Urine formation by the kidneys: GFR and RBF
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Transcript of Urine formation by the kidneys: GFR and RBF
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Urine Formation by the Kidneys: Glomerular Filtration, Renal Blood Flow, and Their Control
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Functions of the Kidneys
Excretion of metabolic waste products and foreign chemicals
Regulation of water and electrolyte balances
Regulation of body fluid osmolality and electrolyte concentrations
Regulation of arterial pressure
Regulation of acid-base balance
Secretion, metabolism, and excretion of hormones
Gluconeogenesis
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Physiologic Anatomy of the Kidneys
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The Nephron Is the Functional Unit of
the Kidney
Each human kidney has approximately 1 million nephrons
Each nephron contains a tubule and a glomerulus
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Glomerulus The glomerulus, which is about 200 μm in diameter, is formed by the invagination of a tuft of capillaries into the dilated, blind end of the nephron known as Bowman’s capsule
The capillaries are supplied by an afferent arteriole and drained by the efferent arteriole
The diameter of the afferent arteriole is larger than the efferent arteriole
Glomerular capillary membrane seperates the blood from the glomerular filtrate in Bowman’s capsule
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Glomerular Capillary Membrane
It has three (instead of the usual two) major layers:
the endothelium of the capillary
a basement membrane
a layer of epithelial cells (podocytes)
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The capillary endothelium is perforated by thousands of small holes (70–90 nm in diameter) called fenestrae
Surrounding the endothelium is the basement membrane, which consists of a meshwork of collagen and proteoglycan fibrillae having negative charges
Podocytes surrounds the outer surface of the capillary basement membrane and have numerous pseudopodia that interdigitate to form filtration slits (25nm) along the capillary wall
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Stellate cells called mesangial cells are located between the basal lamina and the endothelium. They are similar to cells called pericytes, which are found in the walls of capillaries elsewhere in the body. The mesangial cells are contractile and play a role in the regulation of glomerular filtration
Functionally, the glomerular membrane permits the free passage of neutral substances up to 4 nm in diameter and almost totally excludes those with diameters greater than 8 nm. However, the charge on molecules as well as their diameters affects their passage into Bowman’s capsule
Albumin (6 nm diameter) is restricted from filtration because of its negative charge and the electrostatic repulsion exerted by negative charges of the glomerular capillary wall proteoglycans
The total area of glomerular capillary endothelium across which filtration occurs in humans is about 0.8 m2
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Section through vascular pole, showing capillary loops
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Relation of mesangial cells and podocytes to glomerular capillaries
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Detail of the way podocytes form filtration slits on the basal lamina, and the relation of the lamina to the
capillary endothelium
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Enlargement of the rectangle in C to show the podocyte processes. The fuzzy material on their surfaces is glomerular
polyanion
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Tubules Fluid filtered from the glomerular capillaries flows into Bowman’s capsule and then into the proximal tubule, which lies in the cortex of the kidney
From the proximal tubule, fluid flows into the loop of Henle, which dips into the renal medulla.
Each loop of Henle consists of a descending and an ascending limb
The walls of the descending limb and the lower end of the ascending limb are very thin and therefore are called the thin segment of the loop of Henle
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After the ascending limb of the loop returns partway back to the cortex, its wall becomes much thicker, and it is referred to as the thick segment of the ascending limb
At the end of the thick ascending limb is a short segment that has in its wall a plaque of specialized epithelial cells, known as the macula densa
The macula, the neighbouring lacis cells , and the renin-secreting granular cells in the afferent arteriole form the juxtaglomerular apparatus
Beyond the macula densa, fluid enters the distal tubule, which lies in the renal cortex. This is followed by the connecting tubule and the cortical collecting tubule, which lead to the cortical collecting duct
The initial parts of 8 to 10 cortical collecting ducts join to form a single larger collecting duct that runs downward into the medulla and becomes the medullary collecting duct
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The epithelium of the collecting ducts is made up of principal cells (P cells) and intercalated cells (I cells)
P cells are involved in Na+ reabsorption and vasopressin-stimulated water reabsorption
I cells are concerned with acid secretion and HCO3– transport
The collecting ducts merge to form progressively larger ducts that eventually empty into the renal pelvis through the tips of the renal papillae
The total length of the nephrons, including the collecting ducts, ranges from 45 to 65 mm
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Cortical nephrons
• 70-80 %
• glomeruli located in the outer cortex
• short loops of Henle that penetrate only a short distance into the medulla
• the entire tubular system is surrounded by an extensive network of peritubular capillaries
Juxtamedullary nephrons
• 20-30 %
• glomeruli lie deep in the renal cortex near the medulla
• long loops of Henle that dip deeply into the medulla, in some cases all the way to the tips of the renal papilla
• Long efferent arterioles extend from the glomeruli down into the outer medulla and then divide into specialized peritubular capillaries called vasa recta
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RENAL CIRCULATION
Peritubular capillaries
Efferent arterioles
Glomerular capillaries
Afferent arterioles
Interlobular arteries
Arcuate arteries
Interlobar arteries
Renal artery
1100 ml/min 20-25% of cardiac output
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JG CELLS
• Myoepitheloid cells• Have golgi apparatus, mitochondria, endoplasmic
reticulum• Secrete renin
Features:a) Baro-receptors: sympathetic stimulationb) Volume receptors : stimulated by hypovoluemia
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MACULA DENSA• Specialized tubular cells• Prominent nuclei• Cells act as chemoreceptor : stimulated by low sodium
concentration• Not innervated
MESENGIAL CELLS• Contacts with JG and macula densa cells• Contractile, regulates GFR
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Urine Formation Results from Glomerular Filtration, Tubular Reabsorption, and Tubular Secretion
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Why are large amounts of solutes filtered and then reabsorbed by the kidneys?
Most waste products are poorly reabsorbed by the tubules and, therefore, depend on a high GFR for effective removal from the body
The entire plasma volume is only about 3 liters, whereas the GFR is about 180 L/day, the entire plasma can be filtered and processed about 60 times each day
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Glomerular Filtration: The First Step in Urine Formation
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Composition of the Glomerular Filtrate
The glomerular capillaries are relatively impermeable to proteins, so the filtered fluid (called the glomerular filtrate) is essentially protein free and devoid of cellular elements, including red blood cells
The concentrations of other constituents of the glomerular filtrate, including most salts and organic molecules, are similar to the concentrations in the plasma
Exceptions to this generalization include a few low molecular-weight substances, such as calcium and fatty acids, that are not freely filtered because they are partially bound to the plasma proteins
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Determinants of the GFR
GFR =Kf × Net filtration pressure
Net filtration pressure = (PG − PB− πG + πB)
Where, Kf is the capillary filtration coefficient (the product of the permeability and surface area of the capillaries),
PG is the glomerular hydrostatic pressure,
PB is the hydrostatic pressure in Bowman’s capsule,
πG is the colloid osmotic pressure of the glomerular capillaries,
πB is the colloid osmotic pressure in Bowman’s capsule
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Summary of forces causing filtration by the glomerular capillaries. The values shown are estimates for healthy humans
Bowman’s capsule oncotic pressure = 0 mm Hg
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Net filtration pressure = 60 + 0 - 18 - 32 = +10 mm Hg
Kf is calculated to be about 12.5 ml/min/mm Hg of filtration pressure
In the average adult human, the GFR is about 125 ml/min, or 180 L/day
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(AP=arterial pressure)
(RE=Efferent arteriolar resistance)
(RA=Afferent arteriolar resistance)
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Blood flow to the two kidneys is normally about 22 percent of the cardiac output, or 1100 ml/min
The renal circulation is unique in having two capillary beds, the glomerular and peritubular capillaries
High hydrostatic pressure in the glomerular capillaries (about 60 mm Hg) causes rapid fluid filtration, whereas a much lower hydrostatic pressure in the peritubular capillaries (about 13 mm Hg) permits rapid fluid reabsorption
Filtration fraction = GFR/Renal plasma flowfiltration fraction, is normally 0.16–0.20
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By adjusting the resistance of the afferent and efferent arterioles, the kidneys can regulate the hydrostatic pressure in both the glomerular and the peritubular capillaries, thereby changing the rate of glomerular filtration, tubular reabsorption, or both in response to body homeostatic demands
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Physiologic Control of Glomerular Filtration and Renal Blood Flow
Strong activation of the renal sympathetic nerves can constrict the renal arterioles and decrease renal blood flow and GFR. Moderate or mild sympathetic stimulation has little influence on renal blood flow and GFR
Several hormones and autacoids can influence GFR and renal blood flow, as summarized in following Table
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Norepinephrine, epinephrine and endothelin constrict afferent and efferent arterioles,causing reductions in GFR and renal blood flow
Afferent arterioles, appear to be relatively protected from angiotensin II–mediated constriction in most physiologic conditions due to release of vasodilators, especially nitric oxide and prostaglandins. The efferent arterioles, however, are highly sensitive to angiotensin II.
Increased angiotensin II formation usually occurs in circumstances associated with decreased arterial pressure or volume depletion, which tend to decrease GFR. In these circumstances, the increased level of angiotensin II, by constricting efferent arterioles, helps prevent decreases in glomerular hydrostatic pressure and GFR
prostaglandins (PGE2 and PGI2), bradykinin, and endothelial-derived nitric oxide cause vasodilation and increased renal blood flow and GFR
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Autoregulation of GFR and Renal Blood Flow
The kidneys have effective mechanisms for maintaining renal blood flow and GFR relatively constant over an arterial pressure range between 80 and 170 mm Hg, a process called autoregulation
MECHANISMS
Tubuloglomerular feedback Myogenic autoregulation of renal blood flow
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Tubuloglomerular Feedback and Autoregulation of GFR
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Myogenic Autoregulation of Renal Blood Flow and GFR
The myogenic hypothesis states that increased arterial pressure stretches the blood vessels, which causes reflex contraction of smooth muscle in the blood vessel walls and consequently increased resistance to blood flow
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ANGIOTENSIN II• Alpha globulin, synthesized in liver• ACE : in lung epithelium• Actions: 1. Most potent vasoconstrictor2. Aldosterone secretion 3. Contraction of mesangial cells : GFR4. Direct action on renal tubular cells : increased
sodium reabsorbtion5. Increase water intake
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ERYTHROPOIETIN• Glycoprotein• Acts on stem cells of bone marrow • Secreted from interstitial cells of peritubular
capillaries 85% and perivenous hepatocytes of liver 15%
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Q1. Function/s of kidney is/are:
a) Glycogenolysisb) Secretion of thrombopoietinc) Acid-base balanced) Both (b) and (c)
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Q2. Average number of nephrons in both kidneys are:
a) 1 millionb) 2 millionc) 4 milliond) none
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Q3. Glomerular capillary membrane is formed of:
a) Endothelium of the capillaryb) Basement membrane of the capillaryc) Podocytesd) All of the above
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Q4. True about juxtamedullary nephrons is:
a) 70-80%b) Short loop of Henlec) Vasa rectad) All of the above
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Q5. Albumin is not filtered because of:
a) Large size/diameterb) Negative charge on basement membranec) Both (a) and (b)d) None
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Q6. Juxtaglomerular apparatus is formed of:
a) Lacis cellsb) Juxtaglomerular cellsc) Macula densad) All of the above
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Q7. Erythropoietin is secreted by:
a) Juxtaglomerular cellsb) Interstitial cells around peritubular capillariesc) Macula densad) Lacis cells
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Q8. Renin is secreted by:
a) Juxtaglomerular cellsb) Interstitial cells around peritubular capillariesc) Macula densad) Lacis cells
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Q9. GFR depends on :
a) glomerular hydrostatic pressureb) glomerular colloid osmotic pressurec) hydrostatic pressure in Bowman’s capsuled) All of the above
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Q10. net filtration pressure in glomerulus is about:
a) 10 mm Hgb) 18 mm Hgc) 32 mm Hgd) 60 mm Hg
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Q11. true about filtration fraction :
a) Filtration fraction = GFR/Renal plasma flowb) Filtration fraction = Renal plasma flow/GFRc) is more than 0.25d) Both (a) and (b)
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Q12. isolated constriction of efferent arteriole :
a) Increases renal plasma flowb) Decreases GFRc) No change in filtration fractiond) None of the above
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Q13. renal blood flow and GFR remains relatively constant over an arterial pressure range of :
a) 40 – 130 mm Hgb) 60 – 150 mm H gc) 80 – 170 mm Hgd) None of the above
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Q14. during decreased arterial pressure, tubuloglomerular feedback in nephrons will cause:
a) Increased renin secretionb) Decreased efferent arteriolar resistancec) Increased afferent arteriolar resistanced) All of the above