Renal-2015 pharmacy

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RENAL PHYSIOLOGY
DR SYED SHAHID HABIB
MBBS DSDM FCPS
Associate Professor
Dept. of Physiology
College of Medicine & KKUH
Renal Physiology
1)
2)
3)
4)
5)
Introduction
Glomerular Filtration
Tubular Processing
Urine Concentrating Mechanism
Micturition
PHYSIOLOGIC ANATOMY OF KIDNEYS
• Size Clenched Fist
• Weight 150 grams
FUNCTIONS OF THE KIDNEY
1. Regulation of water (extracellular
fluid volume)
2. Maintenance of electrolyte
balance (Na+, K+, HCO3-, Ca++)
3. Regulation of arterial pressure
4. Regulation of blood pH
FUNCTIONS OF THE KIDNEY (Cont.)
5. Excretion of wastes (creatinine, urea,
benzoate, penicillin, saccharin)
6. Secretion, metabolism, and excretion
of hormones
Hormone production (Erythropoietin,
Renin)
Activation of Vitmain D
7. Gluconeogenesis
PHYSIOLOGIC ANATOMY OF KIDNEYS
NEPHRON
• FUNCTIONAL UNIT OF THE KIDNEY
• CONSISTS OF:
– BLOOD VESSELS:
– URINARY TUBULES:
• BOWMAN’S CAPSULE
• PROXIMAL CONVOLUTED
TUBULE
• LOUP OF HENLE
• DISTAL CONVOLUTED TUBULE
• COLLECTING DUCT
PARTS OF NEPHRON
NEPHRON TYPES
Superficial (cortical) [85 %]
o Capable of forming dilute urine
Juxtamedullary [15 %]
o Capable of forming concentrated
(> 300 mOsm/kg) urine
NEPHRON TYPES
Cortical and
Juxtamedullary
Nephrons
1-2 % Blood
Flows
Through
Juxta Medullary
Nephrons
Originates
in outer 2/3
of cortex.
Originates
in inner 1/3
of cortex.
Renal blood flow
• About 21% of cardiac output
• Renal circulation is characterized by:
1. High rate of blood flow.
2. Presence of two capillary beds:
a. glomerular : they filter large amounts of
fluid and solutes.
b. peritubular capillaries: absorption of most
of filtered fluid.
RENAL BLOOD VESSELS
• AFFERENT ARTERIOLE:
– DELIVERS BLOOD INTO THE GLOMERULI.
• GLOMERULI:
– CAPILLARY NETWORK THAT PRODUCES
FILTRATE THAT ENTERS THE URINARY TUBULES.
• EFFERENT ARTERIOLE:
– DELIVERS BLOOD FROM GLOMERULI TO
PERITUBULAR CAPILLARIES.
• PERITUBULAR CAPILLARIES:
– VASA RECTA.
BOWMAN’S CAPSULE
4 RENAL
1. Filtration
PROCESSES
2. Reabsorption
1. Filtration
2. Reabsorption
3. Secretion
4. Excretion
3. Secretion
4. Excretion
Urinary Excretion Rate = Filtration Rate – Reabsorption Rate + Secretion Rate
Renal Corpuscle
Glomerular filtrate collects in capsular space, flows
into renal tubule
FILTRATION MEMBRANE
4-8 nm size particles can be filtered easily
2. Basement Membrane
Filtration
1. Endothelium
Endothelium of
Glomerular Capillaries
3. Podocyte
Glomerular membrane
• 1. endothelium of glomerular capillaries
(Fenestra)
• 2. Basement membrane prevent passage of
molecules of molecular weight more than
70,000) (- ve charge)
(albumin and larger are held back, so normally no
protein in urine).
• 3. Podocytes secrete (slit pores)
Glomerular membrane
RENAL PHYSIOLOGY
GLOMERULAR FILTRATION
FILTRATION AND OSMOSIS
At a molecular level, filtration is the bulk
flow of fluid through a membrane or other
barrier that selectively impedes the
movement of some molecules, the largest
being impeded most. This process is
sometimes called ULTRAFILTRATION.
GLOMERULAR FILTRATE
GLOMERULAR FILTRATE CONTAINS ALL CONSTITUENTS
OF PLASMA IN SAME CONCENTRATION
EXCEPT BLOOD CELLS AND PLASMA PROTEINS
Renal blood flow
• Normal renal blood flow = 1200 ml/min
….1/5th cardiac output.
•
•
•
•
GFR=125ML/MIN
OR 125X60X24=180000=180L/DAY
Normal Urinary Output=1.5 L/day
Daily Reabsorption 180-1.5=178.5
L/day
• Percent Reabsorbed =
178.5x100/180=99.2%
• Percent Excreted = 100-99.2=0.8%
(Less than 1 % becomes urine)
• Obligatory Urinary Output=0.50.6L
Glomerular Filtration Rate (GFR)
• Defined as:
The volume of filtrate produced by both kidneys
per min
– Averages 125 ml/min
– Totals about 180L/day (45 gallons)
• 99% of filtrate reabsorbed, 1 to 2 L urine excreted or
death would occur from water lost through urination
• GFR = NFP x Kf  125 ml/min or 180 L/day
• GFR = 10 X 12.5 = 125 ml/min
17-24
Forces controlling GFR &Net Filtration
Pressure (NFP)
DETERMINANTS OF GFR
Forces Favoring Filtration (mm Hg)
Glomerular hydrostatic pressure
60
Forces Opposing Filtration (mm Hg)
Bowman's capsule hydrostatic pressure
18
Glomerular capillary colloid osmotic
32
pressure
Net Filtration Pressure = 60 – (18 + 32) = +10 mm Hg
CONTROL OF GFR
GFR = Kf x [(PG-PB)-(G- B)]
GFR = Kf x [(60-18)-(32- 0)]
(1) Hydrostatic pressure inside the glomerular capillaries
(glomerular hydrostatic pressure, PG), which promotes
filtration
(2) The hydrostatic pressure in bowman's capsule (PB) outside
the capillaries, which opposes filtration
(3) The colloid osmotic pressure of the glomerular capillary
plasma proteins (πg), which opposes filtration
(4) The colloid osmotic pressure of the proteins in bowman's
capsule (πb), which promotes filtration
Forces determining GFR
• Increased Bowman’s capsule pressure
decreases GFR. It can happen in urinary
obstruction e.g. stones , tumors..
• Increased glomerular capillary colloid osmotic
pressure decreases GFR.
• Increased glomerular capillary hydrostatic
pressure increases GFR. This pressure is
affected by:
- ABP.
- Afferent arteriolar resistance.
- Efferent arteriolar resistance
Physiological control of GFR
• GFR controlled by adjusting glomerular
hydrostatic pr and glomerular capillary
colloid osmotic pr
– Sympathetic control
– Hormonal mechanism: renin and angiotensin
– Intrinsic factors (autoregulation)
Sympathetic Control of GFR
• When the sympathetic nervous system is at rest:
– Renal blood vessels are maximally dilated
• Under stress:
– Norepinephrine is released by the sympathetic
nervous system
– Epinephrine is released by the adrenal medulla
– Afferent arterioles constrict and filtration is
inhibited--- ↓ PG GFR ↓
AUTOREGULATION
OF GFR
• GFR remains
constant over
a large range
of values of BP
• 75-160 mmHg
Autoregulation
1. Myogenic
2. Tubuloglomerular Feedback (juxtaglomerular
apparatus)
Juxtaglomerular Apparatus
- vasomotion
- monitor salinity
Hormonal Control of GFR
-efferent arterioles
Effects of Angiotensin II
Physical
Determinants* Physiologic/Pathophysiologic Causes
↓ Kf → ↓ GFR
Renal disease, diabetes mellitus, hypertension
↑ PB → ↓ GFR
Urinary tract obstruction (e.g., kidney stones)
↑ πG → ↓ GFR
↓ Renal blood flow, increased plasma proteins
↓ PG → ↓ GFR
↓ AP → ↓ PG
↓ Arterial pressure (has only small effect due to
autoregulation)
↓ RE → ↓ PG
↓ Angiotensin II (drugs that block angiotensin II formation)
↑ RA → ↓ PG
↑ Sympathetic activity, vasoconstrictor hormones (e.g.,
norepinephrine, endothelin)
Kf, glomerular filtration coefficient; PB, Bowman's capsule
hydrostatic pressure; πG, glomerular capillary colloid osmotic
pressure; PG, glomerular capillary hydrostatic pressure; AP,
systemic arterial pressure; RE, efferent arteriolar resistance; RA,
afferent arteriolar resistance.
* Opposite changes in the determinants usually increase GFR.
Measurement of GFR
• Creatinine clearance
• Inulin clearance
• Clearance (ml/min)=( U* x V*)/P*
inulin
urea
gluc
Creat
Urinary Excretion Rate = Filtration Rate – Reabsorption Rate + Secretion Rate
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