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What are kidney functions?
Removal of toxins, metabolic wastes, and excess ions from the blood, Regulation of blood volume, chemical composition, pH, Gluconeogenesis during prolonged fasting, Endocrine functions, and Activation of vitamin D
How do the kidneys regulate blood volume?
Determines how much filtrate it needs to put back in blood to equalize blood volume
How do the kidneys regulate chemical composition?
It determines what electrolytes to take up and how much to put back
How do the kidneys regulate pH?
By determining how much hydrogen needs to be taken up or put back to keep the bloods pH between 7.35-7.45
How do the kidneys regulate endocrine function?
by releasing Renin (regulation of blood pressure and kidney function) and Erythropoietin
Where in the body are the kidneys located?
Retroperitoneal, in the superior lumbar region; the right kidney is lower than the left
Ureters, renal blood vessels, lymphatics, and nerves enter and exit where?
At the hilum of the kidney
What are the minor calyces of the kidney?
The branching channels of the renal pelvis that filter into the major calyces
What are the major calyces of the kidneys?
The branching channels of the renal pelvis that collects urine from minor calyces, and empties urine into the pelvis
How does urine flow from the collecting ducts?
Collecting duct → renal papillae →renal pyramids → minor calyces → major calyces → renal pelvis → ureters → bladder → urethra
How much blood flows into the kidneys via the renal artery each minute?
¼ of cardiac output or 1200 mL
State the sequence of blood flow through the kidney starting from the aorta?
Aorta → renal artery → segmental artery → interlobar artery → arcuate artery → cortical radiate artery →[afferent arteriole →glomerulus (capillaries) →efferent arteriole → peritubular capillaries and vasa recta](glomerulus blood filtration) → cortical radiate vein →arcuate vein → interlobar vein → renal vein → inferior vena cava
What is the purpose of having glomerulus composed of fenestrated glomerular endothelium?
Allows filtrate to pass from plasma into the glomerular capsule (Bowman's capsule)
What is a renal tubule?
Part of a nephron, that begins as a cup-shaped glomerular capsule (Bowman's capsule) surrounding the glomerulus and continues as the proximal convoluted tubule (PCT) and loop of henle, and finally distal convoluted tubule (DCT). This is where what is filtered out of the blood gets a chance to go back to blood or remain in tubules to turn into urine.
What is a proximal convoluted tubule (PCT)?
The tubule that is closest to the glomerulus; and composed of cuboidal cells with dense microvilli and large mitochondria. It is confined to the renal cortex.
What are the characteristics of the descending limb of the loop of henle?
It is composed of thin walls and is freely permeable to water but not solutes
What are the characteristics of the ascending limb of the loop of henle?
It is composed of a thick wall and is freely permeable to solutes but not water
What is the distal convoluted tubule (DCT)?
The tubule furthest from the glomerulus confined to the cortex.
What are collecting ducts?
A receiving chamber for many nephrons; that deliver urine from the nephrons through the papillae to be passed through the kidney and excreted.
What are cortical nephrons?
Nephrons that almost entirely remain in the renal cortex therefore the reabsorption is occurring in the peritubular capillaries. Makes up the majority of nephrons (85%)
What are juxtamedullary nephrons?
Nephrons that consist of a long Loop of Henle that deeply invades the renal medulla; therefore reabsorption is occurring in the vasa recta
What are peritubular capillaries?
Capillaries that arise from efferent arteriole in cortical nephrons that cling to adjacent tubules
What are vasa recta?
Vessels that arise from efferent arterioles of juxtamedullary nephrons that are parallel to the long loops of henle.
Explain the how the blood flow and filtration in the glomerulus is possible.
The blood enters the glomerulus via afferent arteriole and exits at the efferent arterioles. The movement is essential in creating backpressure in the glomerulus due to the size of the afferent (smaller) and efferent arterioles. The afferent arteriole gives rise to the glomerular capillaries where the high pressure forces the plasma (minus proteins) into the Bowman's capsule for filtration. The RBC's and protein continue out the efferent arterioles into the peritubular capillaries where many "lanes" open up reducing pressure.
What is the juxtaglomerular Apparatus?
The area where the cells of the DCT that touch the back of the glomerulus. Regulatory cells that controls flow rate of blood through the glomerular capillaries hence the rate of filtration. One per nephron.
How does the juxtaglomerular apparatus work?
Via granular cells in the afferent arteriole, macula densa cells in the DCT and extraglomerular mesangial cells.
What are granular cells?
Granular cells (juxtaglomerular/JG cells) in the arteriole changes vessel diameter by produce renin to by sensing the blood pressure in the kidneys
What are macula densa cells?
Macula densa cells in the DCT sense changes in sodium chloride content in filtrate, in order to adjust filtration rate.
What are extraglomerular mesangial cells?
Extraglomerular mesangial cells are communicator cells for the granular and macula densa cells.
There is a lot of resistance in the afferent and efferent arterioles which cause blood pressure to do what?
Decline from 95 mm Hg to 8 mm Hg in the kidneys.
Why do we want the resistance in afferent arterioles?
Afferent: We don't want to blow out the capillaries in the glomerulus.
Why do we want the resistance in efferent arterioles?
Maintains high glomerular pressure, and reduces hydrostatic pressure in peritubular capillaries
What would happen to the glomerular capillaries if a person has chronic high blood pressure and what might be a sign of this?
Capillaries would burst, blood might be seen in the urine (blood in urine can mean many other things)
What is the filtration membrane?
The porous membrane between the blood and the capsular space that allows the passage of water and solutes smaller than most plasma membranes
What does the filtration membrane consist of?
Fenestrated endothelium of the glomerular capillaries, podocytes with foot processes and filtration slits), and gel-like basement membrane
How does the filtration membrane keep proteins and RBC from passing through?
Fenestrations prevent filtration of blood cells, basement membrane is negatively charged so it repels the proteins (large anions), and slit diaphragms also help to repel macromolecules
What are glomerular mesangial cells?
Cells in the filtration membrane that engulf and degrade macromolecules, they can also contract to change the total surface area available for filtration.
What is urine?
Composed of less than 1% of total filtrate; contains metabolic wastes and unneeded substances.
What are the mechanisms of urine formation?
Glomerular filtration, tubular reabsorption, and tubular secretion
What is glomerular filtration?
A passive mechanical process driven by hydrostatic pressure that separates filtrate from blood, non-specifically. The molecules that are not filtered and move to efferent arteriole and maintains colloid osmotic pressure of the blood
What is net filtration pressure (NFP)?
The pressure responsible for filtrate formation, it is simply the difference between the pressure in the capillaries in the glomerulus and the pressure in the filtrate. (10 mm Hg)
What is the glomerular hydrostatic pressure (HPg)?
Pressure against inside of capillary walls (55 mm Hg)
What is the colloid osmotic pressure (Opg)?
Pressure put on filtrate water to want to go in and dilute out proteins due to intracellular proteins and electrolytes (30 mm Hg)
What is capsular hydrostatic pressure (HPc)?
Pressure exerted by filtrate on capillary wall that puts water back into capillaries (15 mm Hg)
What is glomerular filtration rate (GFR)?
Volume of filtrate formed per minute by the kidneys (120-125 mL/min)
What is glomerular filtration rate governed by (GFR)?
Total surface area available for filtration, filtration membrane permeability, and net filtration pressure
What are the intrinsic controls controlling glomerular filtration?
Renal autoregulation; act locally with the kidney. Regulated by smooth muscle in response to stretch. Has to do with myogenic mechanisms and tubuloglomerular feedback mechanism.
What would you expect to see in GFR as a result of myogenic mechanism?
If you increase the diameter of the afferent arteriole - more blood flows into glomerular capillaries increasing hydrostatic pressure therefore increasing GFR (b/c less time for reabsorption). If you decrease the arteriole diameter - less blood would flows into glomerular capillaries which decreases hydrostatic pressure and therefore decrease GFR (b/c more time for reabsorption).
What would you expect to see in GFR as a result of the tubuloglomerular feedback mechanism?
Juxtaglomerular apparatus looks at systemic blood pressure and sodium chloride levels and decides how to regulate glomerular filtration.
If the sodium chloride is high in filtrate and the GFR is high, the tubules don't have enough time to absorb it, so the juxtamedullary apparatus slows filtration. How does this happen?
Macula densa cells of the JGA respond to high sodium chloride by releasing a vasoconstricting chemical that acts on the afferent arteriole constricts the blood coming in and slows down flow rate allowing for more time for absorption.
If blood pressure was to increase what would you expect to see as a result of myogenic mechanism?
Constriction of afferent arterioles to help maintain glomerular filtration rate and protect glomeruli from damaging high BP
If blood pressure was to decrease what would you expect to see as a result of myogenic mechanism?
Dilation of afferent arterioles helps maintain glomerular filtration rate
What extrinsic controls are in charge under normal conditions at rest?
Renal blood vessels are dilated and renal autoregulation mechanisms prevail
What extrinsic controls are in charge when under extreme stress?
Norepinephrine and epinephrine are released, causing vasoconstriction (which reduces urinary output) and triggers the release of renin (which triggers the renin-angiotensin mechanism)
What is the renin-angiotensin mechanism?
Renin to angiotensinogen to angiotensin I which is catalyzed by ACE into angiotensin II
What are the effects of angiotensin II?
Triggers the release ofaldosterone, and ADH . Activates the thirst center, Constricts efferent arterioles, increases fluid reabsorption, and causes glomerular mesangial cells to contract, decreasing the surface area available for filtration
What are the other factors affecting GFR?
Prostaglandin E2, Intrarenal angiotensin II, and adenosine
How does prostaglandin E2 affect GFR?
Vasodilator that counteracts vasoconstriction by norepinephrine and angiotensin II. It prevents renal damage when peripheral resistance is increased
What is tubular reabsorption?
The return of almost all of the filtrate (99%) to the peritubular capillaries by a selective transepithelial process, and hormonal regulation. Includes active and passive process.
What is the transcellular route in tubular reabsorption?
Transport takes place through the cell plasma membranes. Can transport through luminal membranes, diffuses through the cytosol, and across the basolateral membrane of tubule cells, into the interstitial fluid and into the peritubular capillary
What is the paracellular route in tubular reabsorption?
Transport takes place between cells and is limited to water movement and reabsorption of calcium, magnesium, phosphate, and some sodium in the PCT where tight junctions are leaky.
What if a substance cannot travel via transcellular or paracellular?
By transport proteins in the plasma membrane of the luminal wall that are going to actively transport them into the cell and then sometimes when they get in the cell the mechanism is diffusion and sometimes there are transport mechanisms that will take them further.4
Sodium is the most abundant active cation in the filtrate. How is it reabsorbed?
Primary active transport out of the tubule cell by the sodium-potassium ATPase pump. Secondary active transport or facilitated diffusion mechanisms through the luminal membrane. Meaning that once these cells expend some energy (Active transport) getting sodium from the filtrate through the wall of the tubule into the interstitial fluid and on in to the capillary you have created an ion gradient. By means of water and other solutes, water usually carries lots of solutes with it including sodium, waters going to follow salt and bring a lot of electrolytes with it (Passive transport).
What kind of pressure do you want to aid in reabsorption of sodium?
You want low hydrostatic pressure and high osmotic pressure in the peritubular capillaries to promote bulk flow of water and solutes.
What is the function of the PCT?
Site of most reabsorption. Reabsorbs 65% of sodium and water, all nutrients, ions, and small proteins.
What is reabsorbed in the descending loop of henle?
Water is reabsorbed from the tubule into the peritubular capillaries
What is the body reabsorbing in the ascending loop of henle?
Sodium, potassium, and chloride is reabsorbed from the tubule into the peritubular capillaries
What is reabsorbed in the DCT and collecting ducts?
All reabsorption is hormonally regulated. Calcium is absorbed by the hormone PTH, water is reabsorbed by the hormone ADH, and sodium is reabsorbed by the hormone aldosterone and ANP.
Where is aldosterone secreted?
Aldosterone is secreted by the granular cells in the juxtaglomerular apparatus in response to low sodium content or low blood pressure. If both of these exist you take in sodium and water follows transports more water into blood stream to increase blood pressure and sodium will follow increasing sodium content.
What are tubular secretions?
Reverse of reabsorption: selective addition to urine (capillaries to urine). At the end of the renal tubules sensory cells determine if there is an imbalance of potassium, hydrogen, ammonia, creatinine, and organic acids and fix it by putting it back in the urine. Also plasma proteins that are transporting things around in the blood and they need to get rid of it will secrete it back into filtrate. Eliminates undesirable substances that have been passively reabsorbed. Rids the body of excess potassium, and controls blood pH by altering amount of hydrogen or bicarbonate in the urine
How is Urine concentration and volume regulated?
Sensory cells in the JGA look at osmolality. High salt concentration in filtrate will cause the afferent arteriole to dilate increasing volume. The opposite for low concentration.
How does the countercurrent mechanism works and what it is useful for?
The countercurrent mechanism, in the loop of henle, establishes the osmotic gradient is to allow the nephron to form more concentrated urine by allowing for maximal water reabsorbing. The Descending loop is only permeable to water, therefore as move water leaves the filtrate causing sodium concentration to increase (increased osmalarity). The ascending loop is only permeable to NaCl, which wants to leave its area of high concentration and go into the interstitial space which because of the descending loop has higher water content. The result is decreased solute concentration (decrease in osmalarity) in the ascending limb. When the water moves into the space surrounding the nephron, this attracts the NaCl from the ascending limb into that space. And when the NaCl from the ascending limb moves into the space it encourages water from the descending limb to follow, therefore they work together to create this gradient.
Where is diluted filtrate travel in the absence of ADH?
In the absence of ADH, dilute filtrate continues into the renal pelvis as dilute urine, but you realize if ADH is present ADH is going to stimulate the uptake of sodium and water follows.
How is concentrated urine formed?
Depends on the medullary osmotic gradient and ADH; which triggers reabsorption of water in the collecting ducts
What is facultative water reabsorption?
Water reabsorption that depends on the presence of ADH 99% of water in filtrate is reabsorbed
What is renal clearance tests used for?
Determine GFR, Detect glomerular damage, or follow the progress of renal diseases.
How would you calculate renal clearance?
RC (renal clearance rate- mL/min) = U (concentration of the substance in urine mg/mL) x V (flow rate of urine formation- ml/min) all divided by P (concentration of the same substance in plasma. RC = (U x V)/P
What is the anatomical position of the ureters?
Retroperitoneal; they enter the base of the bladder through the posterior wall
How do the ureters prevent backflow?
As bladder pressure increases, distal ends of the ureters close
What are the three walls of the ureter?
Lining of transitional epithelium, smooth muscle muscularis (contracts in response to stretch), and outer adventitia of fibrous connective tissue.
What can occur when there are large kidney stones present?
Block ureter, cause pressure and pain in kidneys
What are factors that can cause Kidney stones?
Chronic bacterial infection, urine retention, ↑calcium in blood, or ↑pH of urine
What is the function of the urinary bladder?
Urinary bladder is a muscular sac for temporary storage reservoir for urine
What is the anatomical position of the bladder?
Retroperitoneal, on pelvic floor, posterior to pubic symphysis: On males the prostate gland surrounds the neck inferiorly, and on females it is anterior to the vagina and uterus
What is the trigone?
Smooth triangular area outlined by the openings for the ureters and the urethra. This area is where infections tend to persist.
What are the 3 layers of the bladder wall?
Transitional epithelial mucosa, thick detrusor (3 layers of smooth muscle), and fibrous adventitia (peritoneum on superior surface only)
In what direction and when does the urinary bladder expand?
Expands and rises superiorly during filling without a significant rise in internal pressure
What is the function of the urethra?
Urethra is a muscular tube that transports urine out of the body
What is the lining of the urethra?
Mostly psuedostratified columnar epithelium, except transitional epithelia near bladder, and stratified squamous epithelia near external urethral orifice
What is the internal urethra sphincter?
Involuntary smooth muscle at bladder-urethra junction that contracts to open
What is the external urethra sphincter?
Voluntary skeletal muscle surrounding the urethra as it passes through the pelvic floor
Describe the female urethra.
3-4 cm in length tightly bound to the anterior vaginal wall. External urethra orifice is anterior to the vaginal opening, posterior to the clitoris
Describe the male urethra.
Carries both semen and urine and is composed of three regions the prostatic urethra, the membranous urethra, and the spongy urethra
Describe the spongy urethra.
15 cm in length passes through the penis and opens via the external urethral orifice
What are the three simultaneous events of micturition?
Contraction of detrusor muscle, opening of internal urethra sphincter (both by ANS), and opening of external urethral sphincter by somatic nervous system
How does reflexive urination occur?
Distention of bladder activates stretch receptors, excitation of parasympathetic neurons in reflex center in sacral region of spinal cord, contraction of the detrusor muscle, contraction (opening) of the internal sphincter, and inhibition of somatic pathways to external sphincter, allowing its relaxation (opening)
What is the concentration of hydrogen ions regulated by (in sequential order)?
Chemical buffer system, respiratory system, and urinary system.
What is the chemical buffer system?
The chemical buffer system of one or more compounds that act to resist pH changes when strong acid or base is added.
What are the 3 different chemical buffers?
Bicarbonate buffering system, phosphate buffering system, and protein buffering system
What is the bicarbonate buffer system?
Known as the workhorse of the buffer systems, it's the main buffer in the extracellular fluid even though it buffers both. It's a mixture of carbonic acid and its salt, for example if the salt was sodium then the bicarbonate buffer would be sodium bicarbonate (NaHCO3).
How would the bicarbonate buffer system react to a strong acid?
If a strong acid, such as HCl is added: HCl + NaHCO3 → H2CO3 + NaCl So if bicarbonate ions find themselves in acidic solutions, they tend to act like the weak base they can be, and suck up the excess hydrogen ions lowering the pH (Keep in mind that this is just a disguise mechanism because the pH would only be lowered slightly).
What happens to the bicarbonate buffer if a strong base is added?
If it is in a strong basic such as sodium hydroxide (NaOH) is added to a strong basic solution like sodium bicarbonate (NaHCO3), there are very few free floating hydrogen ions. In this condition, the bicarbonate reaction cannot proceed to the left, since no hydrogen ion is available. Instead it will go to the right, so that free floating hydrogen (H(+)) can tie up to OH(-) released by the strong base. NaOH + H¬2CO3 → NaHCO3¬ + H2O. In this manner, bicarbonate ions will tend to act like the weak acid they can be, and release hydrogen ions.
What is unique about the H2CO3 supply?
It is almost limitless and is subject to respiratory controls (from CO2 released by respirations)
What is the phosphate buffering system?
Nearly identical to the bicarbonate buffer system. The components are sodium salts of dihydrogen phosphate(H2PO4(-) so it's NaH2PO4(-) (a weak acid) and the monohydrogen phosphate (HPO4(2-)) so it's NaH2PO4(2-) a weak base. Effective buffer in urine and ICF, where phosphate concentrations are high.
What happens to the phosphate buffer if a strong acid is added?
Like the bicarbonate buffer if a strong acid such as HCl is added it is tied up in weak acids: HCl + Na2HPO4 → NaH2PO4 +NaCl (pH is slightly lowered)
What happens to the phosphate buffer if a strong base is added?
Like the bicarbonate buffer if a strong base is added they are converted to weak bases: NaOH + NaH2PO4 → Na2HPO4 + H2O (pH is slightly elevated)
What is the protein buffer system?
The main buffer system inside of cells (because lots of proteins are inside the cells). Protein molecules are amphoteric (can function as both weak acid and a weak base) so when pH rises, organic acid or carboxyl (COOH) groups release hydrogen, or when pH falls, NH2 groups bind hydrogen.
What are the physiological buffer systems?
The respiratory and renal system. They act more slowly than chemical buffers systems, and have more capacity than chemical buffer systems. Only the respiratory and urinary systems eliminate excess acids or bases from the body.
How does the respiratory buffer regulate pH?
It's not as fast as the chemical buffer system takes 1-3 min to act. The respiratory system eliminates CO2 by exhaling carbon dioxide and water. This signals the hydrogen ions (H(+)) to combine to the bicarbonate (HCO3) to form carbonic acid (H2CO3); which dissociates into your needed carbon dioxide (CO2) and water (H2O) ; because of you now have less hydrogen (H(+)) that forces the non-bicarbonate buffer system to release more hydrogen ion (H(+)) which is fed back into the system.
How does the respiratory buffer system react to an increase in acidity (↑H)?
The lungs step in to compensate by hyperventilating causing a decrease in carbon dioxide (CO2) which will cause a decrease in hydrogen ions (H(+)).
How does the respiratory buffer system react to alkalosis(↓H)?
The lungs will compensate by hypoventilating in order to increase carbon dioxide (CO2) which will cause an increase in hydrogen (H(+)).
What happens in the respiratory buffer during CO2 unloading?
The reaction shifts towards the deficit so to the left CO2 + H20 ← H2CO3 ← H(+) +HCO3(-).
What happens in the respiratory buffer during CO2 loading?
The reaction shifts toward the deficit so to the right CO2 + H20 →H2CO3 → H(+) +HCO3(-).
What would happen in respiratory regulation if there was too much CO2 or hypercapnia?
Medullary chemoreceptors would be stimulated that respond by increasing respiratory rate and depth
How does the renal mechanism regulate pH?
In the filtrate the hydrogen (H+) will combine with the bicarbonate in the blood to form carbonic acid (H2CO3) which will dissociate into water (H2O) and carbon dioxide (CO2). The carbon dioxide (CO2) diffuses into the tubule cell where depending on the pH it can either combine with water (H2O) (under acidic conditions) to form carbonic acid (H2CO3) which dissociates to produce bicarbonate (HCO3) and a hydrogen (H) The hydrogen gets secreted back into the filtrate and the bicarbonate (HCO3) can be reabsorbed into the capillary (in exchange for Na¬+ or Cl-) to buffer the H+ within the blood.
What are the most important renal mechanisms of acid-base balance?
Reabsorbing HCO3, generating new HCO3 and excreting HCO3
Hydrogen (H(+)) secretion occurs in the PCT and in collecting ducts via what cell?
Type A intercalated cells
Where does the secreted hydrogen (H(+)) come from?
H2CO3 produced in reactions catalyzed by carbonic anhydrase inside the cells
What makes the process of replenishing bicarbonate (HCO3) in the filtrate so complex?
The fact that the tubule cells are almost completely impermeable to the HCO3¬ in the filtrate means that they cannot reabsorb them.
How do the kidneys conserve filtered HCO3?
The H2CO3 in the tubule cell dissociates into H+ and HCO3. - H+ is secreted into filtrate, and HCO3 is transported into the interstitial fluid to be taken back into the peritubular capillary.
At what rate does HCO3¬ leave the filtrate?
At the same rate that it enters the peritubular capillary blood.
Where does newly generated HCO3 go?
Moves into interstitial space via a co-transport system and then moves passively into peritubular capillary blood
Where does the HCO3 move to during ammonium excretion and what is excreted as a result?
Moves into the blood and NH4 is excreted in urine
When the body is in alkalosis, type B intercalated cells do what?
Secrete bicarbonate (HCO3(-) and reclaim hydrogen (H(+)) and acidify the body
What is unique about the mechanism of bicarbonate ion secretion?
Mechanism is the opposite of the bicarbonate ion reabsorption process by type A intercalated calls
What is the most important indicator of adequacy of respiratory function?
PCO2 level (normally 35-45)
What are the major causes of metabolic acidosis?
The ingestion of too much alcohol, Excessive loss of HCO3¬, and accumulation of lactic acid.
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