Renal Physiology: Kidney Function

Renal Physiology

• The kidneys maintain homeostasis by regulating electrolyte composition, volume, osmolarity, and pH of the internal environment.
• Kidneys eliminate waste products from bodily metabolism except carbon dioxide.
• Useful substances like glucose and phosphates are conserved, while metabolic wastes and excess salt/water are eliminated via urine.
• Module 04 explores kidney anatomy, physiology, and role in balancing water, sodium, plasma, electrolytes, glucose, and phosphate.

Module 04 Learning Outcomes

• Describe the major structures of a juxtamedullary nephron and discuss the importance of each section with respect to reabsorption and secretion.
• Describe blood flow through the kidneys and its physiological importance in the generation of urine.
• Describe how the kidney can make urine either more dilute or more concentrated than other bodily fluids, using your knowledge of osmotic gradients.
• Describe the physiological responses that occur to dehydration in order to reduce water loss through urine production.

Major Fluid Compartments

• Intracellular Fluid (ICF) is the fluid within cells, comprising about two thirds of total body fluid.
• Extracellular Fluid (ECF) surrounds cells, including plasma, interstitial fluid, lymph, and transcellular fluid, and is about one third of total body fluid.
• Plasma (one fifth of the ECF) and interstitial fluid (four fifths of the ECF) are key pools.
• Lymph and transcellular fluid are considered negligible

Barriers Between Body Fluid Compartments

• Several barriers separate the body-fluid compartments, limiting water and solute movement.
• Plasma and interstitial fluid are separated by blood vessel walls; water (except proteins) can freely exchange at capillaries, making their compositions essentially identical.
• Intracellular fluid and ECF are separated by the plasma membrane that does not exchange proteins.

ECF Volume and Osmolarity

• Overall fluid balance depends upon regulating the ECF.
• The two factors that regulated are ECF volume and osmolarity.
• ECF volume is regulated to maintain blood pressure, salt balance is also very important to regulate
• ECF osmolarity is regulated to prevent cell swelling or shrinkage.

Control of ECF Volume

• ECF volume affects blood pressure by changing plasma volume.
• Increasing ECF volume increases plasma volume and arterial blood pressure resulting in mechanisms to adjust blood pressure until ECF volume returns to normal.
• Mechanisms:
  • Baroreceptor Reflex:
    • Baroreceptors detect changes in arterial blood pressure; when pressure falls, cardiac output and total peripheral resistance increase, when blood pressure rises, both decrease.
  • Fluid Shifts:
    • A decrease in plasma volume can temporarily be compensated for by fluid shifting out of the interstitial compartment into the plasma.
    • An increase in plasma volume can cause fluid to shift to the interstitial compartment.

Long-Term Control Factors of ECF Volume

• Consist of fluid input and output
• The kidneys control fluid output
• The thirst mechanisms control fluid input
• Long-term regulation of blood pressure relies on kidney control of urine output alongside the thirst mechanism controlling fluid input.

Control of Salt

• Sodium and associated anions (mainly chloride) account for over 90% of ECF solutes.
• Water follows salt due to osmosis therefore, controlling salt levels controls ECF volume.
• Salt input must equal salt output to maintain salt balance.
• Poor regulation of salt input depends on dietary salt; daily replacement of salt lost in feces and sweat is necessary.
• Excess salt output occurs in the kidneys, which primarily regulate sodium excretion.

Hypotonicity of the ECF

• Usually associated with overhydration
• Three major causes
  • Renal Failure: Those afflicted are not able to produce a concentrated urine.
  • Rapid Water Ingestion: Occurs in healthy individuals who take in large volumes of water exceeding the kidney's capacity.
  • Over Secretion of Vasopressin: Vasopressin promotes water retention.
• Regulating osmolarity prevents undesirable water shifts into or out of cells.

Hypertonicity

• Hypertonicity in the ECF, characterized by an excessive concentration of ECF solutes, is usually linked to dehydration and stems from 3 main causes:
  • Insufficient water intake/ not drinking enough
  • Diabetes insipidus: deficiency in vasopressin
  • Excessive water loss: Heavy sweating during extreme exercise, prolonged bouts of vomiting, or diarrhea.
• Consequences relate to decreased normal cell function due to reduced ICF volume; confusion, delirium, coma, or even death can occur.

Isotonic Fluids

• Have equal osmolarity to that of normal body fluids.
• Administered directly into the blood plasma, which makes up approximately one fifth of the ECF.
• When isotonic fluid is injected into the ECF compartment, the ECF volume increases but solute concentration remains unchanged.

Regulation of Water Balance

• Hypothalamic osmoreceptors constantly monitor fluid osmolarity for quick response.
  • Increased osmolarity triggers vasopressin secretion and thirst.
  • Decreased osmolarity inhibits vasopressin secretion and thirst.
• Vasopressin acts on the kidneys to increase water reabsorption, while thirst stimulates water intake.
• Large losses of ECF volume activate left atrial volume receptors which the stimulate hypothalamic pathways to stimulate thirst and vasopressin release.

Overview of the Kidneys

• Kidneys are controlled by neural and endocrine inputs.
• Kidneys maintain ECF volume, electrolyte composition, and osmolarity
• With excess water or specific electrolytes, kidneys increase elimination; kidneys cannot actively correct deficits but can reduce elimination.

Primary Kidney Functions

• Water balance
• Body fluid osmolarity
• Plasma volume
• Acid-base balance
• ECF solutes regulation
• Waste excretion
• Foreign compound excretion
• Erythropoietin production
• Renin production
• Vitamin D activation

Kidney Structure

• Bean-shaped organs, each about 10 cm in length.
• Each has an adrenal gland on top.
• Consist of renal cortex (outside) and renal medulla (inner part).
• The renal pelvis is the inner core through which urine empties into the ureter.
• The nephron is the kidney's functional unit, with over a million in each adult kidney.
• Blood is filtered within nephrons to produce urine and reabsorb necessary fluids and molecules.

Nephron Vascular Component

• Supplies blood to the nephron.
• Glomerulus: ball-like capillary where water and solutes are filtered from plasma.
• Renal artery divides into afferent arterioles, each supplying a nephron.
• Efferent arterioles transport unfiltered blood from glomerulus.
• Peritubular capillaries deliver oxygen to tissues since nephron capillaries receive and then release arterial blood with no oxygen extracted.

The Tubular Component (Nephron)

• A hollow tube transports urine to the renal pelvis.
• The tubular component consists of:
  • Bowman's capsule: Encircles the glomerulus and collects filtrate.
  • Proximal tubule: coiled within the renal cortex
  • Loop of Henle: Hairpin loop descending into the medulla and ascending back to cortex.
  • Juxtaglomerular apparatus: ascending limb passes between afferent and efferent arterioles.
  • Distal tubule: Coiled again entirely. Drains into collecting duct.
  • Collecting duct: travels into the medulla and drains into the renal pelvis.

Types of Nephrons

• Cortical Nephrons
  • Located in the outer layer of the cortex and serves primarily secretory and regulatory functions (80% of nephrons),
  • Loop of Henle only slightly dips into the renal medulla.
  • The peritubular capillaries wrap around the short loops of Henle.
• Juxtamedullary Nephrons
  • Found on the inner layer of the cortex and are responsible for concentrating/diluting urine.
  • Peritubular capillaries form vasa recta which are in close proximity to the long loops of Henle.

Blood Flow Through the Nephron

• Renal Artery
• Afferent Arteriole
• Glomerulus
• Efferent Arteriole
• Peritubular Capillaries
• Renal Vein

Basic Renal Processes

• Glomerular Filtration (GF): 20% of blood that flows through glomerular capillaries is filtered into Bowman's capsule (plasma filtrate without proteins).
• Tubular Reabsorption (TR): Important substances are returned to the peritubular capillaries (178.5 liters of 180 liters reabsorbed).
• Tubular Secretion (TS): Substances are transferred from peritubular capillaries into the tubules for excretion in urine, allows excretion the substance of the remaining 80% of plasma that hasn't been filtered.

Kidneys Main Functions

• Water balance
• Bodily fluid osmolarity
• Regulate ECF solutes
• Regulate plasma volume
• Excrete wastes
• Secrete erythropoietin, renin, activate vitamin D, and maintain acid-base balance

Comparing Nephrons

• Cortical nephrons:
  • Lies in outer layer of cortex.
  • Serve primarily secretory and regulatory functions.
  • Accounts for 80% of all nephrons.
  • Has a Loop of Henle that only slightly dips into renal medulla.
• Juxtamedullary nephrons:
  • Resides in inner layer of cortex.
  • Responsible for urine concentration and dilution.
  • Vasa recta are found in proximity to the long loops of Henle

Glomerular Filtration

• Blood is filtered across capillary walls through the glomerular membrane into Bowman's capsule, then filtrate enters nephron tubule.
• Blood to the glomerulus is supplied by an afferent arteriole and exists via an efferent arteriole.
• The glomerular filtration rate (GFR) measures the rate at which blood is filtered through all glomeruli.

Glomerular Membrane Layers

• Capillary Wall: Single layer of endothelial cells, with pores which are 100x permeable to fluids and solutes than regular capillaries.
• Basement Membrane: No cells and contains collagen and glycoproteins to provide structural strength and discourages filtration of plasma proteins .
• Bowman's Capsule Inner Layer: Consists of podocytes forming narrow filtration slits for fluid to pass.

Forces Regulate Glomerular Filtration

• Glomerular Capillary Blood Pressure:
  • Blood pressure in glomerular capillaries is normally higher due to afferent diameter larger than efferent preventing pressure from decreasing
  • Glomerular capillary pressure is on average 55 mmHg
• Plasma Colloid Osmotic Pressure:
  • Large proteins in plasma that cannot be filtered resists water movement
  • Plasma-colloid oncotic pressure is about 30 mmHg.
• Bowman's Capsule Hydrostatic Pressure
  • Pressure of filtrate within Bowman's capsule which resists water moving out of glomerular capillaries
  • Bowman's capsule hydrostatic pressure is around 15 mmHg.

Net Filtration Pressure

• Net Filtration Pressure equals Glomerular Capillary Blood Pressure MINUS Plasma-Colloid Oncotic Pressure PLUS Bowman's Capsule Hydrostatic Pressure.
  • Net Filtration Pressure = 55 mmHg - (30 mmHg + 15 mmHg) = 10 mmHg
• In an average male, this value is 125 ml/min, and in females it is 115 ml/min!
• GFR depends on filtration pressure, available surface area, and membrane permeability
• These factors collectively are known as the filtration coefficient (Kr).
• Filtration Coefficient (Kf) x Filtration Pressure = Glomerular Filtration Rate

Uncontrolled Influences on GFR

• Plasma-colloid osmotic and Bowman's capsule hydrostatic pressures do not vary much, but pathological conditions can alter both factors.
  • Kidney stones obstructing the ureter can lead to increased hydrostatic pressure to decrease GFR.
  • Diarrhea/dehydration decreasing blood pressure with increased plasma-colloid osmotic pressure resulting in decreased GFR.

Equations to Determine Filtration

• Net Filtration Pressure: Glomerular Capillary Blood Pressure - (Plasma-colloid Oncotic Pressure + Bowman's Capsule Hydrostatic Pressure)
• Glomerular Filtration Rate (GFR): Filtration Coefficient (K+) x Net Filtration Pressure
• Autoregulatory mechanisms are in place to prevent sudden swings in GFR because changes in GFR are directly proportional to glomerular capillary blood pressure.

Intrinsic Mechanisms that Happens in Autoregulation (Intrinsic)

• Regulate arteriole diameter to prevent swings in GFR.
  • If afferent arterioles are constricted will decrease glomerular capillary blood pressure/dilating will increase it.
• Two intrarenal mechanisms:
  • Myogenic activity:
    • Increased pressure on afferent arteriole walls leads to automatic constriction reducing blood flow to glomerular capillaries thus prevents GFR increase
    • The opposite is also true/lower blood pressure will lead to arterial dilation and increase GFR, thus vasoconstriction prevents blood
  • Tubuloglomerular Feedback (TGF):
    • Macula densa sense changes of salt levels in the tubular fluid; increases in arterial pressure which raises which will allows more fluid to go through the tubules.
    • Macula Densa releases ATP which turns to adenosine which then causes the afferent arterioles to constrict and reduce GFR again.

GFR Regulation

• Vasoconstriction - decreases glomerular capillary blood pressure, net filtration pressure, and glomerular filtration rate.
• Vasodilation - increases glomerular capillary blood pressure, net filtration pressure, and glomerular filtration rate

Extrinsic GFR Control

• Independent of fluctuations in blood pressure and controlled by the sympathetic nervous system.
• During hemmorhage, baroreceptors sense the drop in blood volume and initiate responses to normalize blood pressure.
• Sympathetic activity constricts afferent arterioles which reduces GFR and urine production, the mechanism which depleted plasma volumes are corrected.

The Kidneys and Cardiac Output

• The kidneys do not deliver oxygen and nutrients only, but "clean" the blood.
• In a healthy person, 20% of plasma goes into kidneys and becomes glomerular filtrate
  • If Glomerular Filtration Rate is 125ml/minute, total blood flow to the kidneys must be 625mL per minute (5x125).

Tubular Reabsorption

• Glomerular filtrate is identical to plasma (no selectivity).
• The kidneys are able to maintain tight control of water and electrolyte concentrations of the body in order to eliminate waste efficiently.
• Tubular Reabsorption will return water and crucial solutes back into the plasma/ allowing some waste products to remain.
• The process of Reabsorption is a Two Step Process
  • Substances from the tubule into interstitial space (active/passive movement)
  • passive movements from interstitial space and back into the blood stream/plasma

Fate of various substances filtered by the Kidney's

• Tubular reabsorption is selective/variable, high reabsorption capacity if body needs the substance/low if it doesn't.

General Trends of Tubular Reabsorption

• Water 99 average percentage filtered substance reabsorbed and a 1 average percentage filtered substance excreted
• Sodium: 99.5 average % substance reabsorbed and 0.5 % average % of substance excreted
• Glucose 100% average % substance reabsorbed/0 average percentage% substance excreted
• Urea 50 % average % substance reabsorbed and average percentage% substance excreted is 50 % average % substance reabsorbed
• Phenol: average % substance reabsorbed is zero/average/percentage substance excreted is 100 %.

Transepithelial Transport

• Transport of solutes across an epithelial cell layer through the cell.
• Substance that enters epithelial cells cannot transport to a neighboring cell as membranes of neighboring epithelial cells are not in contact beside tight junctions.
• In Transepithelial Transport, substance must move through the cell into interstitial space.
• Steps involved in Transepithelial Transport:
  • Cross the luminal membrane.
  • Must pass through the cytosol.
  • Cross the basolateral membrane.
  • Diffuse through the interstitial fluid.
  • Cross the capillary wall to enter the plasma

Active and Passive Transport

• The Reabsorption of Sodium is both active/passive
• Na passively moves across the luminal membrane
• Uses the Sodium/Potassium/ATP pump/active transport
• In the Proximal tubule 76% of the Sodium is Reabsorbed, needed for reabsorption of amino acids,glucose,chloride, urea and water
• In the ascending limb of the loop of henle 25% the sodium is henle
• In the Distal and Collecting tubules sodium are under hormonal control 8%(regulates volume as well secretion/absorption of hydrogen as well sodium)volume as well secretion/absorption of hydrogen as well sodium
  • The loop of henle absorbs 25% of the total reabsorbed.
  • Ascending Limb of the loop of herble sodium and chloride are needed

Hormonal Regulation of Sodium

The most important and well-known the hormone is sodium and the renin hormone and sodium

• Three primary Triggers of Retention of sodium (RAAS) - The granulator cells are sensitive to the sodium and also when/If sodium decreases that will trigger the granule cells trigger to secrete Sodium/renin - The granulated pressure that is sensitive blood(granule cells/pressure sodium) - Secretes renin is when granulated/decrease the blood pressure - granulated release sodium when increases

Active and Passive Transport

• Renin sodium: This is what controls and allows a series of events to occur (Sodiums balance)
• Series of events
• Sodium : An enzyme that converts to agnotism
• Agniotesim - Pass through the blood and are converted in the lungs
• Hormone/sodium - Causes kidneys,absorb sodium and also is caused by hormone

Actions of Aldosterone

• Influences the insertion of cells and carries the sodium channel in the Luminal Membrane(sodium potassium AT Pace)
• This is when it results on greater Sodium channel out of the tubule fluid

Atrial Natriuretic Peptide

• Nat and Water's main actions are opposite to aldosterone
• Released the decrease of sodium/volume - Inhibit Sodium, reabsorption/more sodium,excreted through the urine - Renin and aldosterone/Sodium decrease - sodium dilation all more sodium to be excreted - Hormonal and regulation Sodium

Active Transport

• Substances to move the tube transported with carrier
• Because the Number protein. membrane is limited then the limitation of the transport maximum.

Transport Maximum

• Plasma,Sodium: The volume concentration fluid excreted/the urine
• Is called the threshold
  • The sodium and this carries this carriers. limitation
  • Concentration'Plasma concentration is regulated to the kidney and then/however it is important

Glucose and the Sodium

• Plasma concentrations aren't a normal. Normal 100 milligram in 125 Millimeters filtration

Chloride H20 and Urea

Pump for reabsorption of

• not there it's it's just passive
• reabsorption water/choline/urea: Is passively passive that goes to reabsorbed along with Sodium
• Sodium : Will go to the distal parts to see. the influence are to sodium of both a state body
• Water : H 20 channels in. distal for always open/vasopressin isn't always open

  • (Diuretics/H20). plasma sodium is is does not and produce sodium strong drive from what Sodium strong sodium

    - Electrolyte levels 
       : Kidneys doesn't regulate which is chloride
              - Electrolytes with Sodium =Determends electrolyte and sodium reabsorbed 
                    sodium
    

UREA

• Doesn'T net and diffuse/fluid water
• To reabsorb in kidney/renal failure where all measurement levels clinically(plasma-blood tests)

Tubular Secretion

• Opposite of tubular reabsorption (done by transcellular transport).
• Moves substances from peritubular capillaries into tubule lumen.
• Helps remove substances from the body.
  • Hydrogren ios can be secreted in the proximal/distal as well collecting tubules to see if more Hydrogen is needed depending on the needs of the body
• More hydrogens/less to help base:H secretion that helps body balance Sodium/Kal and sodium
• Kal can have has both tubular reabsorption an tubal reabsorbed to go into prox(Kal)to make sure glomerulus is free when and then activated into tubular
• distal tubules/tubal(H)(AT Pace Kal): Sodium will transfer from into to change to potassium/hydrogen also potassium

Effects on the Body

• Low/high potassium: Secretion and factors with change the rate/potssiom
• Balance: Plasma to affect the adrenal gland/aldosterone (sodium secretion). relationship plasma/stimulation (depletion)

Acidosis Affects

• SodiumK ATP;distal/k sections (nephron)/limited pumps
• Plasma increase/H potassium passively tube
• LessKal levels Inappropriate

Electrolyte Levels Reabsorb

• Cattails: Prox/distal two are (anion)/(cation)
• Anion:Increasing more
• Organs Blood Increasing:Chemical order- histamine

The Nephrons Functionality

• Soluble SolublePoor-
• Enters Filtrates: Smaller:Can't carrier
• Hormone-to enter in plasma

Transport

• Anions: Food in in the organs

Functionalities are Maintained

• proximal/distal/sodium

Plasma Membranes

• 12mm Sodium active reabsorbs.
• The reabsorbed are sodium hormone, sodium. This what balances the hormone.

Plasma/Kidney

• Filtration's mm.Hormone and kidney. If. Hormone,Sodium,hormone and kidneys

###Plasma and Kidneys. • Filtrate balance to hormone

Urine the kidney.

• Sodium. Is volume Is volume :Vertical

vertical : Loops

Is loops loop. Anatomic

Gradient/Osmolarity Gradient

A.

• loop Is loop with the water/loop and (vasta)
• Loop :Sodium and water

Water is the fluid/H20

• If dehydration to high
• If low to sodium are also high
• Electrolyte is with also sodium. Always the same if if vasopressin and the hydration body If hydration to reabsorb this means vasopression is. the. more reabsorption of Vasopressinhomrone

Micturition

• Bladder transport if to bladder is full
• If: Nerve and the bladder

External Micturition

A.

• Not skeletal and voluntary.
• The is voluntary
• Reflex: Voluntary reflex
• This in (adult). Normal ml

17. Spine to stimulates. To and releases. Sphiniceter for
18. It's In is reflex(babies release urine)!

Important Hormone

• 13/14 is is is is 4 and it is electrolytes

19. Osmolarity'Is to and the are and the

Learning 4 outcomes

1. Prox are. are and to reabsorption and