Secondary Active Reabsorption
• Two or more substances interact with a specific membrane
protein.
- transported together across the membrane
• Does not require energy directly from ATP
• Can be symport (co-transport) or antiport (counter transport)

44. 44
• One of the substances(usually Na+) diffuses down its electro-
chemical gradient,
 energy is released
- Drive another substance against its electrochemical gradient
E.g. Transport of glucose & amino acid via Na symport
- After entry into the cell, glucose & amino acids exit across the
basolateral membranes by facilitated diffusion

45. 45

46. 46
Tubular Maximum
• Is a maximum limit to the rate at which the solute can be
transported across the tubule
- due to saturation of the transport systems
• When the filtered load (quantity of any substance filtered per
minute) exceeds the capacity of the carrier proteins & enzymes
involved in the transport process, substance will appear in the
urine.
 A good example the glucose transport system in the
proximal tubule

47. • The quantity of any substance filtered per minute, known as its
filtered load.
Filtered load of a sub. = GFR x plasma[sub.]
Filtered load of glu. = GFR x plasma [glu.]
= 125 ml/min x 100 mg /100 ml
=125 mg/min
• At a constant GFR, the filtered load of glucose is directly
proportional to the plasma glucose concentration.
Tubular maximum for glucose
• The Tm for glucose averages 375 mg/min; that is, the glucose
carrier mechanism is capable of actively reabsorbing up to 375
mg of glucose per minute.
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48. Renal threshold for glucose
• It is the plasma concentration at which the Tm is reached
(300mg/100ml) and glucose first starts appearing in the urine.
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49. Tubular secretion
• The transfer of substances from the peritubular capillaries into
the renal tubule for excretion in urine.
• Important for the regulation of potassium and hydrogen ions
in the body.
• It is also responsible for removal of many organic compounds
from the body [metabolic wastes, foreign compounds(e.g.
drugs)].
• Most substances are secreted by secondary active transport.
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50. 50
Reabsorption & Secretion along Different Parts of the Nephron
1. Proximal Tubule
• Highly metabolic & have large numbers of mitochondria.
• Rich in proteins for secondary active transport
• Has extensive brush border on the luminal side of the membrane
– surface area for absorption
• Reabsorb about 65% of the filtered Na+, Cl-, HCO3
-,H2O & K+
and essentially all the filtered glucose & amino acids.
• Also secrete organic acids, bases, and hydrogen ions
NB: Water enters the tubular epithelial cells through water
channels, also referred to as aquaporins.
- they are always open in the early regions of the tubule.

51. 51
The secretion of hydrogen ions into the tubular lumen is an important
step in the removal of bicarbonate ions from the tubule

52. • Sodium ions leave the filtrate and enter the tubular epithelial cell
by way of the following processes.
– Na+/glucose, Na+/amino acid, Na+/phosphate, and Na+/lactate
symporter mechanisms; Na+/H+ antiporter mechanism: first
half of the proximal tubule
– Coupled with Cl– reabsorption by way of transcellular and
paracellular pathways: second half of the proximal tubule
• In the second half of the proximal tubule, little glucose and amino
acids remain to be reabsorbed.
• The total solute conc. remains essentially the same all along the
proximal tubule because of the extremely high permeability of this
part of the nephron to water.
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53. 53
2. Solute and Water Transport in the Loop of Henle
A. The descending part of the thin segment
• Highly permeable to water
– About 20% of the filtered water is reabsorbed
• Moderately permeable to most solutes, including urea & Na+
B. The ascending limb
• Virtually impermeable to water (important for concentrating the
urine.)
Thick segment:
• Has thick epithelial cells that have high metabolic activity and
are capable of active reabsorption of Na+, Cl-, and K+.

54. 54
- About 25 % of the filtered loads of Na+, Cl-, & K+ are
absorbed.
• Considerable amounts of other ions, such as Ca++, HCO3
-, and
Mg++, are also reabsorbed.
• In the thick ascending loop, 1-Na+, 2-Cl-, 1-K+ co-transporter
exists- transports these three ions from the tubular lumen into
the cell
• This segment also secretes hydrogen ions into the tubular
lumen.
• As the tubular fluid flows to the distal tubule, it becomes very
dilute.

55. 55

56. 56
3. Early Distal Tubule
• The first part of the DT forms part of the JG complex
- provides feedback control of GFR and blood flow
• Reabsorbs most of the ions, including Na+,Ca2+,Mg2+ & Cl-
• 5 % of the filtered load of Na+ & Cl- are reabsorbed
• Impermeable to water & urea
• Thus, reabsorption of NaCl occurs without water, which further
dilutes the tubular fluid.
• also called diluting segment.

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58. 58
4. Late Distal Tubule and Cortical Collecting Tubule
• Have two cell types
(1) Principal cells:
• Reabsorb Na+ ,Cl- and H2O.
• Secrete K+.
• Aldosterone increases Na+ reabsorption and increases K+
secretion.
• The action of aldosterone takes several hours to develop
because new protein synthesis of Na+ channels is required.

59. • Antidiuretic hormone (ADH) increases H2O permeability.
- Insert of H2O channels in the luminal membrane
• In the absence of ADH, the principal cells are virtually
impermeable to water.
(2) Intercalated cells:
• Secrete H+ by an H+-ATPase, which is stimulated by aldosterone.
• Reabsorb HCO3
- & K+ by an H+,K+-ATPase.
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61. 61
5. Medullary Collecting Duct
• Reabsorb > 10 % of the filtered water and Na+
• The final site for processing the urine
– determine the final urine output of water & solutes.
• Few mitochondria in epithelial cells
• Permeability to water is controlled by the level of ADH
(vasopressin)
• Permeable to urea (raise the osmolality in medullary
interstitium of the kidneys)
• Secrete H+ (H+ ATPase) against a large concentration gradient
- Plays a key role in regulating acid-base balance

62. 62
Concentration of Urine
• Osmolar of glomerular filtrate = osmolar of plasma
=300mOsm/L
• Osmolar of cortical interstitium = osmolar of plasma
• But, proceeding towards the inner part of medulla osmolar is
very high = (1200mOsm/L)

• This gradual increase in osmolarity of medullary interstitium is
called medullary gradient
• Normally urine is 4x concentrated than glomerular filtrate
– osmolar of urine ~1200mOsm/L

63. 63
Transport of Urine from Kidney into Bladder
• Urine from the bladder has the same composition as fluid
flowing out of the CD.
• Urine from the CD into the renal calyces, stretches the calyces
– initiates peristaltic (forward-pushing) contractions that spread
to the renal pelvis
– then downward along the length of the ureter forcing urine
from the renal pelvis toward the bladder.

64. • The walls of the ureters contain smooth muscle innervated by:
– sympathetic nerves
• inhibit peristaltic contractions in the ureter
– parasympathetic nerves
• enhanced peristaltic contractions in the ureter
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65. 65
• The ureters penetrate the wall of the bladder obliquely.
• The normal tone of the detrusor muscle (make up the wall of the
urinary bladder) compresses the ureter.
– prevent backflow of urine from the bladder when pressure
builds up in the bladder
Physiologic Anatomy of the Bladder
– The urinary bladder is a smooth muscle chamber
– composed of two main parts:
1. The body
• the major part of the bladder in which urine collects
2. The neck
• a funnel-shaped extension of the body
• The lower part is posterior urethra or internal sphincter

66. 66
Anatomy of the Bladder
Ureter
Prostate
gland
Detrusor
smooth muscle
External
urethral sphincter
Pelvic floor
Body
Neck

67. 67
Innervation of the Bladder
1. Pelvic nerves
– The principal nerve supply of the bladder
– Originate from S-2 & S-3 segment of spinal cord
– Have two types of nerve fibers:
A. Sensory nerve fibers
– detect the degree of stretch in the bladder wall
• mainly responsible for initiating the reflexes that cause
bladder emptying
B. Motor nerve fibers
– are parasympathetic fibers and innervate the detrusor muscle
& posterior urethra

68. 68
Functions of Parasympathetic
 contraction of detrusor muscles & relaxation of internal sphincter
 it is called nerve of micturition or nerve of emptying
2. The Skeletal Motor Fibers or Pudendal Nerves
– These are somatic nerve fibers
– arise from S2 & S3 segment of spinal cord
– innervate & control the voluntary skeletal muscle of the
external urethral sphincter
– the sphincter contracts always (prevent urine from escaping
through the urethra)
– during micturion this nerve is inhibited  relaxation of the
sphincter urination

69. 69
3. Sympathetic Innervations
• Arise mainly from L-2 & some from L-1 segment of the
spinal cord
• Supply detrusor muscles & internal urethral sphincter
– Cause relaxation of detrusors & constriction of the sphincter
• Results in bladder filling

• Hence nerve of filling
– not essential in micturition (inhibit urination by relaxing
detrusor muscle and contracting the internal urethral
sphincter)

70. 70
Innervations of bladder & sphincters

71. 71
Micturation
• the process of bladder emptying
• This involves two main steps:
1. Progressive bladder filling
– until the tension in its walls rises above a threshold level
– this elicits the second step, micturition reflex
2. The micturition reflex - empties the bladder
– due to stimulation of stretch receptors on the wall of bladder
& urethra

72. • when  200ml of urine collected  pressure within the bladder
  stretching of the walls   stimulation of stretch
receptors sensory information to sacral segment of spinal cord
 parasymp. to bladder & urethra   micturition contraction
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74. 74

75. 75
Facilitation or Inhibition of Micturition by higher Brain
center
• The micturition reflex is a completely autonomic spinal cord
reflex but can be inhibited or facilitated by centers in the brain
• These centers include:
1. Strong facilitative & inhibitory centers in the brain stem
– located mainly in the pons
– Inhibitory centers inhibit the sacral center
– Facilitatory centers facilitate the sacral center
2. Several centers located in the cerebral cortex
– mainly inhibitory but can become excitatory

76. 76
The higher centers exert final control of micturition as
follows:
A. keep the reflex partially inhibited
– except when micturition is desired
B. can prevent micturition, even if the reflex occurs by continual
tonic contraction of the external sphincter until a convenient
time presents
C. When it is time to urinate, the cortical centers facilitate the
sacral micturition centers to help initiate a micturition reflex and
inhibit the external sphincter so that urination can occur

77. READING ASSIGNMENT
1. List and describe types of abnormal micturition reflexes
2. Discuss the following disorders of renal functions
• Nephrotic syndyrome
• Nephritic syndrome
• Chronic glomerulonephritis
• Polycystic kidney diseases
• Acute renal failure
• Chronic renal failure
• Nephrolithiasis
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