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Renal Physiology 1
25% of the blood pumps to the renal organs, making it…
Renal Physiology 1
- 25% of the blood pumps to the renal organs, making it a rather important organ
Overview of the various components and functions in the urinary (renal) system.
- 66% of water, and Nacl absorbed
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Identify the basic functions performed by nephrons, and understand the concepts of glomerular filtration, tubular reabsorption, tubular secretion and excretion
3 Basic Renal Processes for the Formation of Urine
- Glomerular filtration
- Tubular reabsorption
- Tubular secretion
Highly efficient process, only 20% of the plasma that passes through the glomerulus is filtered, with <1% of filtered fluid is excreted.
Glomerular filtration
- First step of urine production
- Water and most solutes (minus proteins, which are too big to pass through the filter) in blood plasma move across the wall of glomerular capillaries
- They are then filtered and move into the glomerular capsule and then into the renal tubule
- Highly efficient process.
Glomerular Capsule
- Outer wall is lined by simple squamous capsular epithelium. Continuous with visceral epithelium that covers glomerular capillaries, separated by capsular space.
- Visceral Epithelium - consists of large cells (podocytes), with complex processes or “feet” that wrap around specialized dense layer of glomerular capillaries.
- Filtration Slits - are narrow gaps between adjacent pedicels. Materials passing out of blood at glomerulus must be small enough to pass between filtration slits
Water and Solutes (minus proteins) pass from plasma to capsular space
- 1st layer of capillary: Fenestration (pore) of glomerular endothelial cells prevents filtration of blood cells, but allow components of blood plasma to pass through
- 2nd layer: Basal lamina membrane prevents filtration of large proteins
- 3rd layer: Silt membrane prevents filtration of medium proteins
What drives filtration?
- Glomerular blood hydrostatic pressure (55 mmHg) is the major force that induces glomerular filtration.
- Bowman’s Capsular hydrostatic pressure (CHP,15 mmHg) is the hydrostatic pressure exerted against the filtration membrane by fluid already in the capsular space and renal tubule. CHP opposes filtration and represents a “back pressure”.
- Blood colloid osmotic pressure (30 mmHg), colloid osmotic pressure gradient due to proteins in plasma but not in Bowman’s capsule.
Glomerular blood hydrostatic pressure promotes filtration, whereas capsular hydrostatic pressure and blood colloid osmotic pressure oppose filtration.
- Glomerula blood hydrostatic pressure is 55mmHg
- Capsular Hydropstatic pressure is 15mmHg
- Blood colloid osomotic pressure is 30mmHg
Net filtration pressure is 55-15-30=10mmHg that goes into the PCT. So with this, higher GBHP will promote filtration
Glomerular Filtration Rate
- 2 Factors
- Net filtration pressure
- Filtration coefficient
- Surface area of glomerular capillaries available for filtration
- Permeability of interface between capillary and Bowman's Capsule
GFR
- Control via 3 ways:
- Autoregulation
- Autonomic regulation
- Hormonal
Autoregulation
- Maintains GFR despite changes in local blood pressure and blood flow by changing diameters of afferent arterioles, efferent arterioles, and glomerular capillaries, known as myogenic response.
- Reduced blood flow or glomerular blood pressure triggers:
- Dilation of afferent arteriole
- Dilation of glomerular capillaries
- Constriction of efferent arterioles.
- Rise in renal blood pressure
- Stretches walls of afferent arterioles
- Causes smooth muscle cells to contract, constricts afferent arterioles
- Decreases glomerular blood flow.
- Constant GFR when mean arterial pressure is between 80 and 180mmHg (see graph)
Juxtaglomerular Apparatus
- The tubuloglomerular feedback mechanism involves the specialized combination of tubular and vascular cells of the juxtaglomerular apparatus (DCT).
- The macula densa cells detect changes in salt level of the fluid flowing past.
- Increased salt in the fluid causes the macula densa to secrete ATP and adenosine.
- These paracrine molecules cause the smooth muscles of the adjacent afferent arteriole to constrict, reducing blood flow into the glomerulus and reducing GFR.
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Hormonal Regulation
Two hormones: Renin–angiotensin-aldosterone system (RAAS) & Atrial
Natriuretic peptide (ANP).
The Renin–Angiotensin-Aldosterone System
- Three stimuli cause the juxtaglomerular complex (JGC) to release renin:
- Decline in blood pressure at glomerulus due to decrease in blood volume, fall in systemic pressures.
- Stimulation of juxtaglomerular cells by sympathetic innervation.
- Decline in osmotic concentration of tubular fluid at macula densa.
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Angiotensin II Activation
- Constricts efferent arterioles of nephron, elevating glomerular pressures and filtration rates
- Stimulates reabsorption of Na+ ions and water at PCT.
- Stimulates secretion of aldosterone by adrenal cortex in the DCT and collecting tubules
- Increase Na+, Cl-, water reabsorption, loss K+.
- Stimulates thirst.
- Triggers release of antidiuretic hormone (ADH)/Vasopressin, stimulates reabsorption of water in DCT and collecting tubules.
- Angiotensin II constricts glomerular arterioles, having a greater effect on efferent arterioles than afferent.
- As with most other capillary beds in the body, the constriction of afferent arterioles increases the arteriolar resistance, raising systemic arterial blood pressure.
Net Filtration Pressure
- Vasoconstriction (reduce blood flow)> Glomerular capillary blood pressure decreases > net filtration pressure decreases > GFR decreases
- Vasodilation > GFT increases
Autonomic regulation
- The sympathetic nervous system, via the release of norepinephrine, can cause constriction of the afferent arteriole, which leads to a decrease in renal blood flow and, consequently, a decrease in GFR.
- The parasympathetic nervous system, via the release of acetylcholine, can cause dilation of the afferent arteriole, which leads to an increase in renal blood flow and, consequently, an increase in GFR.
Tubular Reabsorption at glomerular capillaries
- All plasma constituents except plasma proteins are indiscriminately filtered through the glomerular capillaries.
- This includes wastes (ie, urea) and desirable materials such as nutrients (ie, glucose, amino acids), electrolytes (ie, Na+, Cl-, HCO3 -) and other substances too important to lose in the urine.
- These essential materials are brought back into the plasma by tubular reabsorption.
Tubular reabsorption is highly efficient, selective, and variable.
PCT
- Trans-cellular transport
- Substances cross the luminal and baso-lateral membranes of the tubule epithelial cells.
- Para-cellular pathway
- Substances pass through inter-cellular junctions
- ~66% of water and sodium chloride are reabsorbed here
- Almost all the K+ reabsorbed
Glucose
- Via primary, secondary transports for reabsorption
- Only reabsorbed at the PCT, nowhere else 100%
Sodium uses the SGLT, Sodium-Glucose Linked Transporter, to pull glucose into the cell against its concentration gradient (symport)
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Transport Maximum
- Filtration of glucose is proportional to plasma concentration. No saturation
- Reabsorption of glucose is proportional to plasma concentration, until Transport Maximum is reached Typically 300mg/100mL
- Excretion = Filtration - Reabsorption
- If renal threshold of 300mg/100mL is breached, perhaps not enough insulin, then glucose is excreted in urine, meaning diabetes
Summary of Activities at PCT
- Microvilli increases surface area
- Glucose, sodium and water transported to peritubular capillary here
- Regulates blood PH level because HCO3- transported to peritubular capillary
- Extracts H+ and into the tubular from capillaries, hence urine is slightly acidic.
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Tubular Secretion and Reabsorption by DCT
- Angiotensin II stimulates the release aldosterone, a hormone that in turn stimulates the principal cells in the collecting ducts to reabsorb more Na+ and Cl- and secrete more K+.
- The osmotic consequence of reabsorbing more Na+ and Cl- is that more water is reabsorbed, which causes an increase in blood volume and blood pressure.
Pumps at DCT are stimulated by aldosterone
- More K+ is secreted into the lumen of the DCT, and hence urinated out
Mechanism of action of Antidiuretic hormone (ADH)/Vasopressin
- Binds with V2 receptors in the basolateral membrane of the principal tubular cells lining the distal and collecting tubules. This binding results in the insertion of aquaporins into the luminal membrane and promote reabsorption of water in the distal segments of the nephron.
Illustrate the process
- 1 more item...
Peritubular Capillaries
- Lower hydrostatic pressure in peritubular capillaries results in net absorption of interstitial fluid (solutes and water).
- Colloid pressure (30 mmHg) favours movement of fluid into the capillaries as the average hydrostatic pressure at 10 mmHg.
- 20 mmHg pressure gradient leads to movement of fluid into the capillaries.
Tubular reabsorption
- As filtered fluid flows through the renal tubules and through the collecting ducts
- Tubule cells reabsorb about 99% of the filtered water and many useful solutes.
- The water and solutes return to the blood as it flows through the peritubular capillaries and vasa recta.
Transepithelial transport
The reabsorbed substance must pass through five layers
- Luminal/apical membrane of the tubular cell
- Cytosol of the tubular cell
- Basolateral membrane of the tubular cell
- Interstitial fluid
- Capillary wall, to enter blood plasma.
- Can be either passive (diffusion) or active (i.e. Na+K+ pump).
Na+ Reabsorption
- The basolateral Na+-K+ pump actively transports Na+ from the tubular cell into the interstitial fluid.
- This process establishes a concentration gradient for passive movement of Na+ from
- Lumen into the tubular cell
- Lateral space into the peritubular capillary.
This accomplishes net transport of Na+ from the tubular lumen into the blood at the expense of energy
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Tubular secretion
- As filtered fluid flows through the renal tubules and collecting ducts
- The renal tubule and duct cells secrete other materials, such as wastes, drugs, and excess ions, into the fluid.
- Notice that tubular secretion removes a substance from the blood.
- Transfer of molecules from extracellular fluid into lumen of the nephron.
- Active process: important in homeostatic regulation, ie, K+ and H+ via their gates or pumps
- Secretes drugs & environmental toxins, ie, Penicillin
Amount of solute excreted is how much filtered, minus amount absorbed and add amount secreted.
100% = 20% filtered
Describe how specific segments of the renal tubule and collecting duct reabsorb water and solutes and secretes solutes into urine.
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Increase plasma K+
Plasma Regulation
- K+ balance is maintained by excreting the amount ingested minus the amount lost in feces, sweat and urine.
- Hyperkalemia: High plasma K+
- Causes cardiac arrhythmias and increased excitability of neurons and skeletal muscles. Polarisation issues.
- Correction: increased aldosterone release and secretion of K+
- Hypokalemia: Low plasma K+.
- Result of kidney disease, diarrhea and diuretics.
- Causes muscle weakness and failure of respiratory muscles and the heart.
- Correction: no secretion of K+ into the collecting ducts
Kidneys play a key role in K+ regulation
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FYI: The different types of cells allow the nephron to perform different functions
- Microvilli allows sodium and
- Squamous cells allow water to be reabsorbed
- Cuboidal cells regulate sodium and potassium via the gates
- Principal cells at collecting duct regulate sodium, chloride, potassium and water.
- Intercalated cells regulate pH
- Slightly acidic urine keeps the bacteria in check
Read up in Martini
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If there is enough SGLTs, then normal function. If more glucose than SGLTs, threshold breached (300mg/100mL), or the transport maximum, glucose will get excreted
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Proceeds to Loop of Henle, then
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