Renal Physiology: Functions and Anatomy

• Study notes for renal physiology

Functions of the Kidney

• Kidneys regulate extracellular fluid volume and blood pressure by removing excess fluid to lower blood pressure and conserving blood during low blood pressure, resulting in less urine production when dehydrated.
• Kidneys regulate osmolarity by getting rid of solutes if there is an increase in solutes in the blood.
• Kidneys maintain ion balance by detecting and removing excess ions or conserving ions when levels are low.
• Kidneys work with the lungs to maintain body pH balance.
• Kidneys excrete wastes like urea, ammonia (breakdown products of protein & nucleic acids), and creatinine (breakdown product of creatine).
• Kidneys produce hormones like erythropoietin (for red blood cell maturation) and activate vitamin D.
• Kidneys perform gluconeogenesis i.e produce new glucose from non-carbohydrate sources

Anatomy of the Kidney

• Kidney receives blood from the renal artery which then flows through smaller vessels.
• Outer layer of the kidney, the cortex, appears granular.
• Inner layer, the medulla, looks striated.
• Nephrons have a ball-like structure in the cortex and a loopy structure dipping into the medulla.
• Renal pelvis, the hollow center, collects urine.
• Urine leaves the kidney through the ureter, leading to the bladder.
• Minor calyces in the medulla collect urine before it goes to the renal pelvis.
• Major calyces are formed when the minor calyces lead to one big funnel.
• The renal vein transports filtered blood out of the kidney.

The Nephron

• Functional unit of the kidney responsible for filtering blood and producing urine.
• Each kidney contains approximately one million nephrons.
• Nephrons cannot be replaced if damaged.
• Composed of the renal corpuscle (for blood filtration) and the tubule (for fluid processing).
• Fluid is called filtrate when it is inside the nephron.
• The tube selects which substances to keep, excrete, or add to the filtrate.

Nephron Anatomy

• Renal corpuscle is the big ball-like structure where blood is filtered into filtrate.
• The tube-like structure is called the tubule.
• Proximal tubule is the first section of the tubule.
• Loop of Henle is followed by the proximal tubule; it has a descending and ascending limb.
• Distal convoluted tubule is the twisted part of the tubule.
• Collecting duct is the last part of the tubule.
• Nephrons connect to the same collecting duct via branches.
• Typically, 4 to 5 nephrons connected to the same collecting duct.
• Once filtrate passes through the collecting duct, its composition cannot be altered.
• Minor calyces collect the filtrate, which then goes into the major calyces.
• The ascending limb of the loop of Henle passes by the corpuscle because the nephron twists around itself.

Cortical and Juxtamedullary Nephrons

• Cortical nephrons have a short loop of Henle while juxtamedullary nephrons have a long one
• Corpuscles are always located in the cortex.
• Cortical nephron corpuscles are in the upper part of the cortex, closer to the outside of the kidney.
• Juxtamedullary nephron corpuscles are in the lower part of the cortex, right beside the medulla.
• Blood vessels surrounding these nephron sets are different.
• Peritubular capillaries surround the tubule in cortical nephrons.
• Vasa recta surrounds the juxtamedullary nephron.
• Vasa recta reabsorbs filtrate and concentrates urine in juxtamedullary nephrons.
• 80% of nephrons in humans are cortical, and 20% are juxtamedullary.

The Renal Corpuscle

• Bowman's capsule is the outside layer.
• Bowman's space or capsular space is inside Bowman's capsule, where the filtrate collects.
• Glomerulus is a leaky capillary bed that filters fluid out of the blood.
• Podocytes wrap around the glomerulus to prevent leakage.
• Fluid filters in between the podocytes
• Afferent arteriole brings blood from the renal artery into each nephron.
• Efferent arteriole is the blood that exists the corpuscle.
• Juxtaglomerular apparatus is the connection where the last part of the ascending limb wraps around and goes between the afferent and efferent arterioles. Macula densa cells are specialized cells along the tube wall that can detect filtrate composition and give information to the corpuscle.
• These cells are part of last part of the ascending limb of the Loop of Henle.
• Juxtaglomerular cells are part of the afferent arteriole, they are specialized to release the enzyme Renin.

Renal Corpuscle Filtration Structures

• Glomerulus is a capillary bed with many pores called fenestrations, making it very leaky.
• Podocytes wrap around the leaky glomerulus and prevent some filtration.
• Podocytes are specialized cells of Bowman's capsule that directly touch the glomerulus, and are a continuation of Bowman's capsule.
• Basal lamina connects glomerulus to podocytes and prevent the filtration of larger items.
• The basal lamina is made of collagens and glycoproteins, and has a negative charge.

Barriers to Filtration

• The size of the pores determines what can pass from the blood into Bowman's space.
• Slit space is in-between podocytes where fluid moves and things can be dissolved.
• Basal lamina has spaces in between the collagens and negatively charged glycoproteins, which restricts some things from filtering out.
• To get from the blood into Bowman's pace, a substance must be small enough to go through the pores, small enough to go through the basal lamina, and small enough to travel in between the slit spaces of the podocytes.

What's in the Blood?

• Water is the solvent.
• Ions such as sodium, potassium, chloride, calcium, and magnesium.
• Proteins (small, big, and large).
• Hormones, oxygen, carbon dioxide, glucose, amino acids, red blood cells and white blood cells
• Water, sodium, potassium, calcium, and chloride.

What Can Get through the Barrier?

• Water molecules.
• Sodium, potassium, calcium, chloride.
• Glucose and amino acids.

What Cannot Get through the Barrier?

• Red blood cells and white blood cells.
• Proteins.

Blood Flow to the Kidneys

• 20% of cardiac output goes to the kidneys.
• Blood vessel organization from the heart to tissues: artery ~ arteriole ~ capillary (tissue bed for gas exchange) ~ venule ~ vein.
• Difference in blood flow in the kidney? Renal Artery brings blood to the kidney, but from there the afferent arteriole brings blood to the glomerulus

Blood Vessels around the Nephron

• Artery~ Capillary~ Efferent Arteriole system.
• Efferent arteriole takes the blood away
• Peritubular capillaries wraps around the tubule
• The kidney can control how much blood is being filtered because arterioles can constrict and dilate
• Peritubular capillary bed is responsible for reabsorption

Nephron Processes

• Filtration is from the blood in the glomerulus into Bowman's space.
• Reabsorption is from the filtrate in the tubule to the surrounding capillaries.
• Secretion is from the surrounding capillaries into the filtrate in the tubule.
• Excretion is the urine that is produced.

Glomerular Filtration

• Healthy kidneys produce 180 liters of filtrate per day
• This ability is due to several pressures in the renal corpuscle.
• Net Filtration Pressure is the sum of these forces
• Proper filtration occurs if net filtration pressure is about 10 mm Hg.

Forces

• Hydrostatic pressure (Pgc) pushes blood through the corpuscle.
• Colloid osmotic pressure (πgc) is from blood proteins that keep water nearby.
• Pressure from filtrate gets in way of new fluid being filtered (Pbc).
• Colloid osmotic pressure of bowman's capsule (πbc) allows stay water in space and attract more from glomerulus, assists filtration.

Calculating Net Filtration Pressure

• Net Filtration Pressure= (Pgc+πbc)- (Pbc+ πgc)
• Net Filtration Pressure= (55 mm Hg + 10 mm Hg) - (30 mm Hg +25 mm Hg) = 5 mm Hg
• Normal Net Filtration Pressure= 10 mm Hg
• Less fluid is filtered if the net filtration pressure is lower than usual
• Capillary bed could rupture if net filtration pressure was too high.

Glomerular Filtration Rate (GFR)

• The amount of fluid filtered in a day by the kidneys
• Normal value of 180 L/day (125 mL/min)
• Affected by net Filtration Pressure and filtration coefficient
• Filtration coefficient is affected by the spaces in between podocytes and permeability of the basal lamina.
• Two autoregulatory mechanisms functioning to keep GFR mostly constant: myogenic response and tubuloglomerular feedback.

Myogenic Response

• Afferent arteriole stretches with an increase in blood pressure
• This triggers stretch-sensitive ion channels to open
• Smooth muscle cells then depolarize
• Which allows Smooth muscle of the afferent arteriole to contract/constrict and blood flow decreases in the glomerulus

Tubuloglomerular Feedback

1. GFR decreases
2. Flow increases through tube
3. Flow increases past macula densa cells
4. Paracrine from macula densa reaches afferent arteriole
5. Afferent arteriole constricts
6. Resistance increases in afferent arteriole
7. Hydrostatic pressure in glomerulus decreases
8. GFR decreases

Regulation of GFR by blood flow

• GFR can be changed by constricting/dilating surrounding arterioles.
• Constricting afferent arteriole decreases blood flow into the glomerulus, decreasing hydrostatic pressure capillaries and thus decreasing the GFR.
• Vasoconstriction of the efferent arteriole increases the hydrostatic pressure of glomerulus which increases de GFR.
• Vasoconstriction of both the afferent and efferent arteriole decreases the GFR.

How to measure GFR?

• We can measure GFR by evaluating urine for a substance.
• Rate of of creatinine excretion from the body is equivalent to the GFR
• Excretion = Filtration- Reabsorption + Secretion

Measurements

• {Creatinine} plasma = 1 mg/L
• {Creatinine} urine= 90 mg/L
• Urine/day = 2L

Calculation

• {Creatinine} urine *urine/ day) / {Creatinine} plasma= 180 L/day= GFR
• (90 mg/L * 2L) / 1 mg/L = 180 L/day

How to measure GFR

• [Substance X] urine X Urine volume / [substance X] plasma

Renal Handling

• Filtered load calculates how much of a substance filter into Bowman's space in a day
• Determined by the concentration of that substance in the blood and the individuals GFR
• Filtered load X={X} plasma x GFR
• Renal handling determines/hypothesizes how much of that substance gets into the urine

Filtered Load of Glucose

• Filtered Load X= {X} plasma x GFR
• {glucose}plasma= 1 mg/mL
• GFR= 180 L/day or 125 mL/min
• Filtered load glucose= 1 mg/mL x 125 mL/min
• Filtered load glucose= 125 mg glucose excreted per minute
• All glucose that filtered should be reabsorbed so you should never find glucose in urine

Example Glucose

• Filtered Load X= {X} plasma x GFR Glucose} plasma= 1 mg/ mL
• GFR= 180 L/day or 125 mL/min
• Filtered load glucose= 1 mg/mL x 125 mL/min

How to calculate % Reabsorbed

• (Filtered load (day)- Amount Excreted)/ Filtered load (day)
• Water= 99% ; Sodium= 99.4% ; Glucose= 100% ; Urea= 50%

Overall Tubule Transport

• The proximal tubes main job is to reabsorb pretty much everything found in the filtrate
• It reabsorbs the most fluid(volume) found in the filtrate
• 65% of the total filtrate is reabsorbed in the proximal tube
• Water, ions (Na, K, Ca, Cl), glucose, and amino acids are reabsorbed in the proximal tube
• Henle absorbs 20% of the filtrate
• Ascending and Descending limbs reabsorb different things
• A descending limb reabsorbs water, whereas the ascending limb reabsorbs sodium, potassium, and chloride.
• Distal Convoluted tube and collecting tube reabsorb about 14% of filtrate volume together.
• Sodium, potassium, chloride, and calcium are reabsorbed in the distal convoluted tube.
• Collecting duct can reabsorb water and sodium are presence on hormones in the blood

Cells of the Tubule

• Tubule is a single layer of cellls called epithelial cells
• Inside the tubule is called lumen
• Outside the tubule we have blood vessels like peritubular capillaries and vasa recta
• Cells are polarized, meaning they look and act different on either side
• The inner side of the cell’s membrane is called luminal, whereas the outer side of the cell membrane is called basolateral.
• Reabsorption can happen two ways that are either paracellular or transcellular.
• Paracellular reabsorption occurs through the spaces between the cells, directly from the lumen to the interstitial fluid and then the blood vessels.
• Transcellular reabsorption occurs through the cells through the cell’s membrane

Proximal Tubule

• Sodium can move into the cells if there is a channel or transporter on the luminal membrane.
• Reabsorbs almost everything
• The only part of the neuron that contains the transporters to absorb glucose

Channel/transporter Table (Proximal Tubule)

• Na/Amino symporter, Na/Glucose symporter, Na/H exchanger, Na/K ATPase, Water Channel

Transcellular Reabsorption

• Second way reabsorption can happen is through cell through both cell’s membranes → transcellular absorption.
• Molecule has to pass these membrane by either, the molecules doesn’t have a problem crossing membrances or by a channel/transporter

Table of Luminal/Apical Membrane Transporters

• Na/amino acid symporter: sodium and amino acid bind for transport. Not responsive to hormones.
• Na/Glucose symporter: Sodium and Glucose bind to the carrier can move in the same direction. Not responsive to hormones
• Na/ H exchanger: sodium will move into cell and hydrogen will move into tubule if they are attached to carrier. Hydrogen gets secreted, and sodium gets observed. Responds to the hormone angiotensin II.
• Na/K ATPase: ATP is needed b/c both substances are being moved against concentration gradient. Purpose: to maintain a low concentration gradient inside our tube cells.
• Water channel: Water can easily pass through, Not responsiv to hormones

Water channel continue & Basolateral transporters

• Continue to the movement to water from inside the cell into the interstitial fluid then the blood

• Water will smoothly flow if solutes are going into the same direct.

• Aminoacid uniporter: the amino acids that brought into the cells can now be transported outside of the cells with any help

Glucose Uniporter

• Moving fron high→low concentration gradient
• Moving across membrane with protein carrier and no assitance fromm other ion
• Moving from cells→interstidial fluid

Paracellular H20, K, Cl

• Going inbetween the cells
• Water potassium, chloride→ reabsorbed between cells
• not reabsorbed by hhormones

Diabetes Mellitus

• Symptoms: glucose in urine, increased urine volume
• Incapable of reabsorbing all the glucose it was able to→ incresed amnounts of glucuse in bloodstream

Descending Limb of Loop of Henle

• Main role: absorb water
• Contains I and 2 which are not resposnsive to Hormones.
• Henle dips dewn into the medulla→ high itntertistional concentration increases→ water can easily move from the cells into the insterstitial fluid bc it contains concentration gradient

Ascending Limb of Loop of Henle

• Impermeable to water
• Ion reabsorption
• can allow paracellular transport in sodium specific (impermeable to water)

Distial Coveruted Tube

• Doesn’t reabsorb water and has no water channels
• no paracellular reaborstion
• Reaborstion the same ions as ascending limb
• calsicum reaborption hormonally regulated by parathyriod Hhormone (PTH)

List differece between ditital convoluted tubule and ascending Limb of henle.

• Reabsorption of calcium occurs in dtital convoluted tube
• paraceelular reaborpsion occurs in adencingg limb.
• PTH needed in digital convoluted tube.

Collecting Duct

• Conatins AquaporisII, III and I
• Aaquaporin II → reponsive to anitduertic (ADHhormone) adn Sodium channel on lumen channel→repsoncice to horomone 2

Regulation of water balance

• Increaseing in fluid inatke→ means increase in urine input

• Water balance controlled independently of salt balance in humans

• Urinbe balance could be as low as 0.4 L/day, as highh as 23/L dayy average =2/L/Day

Water Level and BLood Pressure

• Changes in the volume of blow=→ will effect blood pressure

• Kidneys controlling blood pressure thru ajusting the volume

• If towl water decreases→ extracellular fluid decreases→ decreased blood pressure

Anti Diuretic Hormone

• stimulus: low ECF volume, high plasma osmolarity

Actions of ADH

• Increase # aquaporin 2 channels on lumen membrane

• ADh will move→ receptor → cause

increase in aquarpoin 2 channels to move into lumnial membrane. which we call regulation of level becsue uou change the location of water hormones"

Water

• Increase in Plasma asmilairity cauase osmoreceptrs to shrivel→ causes ADh

Regulation Renin Release

• Low NA levels Detection of Low Sodium by → low blood pressure- baroreceptors. Low sodium- chemorceptors and are found in Mula densa cell

Atrial Natriertic Protein

• Relaeasee when there
• Higglevels

Actiin decrease sodiumreaborption by.

• Inhibit aodosteribe release
• Dialtrr the afferent artriole
• Lesser tube for Nate for reaborbstine

Physiology

• Increase of sodium with intake with instertines. More sodium caused cause an icnreast of osmarliry and the body will release ADH

ACID/base balance

• Normal plasma PH ≈ 7.4 →Lesser than 7→ ACIDIC condition would be called acidoses → higher thanr 7→ called alkaninotis and if body gets it calls it aloalosies

• Kidneys job→ help get rid from acidosis (molecules lowering pH) → conserve with in blood molecules ( give alkaine enevieronment)

Solutions → Mixture of acid + alkain components

• Proyons + hydrogong jons→ more acetic Bicarbotnaten = → more akiner→ to correct it kidneys get rid of protein and H CO-
• proximal tube: importnat with filter bicarbonatr →Intercalated cells (collecting cells).
• sodium hydrogem cells pumping H+ into tube. H+ attach to carbon atoms. Water eailsy traveals. The water and hydrogen will come otger with CA>

Section H plus secreting H3CO-Consvere filtered HCO-

• Atervicaue =. Sodium hydrogen cell pumping lots of hydrogen in the tubule. The tubule wull attach to the bibcrate travelling through the tubube to carbon and at. Wyer easily tavers out because the water membrane. Through cell water and a will for and h+ -the cell. Leoftover hydrogen cell will become secreter.

• type. A-found with in collection and acitivate when

• AN ATP PUMp -IS NECSSAEYY CUSE ITS ALRAT Hihj AMB]OUNT OF hudrogen in s the truvjle→ so theis is morring againet the conctenration

Respiratory and Rebreathing

• If u hve increase i and PH= → decrees in hydrogen ion-> To correct it the lungs slwos breathing rate.
• ph decrease = correct Qucik= decreaae carbon →lunsy and thid= is by hyperventiating Type and intercalcatey hco3- in the tubing.
• fount within collecting due . Acituvated in more biciacrtobale than in the cell in this situation . "Biacrbate. Getes. Secrtered cell and this happenes by using a porting carriger.

Type B Cells

• Found within the collecting duct.
• Activated with more bicabornate than visual.
• bicaebtr gets secreeed- from call with tumal Memrane→ and by carieer.
• rsepatrion CO 2 H> 10 can shift form a 1 form

Conclusion of Lecture

• In general these note cover renal physiology

Explore the vital functions of the kidneys, including regulation of fluid volume, blood pressure, osmolarity, and ion balance. Learn about waste excretion, hormone production, and gluconeogenesis. Understand the anatomy of the kidney, including blood supply and key structures.