Transcript glomerular filteration

GLOMERULAR FILTERATION
Dr.Mohammed Sharique Ahmed Quadri
Assistant prof. Physiology
Al Maarefa College
OBJECTIVES
• Identify three basic processes involved in urine formation;
glomerular filtration, tubular reabsorption and tubular
secretion
• Define GFR and quote normal value in men and women
• Describe the composition of the glomerular filtrate
• Detect the structural & functional peculiarities of the
glomerular filtration membrane
• Outline the factors controlling GFR
• Given capillary and Bowman’s capsule hydrostatic and
oncotic pressures calculate the net filtration pressure.
• Correlate between net filtration pressure along glomerulus
and plasma flow
• List the characteristics that a compound must have before
it can be used for measuring GFR e.g. Inulin, creatinine etc.
• Given the data, calculate GFR .
Basic Renal Processes
• Glomerular filtration
• Tubular reabsorption
• Tubular secretion
Urine results from these
three processes.
Glomerular filtration
• Is the first step in urine
formation.
• Definition:
Glomerular
filtration is the transfer of
fluid and solutes from the
glomerular capillaries along a
pressure
gradient
into
Bowman's capsule.
Composition of the Glomerular Filtrate
• It is the fluid within the Bowman’s capsule that is
essentially cell-free and protein-free and contains
crystalloids in virtually the same concentrations as in
the plasma.
• It is free from:
– Blood cells
– Protein
– Protein-bound molecules
(calcium, fatty aids, amino acids)
Glomerular Filtration
• Fluid filtered pass through three layers of the
glomerular membrane
– Glomerular capillary wall
• Single layer of endothelial cells
• More permeable to water and solutes than capillaries
elsewhere in the body
– Basement membrane
• Acellular gelatinous layer
• Composed of collagen and glycoproteins
– Inner layer of Bowman’s capsule
• Consists of podocytes that encircle the glomerulus tuft
Glomerular Capillary Filtration Barrier
 Endothelium (fenestrated)
 Basement Membrane negatively
charged, restriction site for proteins
 Epithelial Cells, restriction site for
proteins. Characterized by foot-like
processes (podocytes).
Filtration
• Despite the three layers of the barrier, the glomerulus filters
several hundred times as much water and solutes as the usual
capillary membrane.
• Even with this high rate of filtration, the glomerular capillary
membrane normally prevents filtration of plasma proteins.
Glomerular Capillary Membrane
Filterability depends on:
Size of the molecule
– the pores of the glomerular membrane are about 8
nanometers (80 angstroms)
Electrical Charge of the molecule
– positively charged molecules are filtered much more easily
than negatively charged molecules of equal molecular size.
– the negative charges of the basement membrane and the
podocytes provide an important means for restricting
negatively charged molecules, including the plasma
proteins.
– Diameter of albumin is only about 6 nanometers, but
negatively charged.
Clinical Significance of
Proteinuria
• Early detection of renal disease in at-risk patients
- Hypertension: Hypertensive renal disease
- Diabetes: Diabetic nephropathy
- Pregnancy: gestational proteinuric hypertension
(pre-eclampsia)
- annual “check-up”: renal disease can be silent
• Assessment and monitoring of known renal
disease
Microalbuminuria
• Definition: urine excretion of > 25-30 but
< 150mg albumin per day
• Causes: early diabetes, hypertension
• Prognostic Value: diabetic patients with
microalbuminuria are 10-20 fold more
likely to develop persistent proteinuria
Glomerular Filtration Rate (GFR)
GFR: The volume of plasma filtered from both kidneys
per minute.
GFR = 125 ml/min = 180 liters/day
Plasma volume is filtered 60 times per day
GFR= Filtration Coefficient (Kf) x Net Filtration Pressure(NFP)
Factors Affecting GFR
Filtration
Coefficient (Kf)
Net Filtration
Pressure(NFP)
Filtration coefficient
• Filtration coefficient (Kf): A measure of the
product of the hydraulic conductivity (water
permeability) and filtering surface area of the
capillaries.
• glomerular capillary filtration coefficient =
12.5 ml/min per mmHg, or
4.2 ml/min per mmHg/ 100gm
• (400 x greater than in tissues such a muscle)
Increased Glomerular Capillary
Filtration Coefficient (Kf) Increases GFR
• Normally not highly variable
• Kf reduces by reducing the number of functional
glomerulus (decrease surface area) or by increasing
the thickness BM (reducing its hydraulic
conductivity).
• Diseases that can reduce Kf and eventually GFR
- Chronic hypertension
- Diabetes mellitus
- Glomerulonephritis
Forces determining Net Filtration
Pressure (NFP)
• Three physical forces
involved
– Glomerular capillary
hydrostatic pressure
– Plasma-colloid osmotic
osmotic pressure
– Bowman’s capsule
hydrostatic pressure
blood
hydrostatic
1 GLOMERULAR BLOOD
HYDROSTATIC PRESSURE
(GBHP) = 55 mmHg
2 CAPSULAR HYDROSTATIC
PRESSURE (CHP) = 15 mmHg
3 BLOOD COLLOID
OSMOTIC PRESSURE
(BCOP) = 30 mmHg
Afferent arteriole
Proximal convoluted tubule
Efferent
arteriole
NET FILTRATION PRESSURE (NFP)
=GBHP – CHP – BCOP
= 55 mmHg 15 mmHg 30 mmHg
= 10 mmHg
Glomerular
(Bowman's)
capsule
Capsular
space
Net (effective) Filtration Pressure (NFP)
• Definition: = NFP is an algebraic sum of opposing
hydrostatic and osmotic forces acting across the
capillary
• NFP = forces inducing filtration - forces opposing filtration
• NFP =
–
–
–
–
( PGC + BC ) -
( PBC + GC )
BC
PGC Glomerular hydrostatic pressure
GC Glomerular oncotic pressure
PBC
PBC Bowman’s capsule hydrostatic pressure
 BC Bowman’s capsule oncotic pressure
• NB: as there is virtually no protein, BC ~ 0,
• therefore
NFP = PGC - (PBC + GC)
PGC
GC
Glomerular Filtration Rate
• Net filtration pressure = glomerular capillary blood
pressure – (plasma-colloid osmotic pressure +
Bowman’s capsule hydrostatic pressure)
For example:
55 mm Hg – (30 mm Hg + 15 mm Hg) = 10 mm Hg
• Glomerular filtration rate (GFR)
– Depends on
• Net filtration pressure
• How much glomerular surface area is available for penetration
• How permeable the glomerular membrane is
Unregulated influences on the GFR
Increased Bowman’s Capsule Hydrostatic Pressure
(PBc) Decreases GFR
• Do not serve as physiological regulator of GFR
• Increase of PBc can be caused by
• Tubular Obstruction
• kidney stones
• tubular necrosis
• Urinary tract obstruction
• Prostatic enlargement
Unregulated influences on the GFR
plasma colloid osmotic pressure
• Do not serve as physiological regulator of GFR
• Plasma-colloid osmotic pressure
• Severely burned patient ↑ GFR
• Dehydrating diarrhea ↓ GFR
Glomerular Filtration Rate
• Controlled adjustments in GFR
– Glomerular capillary hdrostatic pressure can be
controlled to adjust GFR to suit the body’s needs
– Two major control mechanisms
• Extrinsic sympathetic control -by adjusting the
constriction of afferent/efferent arterioles
– Mediated by sympathetic nervous system input to afferent
arterioles
– Baroreceptor reflex
• Autoregulation (aimed at preventing spontaneous
changes in GFR)
– Myogenic mechanism
– Tubuloglomerular feedback (TGF)
Adjustments of Afferent
Arteriole Caliber to Alter
The GFR
Baroreceptor Reflex
Influence on the GFR
Calculation of Glomerular Filtration
Rate (GFR)
•GFR = Filtration Coefficient (Kf ) x Net Filtration Pressure (NFP)
• GFR =
12.5 x 10 = 125 ml/min = 180 liters/day
• GFR in females is less (110 ml/min)
• Plasma volume is filtered 60 times per day
Autoregulation
The major function of autoregulation in the kidneys is to
maintain a relatively constant GFR and renal blood flow
despite considerable arterial pressure fluctuations that
can occur.
Autoregulation:
• Myogenic autoregulation
• Tubuloglomerular feedback
Myogenic Mechanism
Vascular smooth muscle contraction in response to increased stretch
Arterial
Pressure
Stretch of
Blood Vessel
Cell Ca++
Permeability
Blood Flow
Vascular
Resistance
Intracell. Ca++
Macula Densa Feedback
(Tubuloglomerular feedback)
GFR
Distal NaCl
Delivery
Macula Densa NaCl Reabsorption
(macula densa feedback)
Afferent Arteriolar Resistance
GFR (return toward normal)
Macula Densa feedback mechanism for GFR
autoregulation
What is a Glomerular Filtration Fraction?
• The Filtration Fraction (FF) is the ratio of the
GFR to the renal plasma flow (GFR/TRPF).
• Renal blood flow = 1.1 L/min
• 20-25% of total cardiac output (5 L/min).
• Of the 625 ml of plasma enters the glomeruli via the
afferent, 125 (the GFR) filters in the Bowman’s
capsule, the remaining passing via efferent arterioles
into the peritubular capillaries
• Filtration fraction = (GFR/TRPF) = 0.2
• So, GFR is About 20% of the Renal Plasma Flow
The filtration fraction
The Filtration
Fraction (FF)
is the ratio of the
GFR to the renal
plasma flow =
(GFR/TRPF).
References
• Human physiology by Lauralee Sherwood,
seventh edition
• Text book physiology by Guyton &Hall,11th
edition
• Text book of physiology by Linda .s
contanzo,third edition