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Iman sarhan
Prof of nephrology
Ain Shams university
ILO’s
• To know the gross external anatomy of the kidney.
• To recognize the site of kidney in abdomen.
• To understand the arterial supply and venous drainage and
innervations.
• To understand the histological structure of the kidney.
• To understand the functional unite (nephron).
• To list different factor affecting glomerular filtration.
• To know the molecular structure of glomerular BM.
• To recognize different types of kidney tubule.
• To understand the function of different parts of nephron.
• To understand the endocrinal function of kidney.
2
Gross External Anatomy of
the Kidney
• The kidneys are paired organs, 11–14
cm in length in adults, 5–6 cm in
width and 3–4 cm in depth.
• The kidneys lie retroperitoneally on
either side of the vertebral column at
the level of T12 to L3.
• The renal parenchyma comprises an
outer cortex and an inner medulla.
Gross External Anatomy of the Kidney
 Near the center of the
concave medial border of the
kidney is a vertical fissure
called the hilum, through
which the ureter leaves and
blood vessels, lymphatic
vessels and nerves enter and
exit.
External Anatomy of Kidney
Three layers of tissue
surround each kidney:
1. The innermost renal
capsule
2. The adipose capsule
3. Outer renal fascia.
 Both kidneys rise and
descend several
centimeters with
respiration
 Innervations : renal
capsule and ureters are
innervated via T10–12
and L1 nerve roots.
Internal Anatomy of
Kidney
• Gross Anatomy of
the Kidney
Internal Anatomy of the Kidney
The nephron is the functional unit of the kidney.Each kidney contain 1 million nephron.
9
Renal vasculature
The Nephron
• Kidney has over 1 million nephrons
composed of a corpuscle and tubule
• Renal corpuscle = site of plasma filtration
– glomerulus is composed of capillaries
where filtration occurs
– glomerular (Bowman’s) capsule is double
walled epithelial cup that collects
filtrate
• Renal tubule
– proximal convoluted tubule
– loop of Henle dips down into medulla
– distal convoluted tubule
• Collecting ducts and papillary ducts drain
urine to the renal pelvis and ureter.
Juxstaglomerular apparatus
Consists of
1. Macula densa
cells lining early DCT between aff. & eff. arterioles
- stimulated by Nacl
- Important in auto-regulation
2. Juxtaglomerular cells
- Modified muscle cells in the media of aff.
arterioles
- Stimulated by blood pressure
- Secret renin
3. Lacis cells
- Between aff & eff arterioles
- Contain renin
Basic Processes of Urine Formation
• Nephrons and collecting ducts perform 3 basic
processes
1. Glomerular filtration
a portion of the blood plasma is filtered into the kidney
Filtration is a function of size of the molecules
2. Tubular reabsorption
• water & useful substances are reabsorbed into the
blood
3. Tubular secretion
• Secretion is important because not all wastes are moved into the
filtrate at filtration.
• Secretion is often the main mechanism by which some compounds
like drugs are removed from the blood.
Glomerular filtration of plasma
 Tubular reabsorption
Tubular secretion
Glomerular filteration rate GFR
volume of glomerular filtrate formed by both kidneys per minute
125ml/min - 7.5 L/h - 180L/ day
Excretion of any substance= filtration –reabsorption + secretion
Net Filtration Pressure
Net filtration pressure (10)=Glomerular hydrostatic pressure (55)-capillary hydrostatc
pressure (15) -blood osmotic pressure (30)
Determination of the Glomerular
Filtration Rate
• Clearance is the amount of substance that cleared from
circulation per min.
• GFR is measured by determining the plasma
concentration and excretion of a substance 
• 1. Neither absorbed nor secreted by the renal tubules.
2. Freely filterable across the glomerular membranes.
3. Not metabolized or produced by the kidneys.
Inulin, 5Kda is the classic marker substance infused to
measure GFR.
GFR= Ui XV /Pi
•
17
• iothalamate and iohexol, and these compounds
can be administered to patients to measure GFR.
• Creatinine clearance.
– The clearance of creatinine is slightly greater than
GFR (15% to 20%) because some creatinine is
secreted.
• Cystatin.
• Typical normal values for GFR in adults are 100
mL/min for women and 120 mL/min for men.
18
Normal Glomerular Capillary
• Urine formation begins at the glomerular filtration barrier.
• The glomerular filter through which the ultrafiltrate has to pass consists of three
layers: the fenestrated endothelium, the intervening glomerular basement
membrane, and the podocyte slit diaphragm.
• The normal thickness of the
basement membrane
equals about 250–300 nm.
• The spaces between foot
processes, with diameters
of 20–60 nm, are called
filtration pores, by which
filtered fluid reaches the
urinary space
21
Normal Glomerular Capillary
Permeable to
Water
Small solute
Myoglobin (16.9 kDa)
Inuline 5 Kda
Albumin 70 KDa
Impermeable to
Reabsorption Routes
Active and Passive Transport Processes
• Paracellular reabsorption
– 50% of reabsorbed material
moves between cells by
diffusion in some parts of
tubule
• Transcellular reabsorption
– material moves through
both the apical and basal
membranes of the tubule
cell by active transport
• There are four major types of carrier-mediated
transporters:
– Facilitated diffusion: carrier proteins expend no
energy moving a molecule along its concentration
gradient.
– Active transport: energy is expended by a carrier
protein to move a molecule against its concentration
gradient.
– Cotransport: multiple molecules are moved along at
least one of the molecule's concentration gradient.
– Countertransport: at least two molecules are moved
in opposite directions following one of their
concentration gradients.
23
Reabsorption in the PCT
• Glucose, amino acids,
lactic acid,
water-soluble vitamins
and other nutrients are
completely reabsorbed
in the first half of the
proximal convoluted
tubule
PCT
26
These solutes are present at the same concentration in proximal tubular fluid as in plasma.
Approximately 60% of the filtered Na+, Cl−, K+, Ca2+, and H2O and more than 90% of the
filtered HCO3
− are absorbed along the proximal tubule.
27
Water Handling by the Human Kidney
• Filtered Water…………………180 L/day
• Reabsorbed Water……………178.5 L/day
• Excreted Water…………………..1.5 L/day
• Fractional Reabsorption.…..…..99.2%
28
29
30
Glucose handling by the kidney
31
The tubular transport maximum for glucose (TmG).When glucose delivery exceeds the
TmG, the excess glucose is excreted in the urine
There is a concentration of a molecule in the tubular fluid at which point the carriers
for that molecule cannot reabsorb all of the molecule because they are saturated.
This concentration is considered the Tm or the renal threshold, above which
the molecule will be found in the urine.
32
Glucose handling by the kidney
34
Na handling
Š iman sarhan
Urinary Na excreation
100-300 meq/l= intake
99 % reabsorped
Filtered Na= plasma
conc X GFR
Na reabsorption
is active process
is derived from
Na-K -ATPase
All natriureteric drug
act on tubules to
inhibit Na
reabsoption and
increase the Na FE
20 to 25 %
60%
3-5%
Fraction excretion of
sodium (FENa )
37
FENa is usually less than 1%.
FENa can also exceed 1% in disease states in which the tubular transport
of Na+ is impaired.
38
Renal Handling of Potassium
39
ADH, antidiuretic hormone;ALDO, aldosterone; CCT, cortical collecting tubule; DCT, distal convoluted tubule;
ICT, initial collecting tubule; MCD, medullary collecting duct; PCT, proximal tubule; R, reabsorption;S, secretion;
TAL, thick ascending limb.
Physiology of Renal Acidification
Proximal
acidification :
PCT
absorption of
HCO3 ( 85%)
Distal Urinary acidification.
 Reabsorption of HCO3
(15%)
 Excretion of fixed
acids through buffering
& Ammonia recycling
and excretion .
The urine PH can be lowered to a max. 4.5-5 in presence of acid load.
This maintained the plasma H+ and PH within a narrow limits
The generated acid =50-100 meq/day
The kidney filters approximately 4320 meq/day of HCO3- (24 meq/L ×180L/day).
Secrete 4320 meq/day of hydrogen ions +the daily acid load.
Renal autoregulation
Regulation of renal blood flow (RBF) and glomerular
filtration rate (GFR)
41
Autoregulation
Hormonal Neural
Sympathetic
stimulation=>VC of
blood vessls of
kidney
Noradrenaline and
angiotensin II=> renal
VC=>dec. RBF.
Prostaglandins and
Kallikrein-kinine
system=>renalVD.
Baroreceptor in
afferent and efferent
arteriol will detect
the changes in
pressure
Autoregulation of GFR
 The most important autoregulation response occurs upon
decrease of systemic blood pressure:
 The afferent arterioles dilate (to increase blood flow to the
glomerulus), the supporting cells of the glomerulus capillaries
relax (causing dilation and increased blood flow), and the
efferent arterioles constrict (causing increased blood pressure
by way of increased post-nephron resistance).
 Upon increased blood pressure at the renal afferent
arterioles, the walls are stretched and smooth muscles
are triggered to contract, thus decreasing the diameter
and decreasing the blood flow to the glomerulus.
42
RAS and BP control
43
Renin Angiotensin Aldosterone
44
Hormonal control of renal function
ADH
45
Regulation of Body Fluid Osmolarity
water intake is
low or fluid is lost
• Urine volume =1
L/day (<0.5
mL/min),
• Uosm) may reach
1200 mOsm/kg
H2O
water intake is
high
• Urine volume=14
L/day (10 mL/min),
• osmolality (75 to
100 mOsm/kg)
46
The hormone responsible for the regulatory changes in urine
volume and tonicity is ADH (vasopressin).
Effect of PTH on the kidney
47
Renal Function
 Filtration occurs exclusively in the renal corpuscle, across
the filtration membrane.
 Water and solute reabsorption occurs primarily along the
proximal convoluted tubules, but also elsewhere along
the renal tubule and within the collecting system.
 Active secretion occurs primarily at the proximal and
distal convoluted tubules.
 Regulation of the final volume and solute concentration
of the urine results from the interaction between the
collecting system and the nephron loops–especially the
long loops of the juxtamedullary nephrons.
48
Hormonal functions
 Erythropoietin is produced by interstitial peritubular cells
in response to hypoxia.
 In vitamin D metabolism, the kidneys hydroxylate 25-
hydroxycholecalciferol to the active form, 1,25-
dihydroxycholecalciferol.
 Renin is secreted from the juxtaglomerular apparatus in
response to reduced afferent arteriolar pressure,
stimulation of sympathetic nerves, and changes in sodium
content of fluid in the distal convoluted tubule at the
macula densa.
49
Summary
 Kidney is bean shape located retro-peritoneal between T12-L3, measure
12x6x3cm.
 Concave medial border of the kidney is a vertical fissure called the hilum,
through which the ureter leaves and blood vessels, lymphatic vessels and
nerves enter and exit.
 Unit function of kidney is nephron (2million nephron receive 25% of
cardiac output).
 Main function :filtration through glomerulus, followed by tubular
reabsorption and secretion, which lead to water and electrolyte regulation,
excretion of waste product, toxins.
 Filtration controlled by filtration pressure, and pores of glomerular cap
membrane.
 Endocrinal function: excretion of erothropoetin, activation of vit D,
secretion of renin.
50

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Physiology of kidney zamala.pdf

  • 1. Iman sarhan Prof of nephrology Ain Shams university
  • 2. ILO’s • To know the gross external anatomy of the kidney. • To recognize the site of kidney in abdomen. • To understand the arterial supply and venous drainage and innervations. • To understand the histological structure of the kidney. • To understand the functional unite (nephron). • To list different factor affecting glomerular filtration. • To know the molecular structure of glomerular BM. • To recognize different types of kidney tubule. • To understand the function of different parts of nephron. • To understand the endocrinal function of kidney. 2
  • 3. Gross External Anatomy of the Kidney • The kidneys are paired organs, 11–14 cm in length in adults, 5–6 cm in width and 3–4 cm in depth. • The kidneys lie retroperitoneally on either side of the vertebral column at the level of T12 to L3. • The renal parenchyma comprises an outer cortex and an inner medulla.
  • 4. Gross External Anatomy of the Kidney  Near the center of the concave medial border of the kidney is a vertical fissure called the hilum, through which the ureter leaves and blood vessels, lymphatic vessels and nerves enter and exit.
  • 5. External Anatomy of Kidney Three layers of tissue surround each kidney: 1. The innermost renal capsule 2. The adipose capsule 3. Outer renal fascia.  Both kidneys rise and descend several centimeters with respiration  Innervations : renal capsule and ureters are innervated via T10–12 and L1 nerve roots.
  • 6. Internal Anatomy of Kidney • Gross Anatomy of the Kidney
  • 7. Internal Anatomy of the Kidney The nephron is the functional unit of the kidney.Each kidney contain 1 million nephron.
  • 9. The Nephron • Kidney has over 1 million nephrons composed of a corpuscle and tubule • Renal corpuscle = site of plasma filtration – glomerulus is composed of capillaries where filtration occurs – glomerular (Bowman’s) capsule is double walled epithelial cup that collects filtrate • Renal tubule – proximal convoluted tubule – loop of Henle dips down into medulla – distal convoluted tubule • Collecting ducts and papillary ducts drain urine to the renal pelvis and ureter.
  • 10. Juxstaglomerular apparatus Consists of 1. Macula densa cells lining early DCT between aff. & eff. arterioles - stimulated by Nacl - Important in auto-regulation 2. Juxtaglomerular cells - Modified muscle cells in the media of aff. arterioles - Stimulated by blood pressure - Secret renin 3. Lacis cells - Between aff & eff arterioles - Contain renin
  • 11. Basic Processes of Urine Formation • Nephrons and collecting ducts perform 3 basic processes 1. Glomerular filtration a portion of the blood plasma is filtered into the kidney Filtration is a function of size of the molecules 2. Tubular reabsorption • water & useful substances are reabsorbed into the blood 3. Tubular secretion • Secretion is important because not all wastes are moved into the filtrate at filtration. • Secretion is often the main mechanism by which some compounds like drugs are removed from the blood.
  • 12. Glomerular filtration of plasma  Tubular reabsorption Tubular secretion Glomerular filteration rate GFR volume of glomerular filtrate formed by both kidneys per minute 125ml/min - 7.5 L/h - 180L/ day Excretion of any substance= filtration –reabsorption + secretion
  • 13. Net Filtration Pressure Net filtration pressure (10)=Glomerular hydrostatic pressure (55)-capillary hydrostatc pressure (15) -blood osmotic pressure (30)
  • 14. Determination of the Glomerular Filtration Rate • Clearance is the amount of substance that cleared from circulation per min. • GFR is measured by determining the plasma concentration and excretion of a substance  • 1. Neither absorbed nor secreted by the renal tubules. 2. Freely filterable across the glomerular membranes. 3. Not metabolized or produced by the kidneys. Inulin, 5Kda is the classic marker substance infused to measure GFR. GFR= Ui XV /Pi • 17
  • 15. • iothalamate and iohexol, and these compounds can be administered to patients to measure GFR. • Creatinine clearance. – The clearance of creatinine is slightly greater than GFR (15% to 20%) because some creatinine is secreted. • Cystatin. • Typical normal values for GFR in adults are 100 mL/min for women and 120 mL/min for men. 18
  • 16.
  • 17. Normal Glomerular Capillary • Urine formation begins at the glomerular filtration barrier. • The glomerular filter through which the ultrafiltrate has to pass consists of three layers: the fenestrated endothelium, the intervening glomerular basement membrane, and the podocyte slit diaphragm. • The normal thickness of the basement membrane equals about 250–300 nm. • The spaces between foot processes, with diameters of 20–60 nm, are called filtration pores, by which filtered fluid reaches the urinary space
  • 18. 21 Normal Glomerular Capillary Permeable to Water Small solute Myoglobin (16.9 kDa) Inuline 5 Kda Albumin 70 KDa Impermeable to
  • 19. Reabsorption Routes Active and Passive Transport Processes • Paracellular reabsorption – 50% of reabsorbed material moves between cells by diffusion in some parts of tubule • Transcellular reabsorption – material moves through both the apical and basal membranes of the tubule cell by active transport
  • 20. • There are four major types of carrier-mediated transporters: – Facilitated diffusion: carrier proteins expend no energy moving a molecule along its concentration gradient. – Active transport: energy is expended by a carrier protein to move a molecule against its concentration gradient. – Cotransport: multiple molecules are moved along at least one of the molecule's concentration gradient. – Countertransport: at least two molecules are moved in opposite directions following one of their concentration gradients. 23
  • 21. Reabsorption in the PCT • Glucose, amino acids, lactic acid, water-soluble vitamins and other nutrients are completely reabsorbed in the first half of the proximal convoluted tubule
  • 22. PCT 26 These solutes are present at the same concentration in proximal tubular fluid as in plasma. Approximately 60% of the filtered Na+, Cl−, K+, Ca2+, and H2O and more than 90% of the filtered HCO3 − are absorbed along the proximal tubule.
  • 23. 27
  • 24. Water Handling by the Human Kidney • Filtered Water…………………180 L/day • Reabsorbed Water……………178.5 L/day • Excreted Water…………………..1.5 L/day • Fractional Reabsorption.…..…..99.2% 28
  • 25. 29
  • 26. 30
  • 27. Glucose handling by the kidney 31 The tubular transport maximum for glucose (TmG).When glucose delivery exceeds the TmG, the excess glucose is excreted in the urine There is a concentration of a molecule in the tubular fluid at which point the carriers for that molecule cannot reabsorb all of the molecule because they are saturated. This concentration is considered the Tm or the renal threshold, above which the molecule will be found in the urine.
  • 29. 34
  • 30. Na handling Š iman sarhan Urinary Na excreation 100-300 meq/l= intake 99 % reabsorped Filtered Na= plasma conc X GFR Na reabsorption is active process is derived from Na-K -ATPase All natriureteric drug act on tubules to inhibit Na reabsoption and increase the Na FE 20 to 25 % 60% 3-5%
  • 31. Fraction excretion of sodium (FENa ) 37 FENa is usually less than 1%. FENa can also exceed 1% in disease states in which the tubular transport of Na+ is impaired.
  • 32. 38
  • 33. Renal Handling of Potassium 39 ADH, antidiuretic hormone;ALDO, aldosterone; CCT, cortical collecting tubule; DCT, distal convoluted tubule; ICT, initial collecting tubule; MCD, medullary collecting duct; PCT, proximal tubule; R, reabsorption;S, secretion; TAL, thick ascending limb.
  • 34. Physiology of Renal Acidification Proximal acidification : PCT absorption of HCO3 ( 85%) Distal Urinary acidification.  Reabsorption of HCO3 (15%)  Excretion of fixed acids through buffering & Ammonia recycling and excretion . The urine PH can be lowered to a max. 4.5-5 in presence of acid load. This maintained the plasma H+ and PH within a narrow limits The generated acid =50-100 meq/day The kidney filters approximately 4320 meq/day of HCO3- (24 meq/L ×180L/day). Secrete 4320 meq/day of hydrogen ions +the daily acid load.
  • 35. Renal autoregulation Regulation of renal blood flow (RBF) and glomerular filtration rate (GFR) 41 Autoregulation Hormonal Neural Sympathetic stimulation=>VC of blood vessls of kidney Noradrenaline and angiotensin II=> renal VC=>dec. RBF. Prostaglandins and Kallikrein-kinine system=>renalVD. Baroreceptor in afferent and efferent arteriol will detect the changes in pressure
  • 36. Autoregulation of GFR  The most important autoregulation response occurs upon decrease of systemic blood pressure:  The afferent arterioles dilate (to increase blood flow to the glomerulus), the supporting cells of the glomerulus capillaries relax (causing dilation and increased blood flow), and the efferent arterioles constrict (causing increased blood pressure by way of increased post-nephron resistance).  Upon increased blood pressure at the renal afferent arterioles, the walls are stretched and smooth muscles are triggered to contract, thus decreasing the diameter and decreasing the blood flow to the glomerulus. 42
  • 37. RAS and BP control 43
  • 39. Hormonal control of renal function ADH 45
  • 40. Regulation of Body Fluid Osmolarity water intake is low or fluid is lost • Urine volume =1 L/day (<0.5 mL/min), • Uosm) may reach 1200 mOsm/kg H2O water intake is high • Urine volume=14 L/day (10 mL/min), • osmolality (75 to 100 mOsm/kg) 46 The hormone responsible for the regulatory changes in urine volume and tonicity is ADH (vasopressin).
  • 41. Effect of PTH on the kidney 47
  • 42. Renal Function  Filtration occurs exclusively in the renal corpuscle, across the filtration membrane.  Water and solute reabsorption occurs primarily along the proximal convoluted tubules, but also elsewhere along the renal tubule and within the collecting system.  Active secretion occurs primarily at the proximal and distal convoluted tubules.  Regulation of the final volume and solute concentration of the urine results from the interaction between the collecting system and the nephron loops–especially the long loops of the juxtamedullary nephrons. 48
  • 43. Hormonal functions  Erythropoietin is produced by interstitial peritubular cells in response to hypoxia.  In vitamin D metabolism, the kidneys hydroxylate 25- hydroxycholecalciferol to the active form, 1,25- dihydroxycholecalciferol.  Renin is secreted from the juxtaglomerular apparatus in response to reduced afferent arteriolar pressure, stimulation of sympathetic nerves, and changes in sodium content of fluid in the distal convoluted tubule at the macula densa. 49
  • 44. Summary  Kidney is bean shape located retro-peritoneal between T12-L3, measure 12x6x3cm.  Concave medial border of the kidney is a vertical fissure called the hilum, through which the ureter leaves and blood vessels, lymphatic vessels and nerves enter and exit.  Unit function of kidney is nephron (2million nephron receive 25% of cardiac output).  Main function :filtration through glomerulus, followed by tubular reabsorption and secretion, which lead to water and electrolyte regulation, excretion of waste product, toxins.  Filtration controlled by filtration pressure, and pores of glomerular cap membrane.  Endocrinal function: excretion of erothropoetin, activation of vit D, secretion of renin. 50