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B Y
T E K L E H .
Renal Physiology
2
3
Functions of the Kidneys
 Kidneys perform a variety of functions for homeostasis.
1. Filter 180 liters of blood daily to eliminate toxins & wastes
2. Excretion of metabolic waste products (urea, uric acid & creatinine)
3. Regulate Blood volume & Blood pressure by control water balance
4. Regulate RBC formation by producing Erythropoietin (EPO)
5. Regulate electrolyte balance (Na+, K+, Ca2+)
6. Regulate acid-base balance (by control H+ and HCO3 level).
7. Regulate body fluid Osmolarity (280 mOsm/l) through water balance
8. Enzyme and Hormone production: Renin, Erythropoietin, ….
9. Drug metabolism and chemical Detoxification
10. Glucose production during starvation (gluconeogenesis)
4
1. Cortex- outer layer which contain
major portion of nephrons
(functional units)
2. Medulla- inner layer which
contains
 Pyramids-triangular shaped
structures,
 Renal papilla: is tip of pyramid
 Renal calyx – minor and major
 Renal pelvis- large area (cavity)
which collects urine from calyx
(minor & major) and drain it in
to Ureters.
5
Internal structure of Kidneys…
Renal Blood Circulation
 The renal arteries deliver about
21% (1200 ml/min) of the
resting cardiac output to the
kidneys (Approx. one-fourth)
 90% blood flow to cortex
 Renal artery branches
extensively within the kidney
into smaller arteries called
afferent arterioles.
 Renal blood flow has mainly
two purposes:
1. Filtration
2. Renal tissue oxygenation 6
Characteristics of Renal Blood Flow
7
 In kidney, Two capillary beds
1. Glomerular capillary: High
hydrostatic pressure (60 mmHg)→
important for Filtration process
2. Peritubular capillaries (vasa
recta): Low hydrostatic pressure
(13 mmHg) → importantant for
Reabsorption process
Peritubular capillaries
Nephrons
 Nephrons: are structural & functional units of kidneys
• There are One million nephron in each kidney
• Only 25% of kidney nephrons is needed to adequately maintain all the essential
renal excretory and regulatory functions.
 Each nephron consists of two parts:
1. Renal Corpuscle - contains glomerular capillaries & Bowman’s capsule
- Function: Site of blood plasma filtration.
2. Renal Tubules-Contains tubular structures that extends beyond corpuscle
-Function: Reabsorption & Secretion purpose
 These tubular structures include; PCT- Proximal Convoluted Tubule, LOH- Loop of Henle,
DCT- Distal Convoluted Tubule, CD- Collecting Duct
8
Nephron…
9
Renal Corpuscle
10
Renal Tubule
 Proximal convoluted tubule (PCT) – PCT reabsorbs water &
solutes from filtrate & secretes substances into it.
 Loop of Henle – is U-shaped loop of the renal tubule
• Proximal part is similar to the proximal convoluted tubule.
• Proximal part is followed by the thin segment & thick segment
• Distal convoluted tubule (DCT) – continuation of the loop of
Henle and function more in secretion than reabsorption. 11
Renal Tubule
 Connecting Tubules: The distal portion of the distal
convoluted tubule nearer to the collecting ducts.
 Two important cell types are found here:
1. Intercalated cells
• Cuboidal cells with microvilli.
• Function in maintaining the acid-base balance of the body.
2. Principal cells
• Cuboidal cells without microvilli.
• Help maintain the body’s water and salt balance
12
Types of Nephrons
13
14
15
Mechanisms of Urine Formation
Urine formation and
adjustment of blood
composition involves
three major processes
1. Glomerular Filtration
2. Tubular Reabsorption
3. Tubular Secretion
Mechanisms of Urine Formation…
16
17
575mlmin
Glomerular Filtration
18
 Glomerular filtration- is the filtration of fluid through the
glomerular capillaries in to bowman's capsule
 The Glomerular Filtrate contains all plasma components
except plasma proteins (albumin, globulin & fibrinogen) and
formed elements (blood cells) -RBC, WBC Platelets.
 The kidneys filter the body’s entire plasma volume 60 times
each day.(3L plasma x 60 times/day= 180L/day).
 Plasma proteins (albumin) are not filtered and are used to
maintain colloid osmotic pressure of the blood.
 Filtration is selective in terms of size but non-selective in
terms of usefulness (contains both useful & non-useful).
19
Q. What derives filtration across the walls of glomerular capillaries?
Capillary blood pressure favors filtration process.
Colloid osmotic pressure & Capsular pressure oppose filtration .
Diameter of A.A > E.A→ blood
damming up in capillary → ↑CBP
Filtration Membrane
20
 Fluid filtered from glomerulus into
Bowman’s capsule pass through the 3 layers
that make up filtration membrane.
1. Endothelial cells with fenestrated
capillaries (pores)
2. Basement Membrane
3. Podocyte Cells with filtration slits in
inner layer of Bowman’s capsule
 This allows huge filtration in the
glomerular capillaries except blood cells
and plasma proteins.
Filtration Membrane…
21
Filtration Membrane…
• Filtration membrane is highly permeable to water and small
molecules (less than 10.000 MW)
• Large molecules (more than 70.000 MW especially proteins
are not filtered due to their large size and negative electrical
charge because their passage is repulsed by negatively
charged glycoproteins present on endothelial pores,
basement membrane and podocytes.
 Factors that determining the glumerular filterability
 Molecular weight
 Charges of the molecule
22
Glomerular Filtration Rate (GFR)
23
Factors that affect Glomerular Filtration Rate (GFR)
↑ Renal blood flow -- ↑ GFR, b/se it ↑capillary pressure
↑ Plasma protein -- ↓ GFR, b/se it ↑ oncotic pressure.
Hemorrhage -- ↓ GFR, b/se it ↓renal blood flow
Sympathetic Ns--↓ GFR, b/se afferent arteriole constriction
Tubular Reabsorption
 Reabsorption-is the process of taking useful substances from
the filtrate in to the blood (not to be lost in the urine)
 The kidneys produces 180 liters of filtrate per day and normal
urinary output in per day 1 to 2 liters.
 Approximately 99% of the filtrate is reabsorbed back into the
blood in the peritubular capillaries & Only 1% forms urine.
 Reabsorbed substances are carried to the venous system →
heart
 Some reabsorption is passive & most is active transport
 Majority of reabsorption takes place in the Proximal tubule.
Reabsorption…
25
Reabsorption Path
26
Na+ Dependent Reabsorption
27
Reabsorption in Proximal Tubule
28
Obligatory water reabsorption in the PCT with Sodium ions
(100%)
Reabsorption in Descending LOH
29
30
Reabsorption in Ascending LOH
(Na-K-2Cl-
Cotransport)
Counter Current Mechanism
31
32
Reabsorption in Distal Tubule
33
Role of Aldosterone in Regulation Na+ & K+
34
Reabsorption in Collecting Duct
Facultative water reabsorption in the CD by the help of ADH.
Role of ADH (Vasopressin)
35
(ADH)
36
 Secretion – is the process of adding unwanted substance from
blood (peritubular) in to the filtrate for excretion with the urine.
 Only 20% of the plasma entering the kidneys is filtered.
 Secretion :allows for rapid elimination of substances from the
plasma via extraction of the 80% of unfiltered plasma in peritubular
capillaries and adding it to the substances already in tubule as result
of filtration
 Tubular secretion is the reverse of reabsorption process.
 Some materials move from the blood (peritubular capillaries) into the
renal tubules are: H+, K+ , Creatinine & some drugs like penicilin.
 Tubular secretion is an active process.
Tubular Secretion
37
Summary of Urine Formation
A.LOH- is
impermeable
to water.
38
Dilute & Concentrated Urine
The kidneys can excrete urine of varying concentrations depending on the
body’s state of hydration (overhydration and dehydration state).
Plasma Clearance
 Plasma clearance: The volume of plasma which is cleared
from a particular substance by the kidney (in urine).
 Plasma clearance expresses the kidneys’ effectiveness in
removing various substances from blood to the environment
 Clearance is non-invasive way to measure GFR
 Inulin clearance and Creatinine clearance: important to
measure kidney function by estimating GFR.
39
Plasma Clearance…
 GFR is an index of kidney function
 Measurement of GFR: can be measured by means of the inulin
clearance and estimated by means of the creatinine clearance
1. Inulin: a polymer of fructose, precisely measure GFR (Standard)
 Freely filtered into the Bowman’s capsule
 Not reabsorbed, secreted or metabolized by the nephron
 Non-endogenous, has to be infused intravenously
2. Creatinine: endogenously released into plasma by skeletal muscle
metabolism, is used to measure GFR (accurate measure GFR)
 Not as accurate as inulin as a small quantity is secreted into the proximal
tubule.
 amount excreted > amount filtered
 Reasonably accurate measurement of GFR (easy to monitor)
40
Plasma Clearance…
41
Excretion
42
Excretion refers removal of a
substance from the body.
All plasma constituents filtered
or secreted but not reabsorbed
remain in the tubules and pass
into the renal pelvis to be
excreted as urine & eliminated
from body.
 Urine output=1.5 liters/day).
Regulation of Acid-Base Balance by Kidney
43
Regulation of Acid-Base Balance (Buffer System)
 Buffer is substance that
stabilizes [H+] when
H+ ions are added or
removed from a solution.
 They do not eliminate
H+ from body –
reversibly bind
H+ until balance is re-
established and form
conjugated base or acid.
44
 Ureters: Retroperitoneal (behind
peritoneum, like kidney)
• Tubular organ 25cm long each
• Extends from the renal pelvis to
the bladder
• The smooth muscle in the wall of
the ureter contracts in peristaltic
waves to propel urine toward the
urinary bladder
• Gravity also assist to propel urine
45
Transportation, Storage & Elimination of Urine…
Urinary bladder
• The urinary bladder is a
muscular sac which is found
behind the pubic bones.
• In women, the bladder is
inferior to the uterus;
• In men, the bladder is superior
to the prostate gland.
• The bladder is a reservoir for
accumulating urine, and it
contracts to eliminate urine.
46
Transportation, Storage & Elimination of Urine…
47
• On the floor of the bladder is a triangular area called
the trigone, and it does not expand during urinary
filling.
• The points of the triangle are the openings of the
two ureters and that of the urethra
• The smooth muscle layer in the wall of the bladder
is called the detrusor muscle.
• Contraction of dertusor muscles causes urination
Transportation, Storage & Elimination of Urine…
 Urethra
• Transports urine from urinary
bladder to outside
• Its wall contains mucus secreting
urethral glands
 Parts of male urethra
1. Prostatic urethra
2. Membranous urethra
3. Penile urethra
• Urethral orifice is on glans penis. 48
Transportation, Storage & Elimination of Urine…
Q. What is prostate hypertrophy &
its effect on urination?
Impede urine flow or ↑urine flow ?
Micturition Reflex
49
Micturition (Urination ) is the process of bladder emptying.
2 mechanisms: the Micturition reflex and Voluntary control
Renal Failure
1. Acute: Sudden onset, rapid reduction in urine output
- usually reversible
2. Chronic: Progressive, not reversible
Up to 75% function can be lost before it is noticeable.
Generalized Site of Disease:
1. Prerenal: Inadequate renal blood flow
2. Intrarenal: Nephron damage
3. Postrenal: Obstruction, Structural defects
50

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Renal Physiology: Functions of the Kidneys and Mechanisms of Urine Formation

  • 1. B Y T E K L E H . Renal Physiology
  • 2. 2
  • 3. 3
  • 4. Functions of the Kidneys  Kidneys perform a variety of functions for homeostasis. 1. Filter 180 liters of blood daily to eliminate toxins & wastes 2. Excretion of metabolic waste products (urea, uric acid & creatinine) 3. Regulate Blood volume & Blood pressure by control water balance 4. Regulate RBC formation by producing Erythropoietin (EPO) 5. Regulate electrolyte balance (Na+, K+, Ca2+) 6. Regulate acid-base balance (by control H+ and HCO3 level). 7. Regulate body fluid Osmolarity (280 mOsm/l) through water balance 8. Enzyme and Hormone production: Renin, Erythropoietin, …. 9. Drug metabolism and chemical Detoxification 10. Glucose production during starvation (gluconeogenesis) 4
  • 5. 1. Cortex- outer layer which contain major portion of nephrons (functional units) 2. Medulla- inner layer which contains  Pyramids-triangular shaped structures,  Renal papilla: is tip of pyramid  Renal calyx – minor and major  Renal pelvis- large area (cavity) which collects urine from calyx (minor & major) and drain it in to Ureters. 5 Internal structure of Kidneys…
  • 6. Renal Blood Circulation  The renal arteries deliver about 21% (1200 ml/min) of the resting cardiac output to the kidneys (Approx. one-fourth)  90% blood flow to cortex  Renal artery branches extensively within the kidney into smaller arteries called afferent arterioles.  Renal blood flow has mainly two purposes: 1. Filtration 2. Renal tissue oxygenation 6
  • 7. Characteristics of Renal Blood Flow 7  In kidney, Two capillary beds 1. Glomerular capillary: High hydrostatic pressure (60 mmHg)→ important for Filtration process 2. Peritubular capillaries (vasa recta): Low hydrostatic pressure (13 mmHg) → importantant for Reabsorption process Peritubular capillaries
  • 8. Nephrons  Nephrons: are structural & functional units of kidneys • There are One million nephron in each kidney • Only 25% of kidney nephrons is needed to adequately maintain all the essential renal excretory and regulatory functions.  Each nephron consists of two parts: 1. Renal Corpuscle - contains glomerular capillaries & Bowman’s capsule - Function: Site of blood plasma filtration. 2. Renal Tubules-Contains tubular structures that extends beyond corpuscle -Function: Reabsorption & Secretion purpose  These tubular structures include; PCT- Proximal Convoluted Tubule, LOH- Loop of Henle, DCT- Distal Convoluted Tubule, CD- Collecting Duct 8
  • 11. Renal Tubule  Proximal convoluted tubule (PCT) – PCT reabsorbs water & solutes from filtrate & secretes substances into it.  Loop of Henle – is U-shaped loop of the renal tubule • Proximal part is similar to the proximal convoluted tubule. • Proximal part is followed by the thin segment & thick segment • Distal convoluted tubule (DCT) – continuation of the loop of Henle and function more in secretion than reabsorption. 11
  • 12. Renal Tubule  Connecting Tubules: The distal portion of the distal convoluted tubule nearer to the collecting ducts.  Two important cell types are found here: 1. Intercalated cells • Cuboidal cells with microvilli. • Function in maintaining the acid-base balance of the body. 2. Principal cells • Cuboidal cells without microvilli. • Help maintain the body’s water and salt balance 12
  • 14. 14
  • 15. 15 Mechanisms of Urine Formation Urine formation and adjustment of blood composition involves three major processes 1. Glomerular Filtration 2. Tubular Reabsorption 3. Tubular Secretion
  • 16. Mechanisms of Urine Formation… 16
  • 18. Glomerular Filtration 18  Glomerular filtration- is the filtration of fluid through the glomerular capillaries in to bowman's capsule  The Glomerular Filtrate contains all plasma components except plasma proteins (albumin, globulin & fibrinogen) and formed elements (blood cells) -RBC, WBC Platelets.  The kidneys filter the body’s entire plasma volume 60 times each day.(3L plasma x 60 times/day= 180L/day).  Plasma proteins (albumin) are not filtered and are used to maintain colloid osmotic pressure of the blood.  Filtration is selective in terms of size but non-selective in terms of usefulness (contains both useful & non-useful).
  • 19. 19 Q. What derives filtration across the walls of glomerular capillaries? Capillary blood pressure favors filtration process. Colloid osmotic pressure & Capsular pressure oppose filtration . Diameter of A.A > E.A→ blood damming up in capillary → ↑CBP
  • 20. Filtration Membrane 20  Fluid filtered from glomerulus into Bowman’s capsule pass through the 3 layers that make up filtration membrane. 1. Endothelial cells with fenestrated capillaries (pores) 2. Basement Membrane 3. Podocyte Cells with filtration slits in inner layer of Bowman’s capsule  This allows huge filtration in the glomerular capillaries except blood cells and plasma proteins.
  • 22. Filtration Membrane… • Filtration membrane is highly permeable to water and small molecules (less than 10.000 MW) • Large molecules (more than 70.000 MW especially proteins are not filtered due to their large size and negative electrical charge because their passage is repulsed by negatively charged glycoproteins present on endothelial pores, basement membrane and podocytes.  Factors that determining the glumerular filterability  Molecular weight  Charges of the molecule 22
  • 23. Glomerular Filtration Rate (GFR) 23 Factors that affect Glomerular Filtration Rate (GFR) ↑ Renal blood flow -- ↑ GFR, b/se it ↑capillary pressure ↑ Plasma protein -- ↓ GFR, b/se it ↑ oncotic pressure. Hemorrhage -- ↓ GFR, b/se it ↓renal blood flow Sympathetic Ns--↓ GFR, b/se afferent arteriole constriction
  • 24. Tubular Reabsorption  Reabsorption-is the process of taking useful substances from the filtrate in to the blood (not to be lost in the urine)  The kidneys produces 180 liters of filtrate per day and normal urinary output in per day 1 to 2 liters.  Approximately 99% of the filtrate is reabsorbed back into the blood in the peritubular capillaries & Only 1% forms urine.  Reabsorbed substances are carried to the venous system → heart  Some reabsorption is passive & most is active transport  Majority of reabsorption takes place in the Proximal tubule.
  • 28. Reabsorption in Proximal Tubule 28 Obligatory water reabsorption in the PCT with Sodium ions (100%)
  • 30. 30 Reabsorption in Ascending LOH (Na-K-2Cl- Cotransport)
  • 33. 33 Role of Aldosterone in Regulation Na+ & K+
  • 34. 34 Reabsorption in Collecting Duct Facultative water reabsorption in the CD by the help of ADH.
  • 35. Role of ADH (Vasopressin) 35 (ADH)
  • 36. 36  Secretion – is the process of adding unwanted substance from blood (peritubular) in to the filtrate for excretion with the urine.  Only 20% of the plasma entering the kidneys is filtered.  Secretion :allows for rapid elimination of substances from the plasma via extraction of the 80% of unfiltered plasma in peritubular capillaries and adding it to the substances already in tubule as result of filtration  Tubular secretion is the reverse of reabsorption process.  Some materials move from the blood (peritubular capillaries) into the renal tubules are: H+, K+ , Creatinine & some drugs like penicilin.  Tubular secretion is an active process. Tubular Secretion
  • 37. 37 Summary of Urine Formation A.LOH- is impermeable to water.
  • 38. 38 Dilute & Concentrated Urine The kidneys can excrete urine of varying concentrations depending on the body’s state of hydration (overhydration and dehydration state).
  • 39. Plasma Clearance  Plasma clearance: The volume of plasma which is cleared from a particular substance by the kidney (in urine).  Plasma clearance expresses the kidneys’ effectiveness in removing various substances from blood to the environment  Clearance is non-invasive way to measure GFR  Inulin clearance and Creatinine clearance: important to measure kidney function by estimating GFR. 39
  • 40. Plasma Clearance…  GFR is an index of kidney function  Measurement of GFR: can be measured by means of the inulin clearance and estimated by means of the creatinine clearance 1. Inulin: a polymer of fructose, precisely measure GFR (Standard)  Freely filtered into the Bowman’s capsule  Not reabsorbed, secreted or metabolized by the nephron  Non-endogenous, has to be infused intravenously 2. Creatinine: endogenously released into plasma by skeletal muscle metabolism, is used to measure GFR (accurate measure GFR)  Not as accurate as inulin as a small quantity is secreted into the proximal tubule.  amount excreted > amount filtered  Reasonably accurate measurement of GFR (easy to monitor) 40
  • 42. Excretion 42 Excretion refers removal of a substance from the body. All plasma constituents filtered or secreted but not reabsorbed remain in the tubules and pass into the renal pelvis to be excreted as urine & eliminated from body.  Urine output=1.5 liters/day).
  • 43. Regulation of Acid-Base Balance by Kidney 43
  • 44. Regulation of Acid-Base Balance (Buffer System)  Buffer is substance that stabilizes [H+] when H+ ions are added or removed from a solution.  They do not eliminate H+ from body – reversibly bind H+ until balance is re- established and form conjugated base or acid. 44
  • 45.  Ureters: Retroperitoneal (behind peritoneum, like kidney) • Tubular organ 25cm long each • Extends from the renal pelvis to the bladder • The smooth muscle in the wall of the ureter contracts in peristaltic waves to propel urine toward the urinary bladder • Gravity also assist to propel urine 45 Transportation, Storage & Elimination of Urine…
  • 46. Urinary bladder • The urinary bladder is a muscular sac which is found behind the pubic bones. • In women, the bladder is inferior to the uterus; • In men, the bladder is superior to the prostate gland. • The bladder is a reservoir for accumulating urine, and it contracts to eliminate urine. 46 Transportation, Storage & Elimination of Urine…
  • 47. 47 • On the floor of the bladder is a triangular area called the trigone, and it does not expand during urinary filling. • The points of the triangle are the openings of the two ureters and that of the urethra • The smooth muscle layer in the wall of the bladder is called the detrusor muscle. • Contraction of dertusor muscles causes urination Transportation, Storage & Elimination of Urine…
  • 48.  Urethra • Transports urine from urinary bladder to outside • Its wall contains mucus secreting urethral glands  Parts of male urethra 1. Prostatic urethra 2. Membranous urethra 3. Penile urethra • Urethral orifice is on glans penis. 48 Transportation, Storage & Elimination of Urine… Q. What is prostate hypertrophy & its effect on urination? Impede urine flow or ↑urine flow ?
  • 49. Micturition Reflex 49 Micturition (Urination ) is the process of bladder emptying. 2 mechanisms: the Micturition reflex and Voluntary control
  • 50. Renal Failure 1. Acute: Sudden onset, rapid reduction in urine output - usually reversible 2. Chronic: Progressive, not reversible Up to 75% function can be lost before it is noticeable. Generalized Site of Disease: 1. Prerenal: Inadequate renal blood flow 2. Intrarenal: Nephron damage 3. Postrenal: Obstruction, Structural defects 50