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Renal Functions
Satriyo Dwi Suryantoro
Disampaikan pada Guest Lecture
Smu Muhammadiyah 2 Surabaya
7 November 2022
Structure of the kidney
Cortex – the outer layer of the kidney
Medulla – the inner layer of the kidney
LOBES – 8-10 Interstitium
Pyramid – the part of medullary tissue,
plus the cortical tissue
Papilla – the tip of the medullary
pyramid
Minor calyx - a cup-shaped drain that
urine is brought to from the renal papillae.
Urine passes from the minor calyx to the
major calyx and than to the pelvis
The main function of the kidneys
URINE FORMATION
• Regulation of acid - base balance
• Gluconeogenesis
NEPHRON
The functional unit of renal structure and
function
Renal tubule
Renal corpuscle
Each human kidney contains about one million nephrons
The kidney cannot regenerate new nephrons
Nephron = renal corpuscle + renal tubules
The place of
ultrafiltrate production
The place of
tubular reabsorption
and tubular secretion
URINE FORMATION
Types of nephrons:
Cortical and juxtamedullary nephrons
Vasa recta reach deep into
the inner medulla and they
are in close contact with
each other, run down
around the loop of Henle
The main function of
vasa recta:
supply of oxygene and
nutrients to nephrons,
deliver substances to the
nephrons for secretion,
reabsorption water,
concentrating and and
diluting urine
Renal corpuscle
1 Bowman’s capsule – a membranous
double-walled structure around the
glomerulus of each nephron
2 Glomerulus – a taft of fenestrated
capillaries
Glomerulus
The glomerulus contains a network
of branching capillaries that have
high hydrostatic pressure
(60 mm Hg)
They are covered by the inner layer
of Bowman’s capsule
Fenestrated endothelium
characterized by the presence of
circular fenestrae or pores that
penetrate the endothelium; these
pores may be closed by a very
thin diaphragm
Renal corpuscle - ultrastructure
The filtration membrane
To be filtered a substance must
pass through:
1 Fenestrated endothelium the pores
between the endothelial cells of the
glomerular capillary
2 Basement membrane - an acellular
structure
3 Foot of the podocytes -the filtration
slits between of the inner layer
of Bowman’s capsule
Renal tubule
1. Proximal convoluted tubule
Regarding ultrastructure, it can be divided into
three segments, S1, S2, and S3
Cells have microvilli on their luminal surface – border brush
Proximal tubules have a high capacity for active and passive
reabsorption. Their cells have large numer of mitochondria
High metabolic activity
Finally hypoosmotic fluid
Renal tubule
-Ascending limb of loop of Henle
The ascending limb is virtually
impermeable to water
Reabsorption water and sodium chloride from the tubular fluid
Finally hypoosmotic fluid
2. The loop of Henle
- Descending limb of loop of Henle
The descending limb is highly
permeable to water
Thick ascending segment
Thin ascending segment
Renal tubule
3. Distal Convoluted tubule
- early DCT
- late DCT
The distal tubules of several nephrons form a collecting duct
that passes down into the medulla
4. Collecting duct
- Cortical collecting duct
- Medullary collecting duct
Regulation of water, electrolyte and acid – base balance
Osmolality of tubular fluid depends on AHD
Renal processes involved in urine formation:
• Glomerular Filtration: filtering of
blood into Bowman’s space forming
the ultrafiltrate
• Tubular Reabsorption: absorption
of substances needed by body from
tubule to blood
• Tubular Secretion: secretion of
substances to be eliminated from the
body into the tubule from the blood
• Excretion: elimination of
substances via the urine
Urine formation
Ultrafiltrate Tubular fluid Urine
Daily totals
Glomerulat filtration - elimination
 Filtration ~ 180 liters filtered out/day
(125 mL/min)
 Reabsorption ~ 179 liters returned to
the blood/day
 ~ 1 liter excreted as urine/day
(0.78 mL/min)
About 99% of filtrate is reabsorbed
All processes occuring in tubules reduce the
volume and change the composition of
glomerular filtrate and eventually form urine
The glomerular membrane has strong negative electrical
charges associated with proteoglycans
Negatively charged large molecules are filtered less
easily than positively charged molecules of equal
molecular size
The glomerular filtration barrier
The glomerular barrier selects for two basic molecular
features: size and charge.As the molecular weight of a
molecule increases, its capacity for filtration
progressively and rapidly declines
Furthermore, for any given sized molecules, its capacity
for filtration progressively and rapidly declines as its
charge becomes more negative
Because plasma proteins are typically large and
negatively charged, they are almost totally prevented
from crossing the glomerular barrier
Glomerular Filtration Rate (GFR)
Glomerular filtration rate (GFR) describes
the filtration process
GFR is the volume of fluid filtered from
the glomerular capillaries into
the Bowman's capsule per unit time
ml/min
There are several different techniques
used to calculate or estimate the GFR
Determinants of the glomerular filtration rate (GFR)
GFR = Kf x Net filtration pressure
The filtration coefficient (Kf ) is a measure
GFR as a crucial parameter of renal function
- Glomerular hydrostatic pressure (PG) -
- Bowman’s capsule hydrostatic pressure (PB) -
- Glomerular colloid osmotic pressure (πG) -
- Bowman’s capsule colloid osmotic pressure (πB)
promotes filtration
opposes filtration
opposes filtration
- promotes filtration
NFP= 60 – 18 – 32 + 0 = +10 mm Hg
The forces create net filtration pressure
of the product of the hydraulic conductivity
and surface area of the glomerular capillaries
X
The net filtration pressure (NFP) represents the
sum of the hydrostatic and colloid osmotic forces
thateither favor or oppose filtration across the
glomerular capillaries
Glomerular filtration rate (GFR)
When Cx ≈ GFR ?
Any substance that meets the following criteria can serve as an appropriate
(for clearance!!!) marker for the measurement of GFR
Inulin clearance (Cin) equals the glomerular filtration rate (GFR)
Inulin meets the following criteria:
- freely filtered
- not reabsorbed or secreted
- not synthesized, destroyed, or stored
- nontoxic
- its concentration in plasma and urine can be determined by simple analysis
Inulin is
a fructose
polymer, stored in
some plants as an
alternative food
reserve to starch
(eg. chckory)
Cin = GFR
Inulin clearance is the gold standard for measuring GFR
All filtered inulin is excreted
Since the volume of plasma cleared of inulin is the
volume filtered, the inulin clearance equals the GFR.
125 ml/min of inulin passes into the urine
How to measure Cinulin?
Inulin is not commonly used in the clinical practice:
- infused intravenously
- the bladder is usually catheterized
- inconvenient - to maintain a constant plasma concentration
inulin must be infused continuously throughout measurement
Since inulin is an exogenous substance it is only used for research
purposes and not as a clinical test
Is there any endogenous substance that has similar characteristics to inulin?
Inulin clearance equals the glomerular filtration rate (GFR)
Creatinine is a breakdown product of creatine phosphate in muscle, and is usually produced
at a constant rate by the body (depending on muscle mass)
Exogenous substance Endogenous substance
Creatinine is slightly
secreted
Creatinine
The endogenous creatinine clearance (CCR)
- An endogenous product of muscle metabolism
- Near - constant production
- Small molecule (114 kDa)
- Concentration depending on muscle mass
- Inversely proportional to GFR
Freely filtered, not reabsorbed but SLIGHTLY SECRETED
CCR ≈ GFR The measurement of creatinine clearance is a valuable
determinator of GFR but NOT in routine practice.
Relationship between estimated glomerular filtration rate (eGFR) and
plasma creatinine (SCr)
The GFR must decline substantially
before an increase in the SCr can be
detected in a clinical setting
eGFR can decrease by 50% before
plasma creatinine concentration rises
beyond the normal range
SCR is a weak indicator, and not sensitive
parameter in the early stage of renel
kidney disease
e
An alternative approach to determine the GFR
in clinical practice is to derive an estimated GFR (eGFR)
from the plasma creatinine concentration (Pcr)
Estimation - a rough calculation of the value, number, quantity, or extent of something.
Several empirical equations have beed developed that allow
physicians to estimate GFR from
plasma creatinine concentration, body weigth, age, and gender
Estimation of plasma creatinine concentration
to the GFR using some equation
Estimation of plasma creatinine concentration
to the GFR using some equation
eGFR
ACUTE KIDNEY INJURY :
DEFINITION & STAGING
Acute Kidney Injury & Acute Tubular Necrosis
“
“
any of the following :
• increase in Serum Creatinine by > 0.3 mg/dl within 48 hours
OR
• increase in Serum Creatinine to > 1.5 times baseline, which is
known or presumed to have occurred within prior 7 days;
OR
• urine volume < 0.5 ml/kg/h for 6 hours
staging of AKI
STAGE Serum Creatinine Urine Output
1 1.5 – 1.9 times baseline
OR
> 0.3 mg/dL increase
< 0.5 ml/kg/h for 6-12 hours
2 2.0 – 2.9 times baseline < 0.5 ml/kg/h for > 12 hours
3 3.0 times baseline
OR
increase in serum creatinine to > 4.0 mg/dl
OR
initiation of RRT
OR
in pts < 18 years, decrease in eGFR to
< 35 ml/min/1.73 m2
< 0.3 ml/kg/h for > 24 hours
OR
anuria for > 12 hours
Renal interstitium
Renal interstitium is a complex structure divided into cortical and
medullar part
It serves as an environment for blood vessels and tubules and
therefore it is known as a key coordinating element
The interstitial compartment cells: non–hormone-producing
fibroblasts , microvessels, perivascular cells, renin-producing
perivascular cells, juxtaglomerular cells, and erythropoietin
(Epo)-producing fibroblasts
Secretion of erythropoietin (EPO)
Production of renin
Regulation of calcitriol production
Glucose synthesis (gluconeogenesis)
The interstitium, located between tubules is barely visible

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Fisiologi Renal Smamda 7 November 2022.pptx

  • 1. Renal Functions Satriyo Dwi Suryantoro Disampaikan pada Guest Lecture Smu Muhammadiyah 2 Surabaya 7 November 2022
  • 2.
  • 3.
  • 4. Structure of the kidney Cortex – the outer layer of the kidney Medulla – the inner layer of the kidney LOBES – 8-10 Interstitium Pyramid – the part of medullary tissue, plus the cortical tissue Papilla – the tip of the medullary pyramid Minor calyx - a cup-shaped drain that urine is brought to from the renal papillae. Urine passes from the minor calyx to the major calyx and than to the pelvis
  • 5. The main function of the kidneys URINE FORMATION • Regulation of acid - base balance • Gluconeogenesis
  • 6. NEPHRON The functional unit of renal structure and function Renal tubule Renal corpuscle Each human kidney contains about one million nephrons The kidney cannot regenerate new nephrons
  • 7. Nephron = renal corpuscle + renal tubules The place of ultrafiltrate production The place of tubular reabsorption and tubular secretion URINE FORMATION
  • 8. Types of nephrons: Cortical and juxtamedullary nephrons Vasa recta reach deep into the inner medulla and they are in close contact with each other, run down around the loop of Henle The main function of vasa recta: supply of oxygene and nutrients to nephrons, deliver substances to the nephrons for secretion, reabsorption water, concentrating and and diluting urine
  • 9. Renal corpuscle 1 Bowman’s capsule – a membranous double-walled structure around the glomerulus of each nephron 2 Glomerulus – a taft of fenestrated capillaries
  • 10. Glomerulus The glomerulus contains a network of branching capillaries that have high hydrostatic pressure (60 mm Hg) They are covered by the inner layer of Bowman’s capsule Fenestrated endothelium characterized by the presence of circular fenestrae or pores that penetrate the endothelium; these pores may be closed by a very thin diaphragm
  • 11. Renal corpuscle - ultrastructure The filtration membrane To be filtered a substance must pass through: 1 Fenestrated endothelium the pores between the endothelial cells of the glomerular capillary 2 Basement membrane - an acellular structure 3 Foot of the podocytes -the filtration slits between of the inner layer of Bowman’s capsule
  • 12. Renal tubule 1. Proximal convoluted tubule Regarding ultrastructure, it can be divided into three segments, S1, S2, and S3 Cells have microvilli on their luminal surface – border brush Proximal tubules have a high capacity for active and passive reabsorption. Their cells have large numer of mitochondria High metabolic activity Finally hypoosmotic fluid
  • 13. Renal tubule -Ascending limb of loop of Henle The ascending limb is virtually impermeable to water Reabsorption water and sodium chloride from the tubular fluid Finally hypoosmotic fluid 2. The loop of Henle - Descending limb of loop of Henle The descending limb is highly permeable to water Thick ascending segment Thin ascending segment
  • 14. Renal tubule 3. Distal Convoluted tubule - early DCT - late DCT The distal tubules of several nephrons form a collecting duct that passes down into the medulla 4. Collecting duct - Cortical collecting duct - Medullary collecting duct Regulation of water, electrolyte and acid – base balance Osmolality of tubular fluid depends on AHD
  • 15. Renal processes involved in urine formation: • Glomerular Filtration: filtering of blood into Bowman’s space forming the ultrafiltrate • Tubular Reabsorption: absorption of substances needed by body from tubule to blood • Tubular Secretion: secretion of substances to be eliminated from the body into the tubule from the blood • Excretion: elimination of substances via the urine
  • 17. Daily totals Glomerulat filtration - elimination  Filtration ~ 180 liters filtered out/day (125 mL/min)  Reabsorption ~ 179 liters returned to the blood/day  ~ 1 liter excreted as urine/day (0.78 mL/min) About 99% of filtrate is reabsorbed All processes occuring in tubules reduce the volume and change the composition of glomerular filtrate and eventually form urine
  • 18. The glomerular membrane has strong negative electrical charges associated with proteoglycans Negatively charged large molecules are filtered less easily than positively charged molecules of equal molecular size The glomerular filtration barrier The glomerular barrier selects for two basic molecular features: size and charge.As the molecular weight of a molecule increases, its capacity for filtration progressively and rapidly declines Furthermore, for any given sized molecules, its capacity for filtration progressively and rapidly declines as its charge becomes more negative Because plasma proteins are typically large and negatively charged, they are almost totally prevented from crossing the glomerular barrier
  • 19. Glomerular Filtration Rate (GFR) Glomerular filtration rate (GFR) describes the filtration process GFR is the volume of fluid filtered from the glomerular capillaries into the Bowman's capsule per unit time ml/min There are several different techniques used to calculate or estimate the GFR
  • 20. Determinants of the glomerular filtration rate (GFR) GFR = Kf x Net filtration pressure The filtration coefficient (Kf ) is a measure GFR as a crucial parameter of renal function - Glomerular hydrostatic pressure (PG) - - Bowman’s capsule hydrostatic pressure (PB) - - Glomerular colloid osmotic pressure (πG) - - Bowman’s capsule colloid osmotic pressure (πB) promotes filtration opposes filtration opposes filtration - promotes filtration NFP= 60 – 18 – 32 + 0 = +10 mm Hg The forces create net filtration pressure of the product of the hydraulic conductivity and surface area of the glomerular capillaries X The net filtration pressure (NFP) represents the sum of the hydrostatic and colloid osmotic forces thateither favor or oppose filtration across the glomerular capillaries
  • 21. Glomerular filtration rate (GFR) When Cx ≈ GFR ? Any substance that meets the following criteria can serve as an appropriate (for clearance!!!) marker for the measurement of GFR
  • 22. Inulin clearance (Cin) equals the glomerular filtration rate (GFR) Inulin meets the following criteria: - freely filtered - not reabsorbed or secreted - not synthesized, destroyed, or stored - nontoxic - its concentration in plasma and urine can be determined by simple analysis Inulin is a fructose polymer, stored in some plants as an alternative food reserve to starch (eg. chckory) Cin = GFR
  • 23. Inulin clearance is the gold standard for measuring GFR All filtered inulin is excreted Since the volume of plasma cleared of inulin is the volume filtered, the inulin clearance equals the GFR. 125 ml/min of inulin passes into the urine How to measure Cinulin?
  • 24. Inulin is not commonly used in the clinical practice: - infused intravenously - the bladder is usually catheterized - inconvenient - to maintain a constant plasma concentration inulin must be infused continuously throughout measurement Since inulin is an exogenous substance it is only used for research purposes and not as a clinical test Is there any endogenous substance that has similar characteristics to inulin? Inulin clearance equals the glomerular filtration rate (GFR)
  • 25. Creatinine is a breakdown product of creatine phosphate in muscle, and is usually produced at a constant rate by the body (depending on muscle mass) Exogenous substance Endogenous substance Creatinine is slightly secreted Creatinine
  • 26. The endogenous creatinine clearance (CCR) - An endogenous product of muscle metabolism - Near - constant production - Small molecule (114 kDa) - Concentration depending on muscle mass - Inversely proportional to GFR Freely filtered, not reabsorbed but SLIGHTLY SECRETED CCR ≈ GFR The measurement of creatinine clearance is a valuable determinator of GFR but NOT in routine practice.
  • 27. Relationship between estimated glomerular filtration rate (eGFR) and plasma creatinine (SCr) The GFR must decline substantially before an increase in the SCr can be detected in a clinical setting eGFR can decrease by 50% before plasma creatinine concentration rises beyond the normal range SCR is a weak indicator, and not sensitive parameter in the early stage of renel kidney disease e
  • 28. An alternative approach to determine the GFR in clinical practice is to derive an estimated GFR (eGFR) from the plasma creatinine concentration (Pcr) Estimation - a rough calculation of the value, number, quantity, or extent of something. Several empirical equations have beed developed that allow physicians to estimate GFR from plasma creatinine concentration, body weigth, age, and gender Estimation of plasma creatinine concentration to the GFR using some equation
  • 29. Estimation of plasma creatinine concentration to the GFR using some equation eGFR
  • 30. ACUTE KIDNEY INJURY : DEFINITION & STAGING Acute Kidney Injury & Acute Tubular Necrosis
  • 31. “ “ any of the following : • increase in Serum Creatinine by > 0.3 mg/dl within 48 hours OR • increase in Serum Creatinine to > 1.5 times baseline, which is known or presumed to have occurred within prior 7 days; OR • urine volume < 0.5 ml/kg/h for 6 hours
  • 32. staging of AKI STAGE Serum Creatinine Urine Output 1 1.5 – 1.9 times baseline OR > 0.3 mg/dL increase < 0.5 ml/kg/h for 6-12 hours 2 2.0 – 2.9 times baseline < 0.5 ml/kg/h for > 12 hours 3 3.0 times baseline OR increase in serum creatinine to > 4.0 mg/dl OR initiation of RRT OR in pts < 18 years, decrease in eGFR to < 35 ml/min/1.73 m2 < 0.3 ml/kg/h for > 24 hours OR anuria for > 12 hours
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  • 37. Renal interstitium Renal interstitium is a complex structure divided into cortical and medullar part It serves as an environment for blood vessels and tubules and therefore it is known as a key coordinating element The interstitial compartment cells: non–hormone-producing fibroblasts , microvessels, perivascular cells, renin-producing perivascular cells, juxtaglomerular cells, and erythropoietin (Epo)-producing fibroblasts Secretion of erythropoietin (EPO) Production of renin Regulation of calcitriol production Glucose synthesis (gluconeogenesis) The interstitium, located between tubules is barely visible