BMS250 - Wk 9

Major Body Fluid Compartments

• The body consists of 60% or more water, an average of 40L.
• Intracellular fluid makes up 2/3 of the total body water (27 L).
• Extracellular fluid is 1/3 the total body water.
• Blood plasma is a small portion of extracellular fluid, only about 3 L, or 20% of ECF.
• Interstitial fluid comprises 80% of the ECF which is approximately 10-11 L.
• Added fluid or salt to the bloodstream spreads freely between the extracellular spaces, with variable diffusion to the intracellular space.
• Ionic constituents vary significantly between intracellular and extracellular compartments.

ECF vs. ICF

• Addition of water expands both ECF and ICF compartments.
• Addition of isotonic saline expands the ECF compartment.
• Additional of salt without water expands the ECF but shrinks the ICF.

General Cellular Transport Mechanisms

• Nephron tubules transport water, solutes, wastes, and biologically important filtered substances using transport mechanisms.
• Major transport mechanisms include: Passive diffusion, facilitated diffusion, active transport, secondary active transport (symport/antiport), endocytosis, and exocytosis.
• These mechanisms enable nephrons to reabsorb essential substances (water, glucose, amino acids, ions) and secrete wastes into the tubular lumen for urine excretion.
• Regulation of these processes maintains fluid, electrolyte balance, pH and osmolarity.

Passive Diffusion

• Molecules move across the tubular epithelium down the concentration gradient.
• No energy expenditure.
• Used in the movement of lipid-soluble substances, small ions, and gases across cell membranes.
• Water and lipid-soluble substances such as urea can passively move through the lipid bilayer of tubular epithelial cells.

Facilitated Diffusion

• Molecules cross the cell membrane using specific carrier proteins or channels.
• This process depends on the concentration gradient and and does not require direct input of energy.
• Common molecules include glucose and amino acids are transported.

Active Transport

• Active transport involves moving molecules against the concentration gradient.
• Requiring energy from ATP.
• Carrier proteins such as pumps facilitate the process.
• A crucial active transporter, the Na+/K+-ATPase pump in the nephron.
• It actively transports sodium ions out of tubular epithelial cells into the interstitium and pumps potassium ions into the cell.
• It establishes a sodium concentration gradient to reabsorb other substances.

Secondary Active Transport (Symport and Antiport)

• Secondary active transport is the coupled movement of two or more molecules.
• Molecules move across the cell membrane.
• Symport mechanism: molecules move in the same direction.
• Antiport mechanism: molecules move in opposite directions.
• The sodium-glucose cotransporter (SGLT) is a symport example.
• Sodium and glucose ions are co-transported into tubular epithelial cells.
• The sodium-calcium exchanger is an antiport example.
• Sodium ions move into the cell, while calcium ions move out.
• Bicarbonate generated within the cell is transported into the interstitium via an Na-3HCO3 symporter.
• Hydrogen ions are secreted via a Na-H antiporter.

Endocytosis and Exocytosis

• Endocytosis engulfs extracellular substances by invaginating the cell membrane to form vesicles.
• Exocytosis is the reverse process, where vesicles release their contents into the extracellular space by fusing with the cell membrane.
• Less common in renal tubules, however, these processes uptake or secrete large molecules or particles.

Ionic Constituents of Intracellular vs. Extracellular Solutes

• Approximate ICF and ECF concentrations of Na+, K+, Cl-, and HCO3- should be known.

Routes of Water Gain and Loss

• Insensible water loss occurs without awareness.
• Insensible water losses from the skin are separate from sweating.
• Water intake and loss are tightly regulated.
• The cardio-renal system does the final “tuning”.

Water Gain and Loss in Adults (mL/day)

• Water intake: Beverage (1200), Food (1000), Metabolic (350), total (2550).
• Water output: Insensible (900), Sweat (50), Feces (100), Urine (1500), total (2550).

Basic Renal Reabsorption

• Renal tubules transport substances via two routes: transcellular and paracellular.
• Transcellular route: Apical surface -> cytoplasm -> basolateral surface -> peritubular capillaries (or vasa recta).
• Paracellular route: Moves across tight junctions and into the ECF between adjacent cells.

Histologic Tubule Overview

• PCT: simple cuboidal epithelium, lots of microvilli, and many mitochondria.
• Loop of Henle (thin limbs): simple squamous epithelium, few mitochondria.
• Loop of Henle (thick limb): cuboidal epithelium, few microvilli, lots of mitochondria.
• DCT: simple cuboidal epithelium and some microvilli.
• Collecting tubules: principal and intercalated cells (simple cuboidal epithelium).

Tubule Function

• PCT function: reabsorption of nutrients and ~60% of water/solutes.
• Loop of Henle (thin limbs) function: passive water absorption (descending) or NaCl absorption (ascending).
• Loop of Henle (thick limb) Function: establishes ionic gradient for countercurrent multiplication dilutes urine, and makes interstitium hypertonic.
• DCT function: Na+, Cl-, and water balance.
• Collecting tubules function: principal cells regulate absorption of Na+, water, K+ and intercalated cells regulate acid/base and K+ homeostasis.

Handling of Sodium

• Water makes up the major fraction of the body volume, and is specifically contained in the blood volume.
• Sodium and chloride contribute most to the osmotic content of the extracellular fluid and osmolality.
• Sodium and chloride movements are linked for electroneutrality, where cation movement requires equivalent anion movement.
• Approximately 60% of body weight is water, distributed across aqueous spaces based on osmotic content.
• Intracellular fluid (ICF) has roughly two-thirds of body's osmotic content and two-thirds of the water.
• Extracellular fluid (ECF) is one-third of the osmotic content and water; mostly interstitial fluid (three-fourths of ECF), and blood plasma (one-fourth of ECF).
• Water crosses most cell membranes easily, ECF and ICF are in osmotic equilibrium.
• Altered volumes are due to water gain/loss, and relative volume differs with sodium and other solute gain/loss.
• Sodium additions or losses are primarily to/from ECF, and cellular Na-K-ATPases prevent major intracellular sodium concentration changes.

Sodium, Chloride, and Water Transport

• Excretory rates for sodium, chloride, and water vary extensively.
• Water and salt are freely filterable at the renal corpuscle and undergo considerable tubular reabsorption.
• Water: Always reabsorbed; never secreted, water moves from lower to higher osmolality.
• Water reabsorption follows solute reabsorption since some kidney regions have the epithelium with low H2O permeability.
• Chloride transport involves more steps and is passive.
• Chloride transport is tied to sodium transport to maintain electroneutrality.
• The proximal tubule reabsorbs approximately two-thirds of filtered sodium, chloride, and water.
• Sodium transport is linked to other substances and is regulated at different points in the tubule by multiple controls.
• The kidney handles sodium with filtration, reabsorption, and secretion to maintain electrolyte balance, blood pressure, and overall homeostasis.
• Roughly 65% of sodium and water are reabsorbed in the proximal tubule.
• Descending thin limb of Henle's loop reabsorbs 10% of water.
• Thin ascending and thick ascending limbs of Henle's loop reabsorb 25% of sodium.
• Distal convoluted tubule reabsorbs 5% of sodium.
• Collecting-duct system reabsorbs 4-5% of sodium and also 5% (during water-loading) / >24% (during dehydration) of water.
• Principal cells reabsorb sodium; intercalated cells - acid/base and K+ homeostasis.
• The body nearly completely reabsorbs sodium, most is done by the proximal tubules and all descending limps of the Henle.
• The remaining 10% is reabsorbed with Physiological Reabsorption and Homeostatic Regulation.
• The essential event for active transcellular sodium reabsorption is the transportation from cell to interstitial fluid by Na-K-ATPase pumps at the basolateral membrane.
• These pumps keep lower intracellular sodium concentrations.
• There is a larger, inwardly-directed osmotic force for sodium which means it passively moves into symport/antiport/ H2O channels.

Chloride Reabsorption

• The tubular locations for reabsorbing chloride, and the reabsorbed percentage are simailar to sodium.
• Any volume of fluid must contain equal amounts anion and cation equivalents.
• A litre of normal filtrate contains 140 mEq of sodium and about 140 mEq of anions, 110 mEq chloride and 24 mEq bicarbonate.
• More than 60% of the filtered chloride is reabsorbed in the proximal tubule.
• Later segments account for as much as 40%.
• Active transcellular chloride reabsorption needs transport of chloride from lumen to cell.
• The chloride transport process must go against potential and needs enough intracellular ion concentration.
• Luminal membrane chloride transporters do the same thing that the basolateral membrane Na-K-ATPase pumps do for sodium.
• To excrete water in excess of salt, kidneys separate solute and water reabsorption.
• Water reabsorption is parallel to salt reabsorption in the proximal tubule (~65% of both), but differs beyond the loop of Henle.
• Water is reabsorbed in descending portions and sodium is reabsorbed in the ascending loop. This means that the fraction of sodium resbed is greater.

Water

• Amount of water depends, in the different components of the cellular gradients.
• Water reabsorption is done mainly from the aquaporins in the plasma of the cells, and in others the tight junctions between cells.
• Luminal membrane of the epithelium of the descending limps is permeable and the early part of the loop.
• Intracellular or cytosilic ormolality is always closed to that of surround intersitum.
• The water permeability as well as the membranes of the tubular systems and tubules of convoluted tubes that are far remain relatively impermaeable.

PCT (Proximal Convoluted Tubule)

• Here, carbon dixoide and bicarbonate are handled as elegant transport with carbonic anhydase and reabsorption through several steps.
• Primarily uses Carbonic Anhydrase to reabsorb Bicarbonate, Sodium and Water.
• Another form is done via ATI and Method 2.
• The PCT reabsorbs ~ 6~70% of most solutes, but that can be greater.
• PCT Reabsorbs 805 Bicarbonate.
• The mechanism used Transcellular and Paracellular mechanisms.
• Follows Positive Charge from Sodium.
• There are two major methods of reabsorption done in the PCT called 1 and 2.
• Both involve the uses of ATP, H=, H+ base base, H2O CI from Sodium at the apex of both mechanism. Base also allows h and CI, as well as H2O2 CI being more and move to follow that gradient through the use of ATP.
• It maintains the ionic nature with it.

Nephron Detailed Function

• The PCT reabsorbs nutrients and fluids and blood (electrolytes, glucose, proteins, and amino acids, chloride, potassiuim and so on.
• Some transporters are more active, and glucose will activate the co-transporter, with several in effect.
• They are reabsorbed by the sodium.
• They are more and less effective and some have co-transporters like ATII.
• There is a reabsoption of 70% and 15 - 10% later after the PCT.
• Later parts are not very permeable.
• The cells are also very permeable and the molecules are easy and fast to do those gradients.
• There are different components of the tubules and loops.
• These functions also work between the vas recta and tubules.
• Water is 80% while amino acids are nearly none.

Organic reabsorption (albumin)

• If there is no Reabsorption happens in the PC< then the cells go to the urine and are lost.
• The transporters can move up to 100 Species.
• The ones are taken up used and degraded before being transported throughout with no reabsorption later.

Glucose & SGLT

• Glucose is brought in with sodium and family from there being on the other side.
• So it creates that osmotic push through.
• A good example of a uniporters for the membrane.
• This is to avoid the waste
• SGLT2 isoform, responsible for most glucose reabsorption ■ In the late proximal tubule the stoichiometry is two-for-one SGLT-1 isoform.

Solute Secretion

• There is the table on the table and side of it.
• The most in the cells make organic cells and more effective.
• They bind with versatile.
• Cations and Anion transporters

Principal Cells of Collecting Tubules

• The principal cells are specialized epithelial cells found in distal convoluted tubule and the collecting ducts.
• These principal cells regulate sodium (Na) and water transport.
• These cells are affected by aldosterone.
• The sodium is primarily resbed.
• This causes channels that allow a gradient.
• After a cell binds and enhances then increasing the Na to pull it through.

Aquaporin

• Sodium channels helps to create the osmotic flow for a sodium reabsortion.
• Aldosterone and Na is a trigger for this process.

Collecting Ducts

• There is a central role with that and the hormone influence it.
• Aldosterone makes it very effective from both processes.

Dilute vs Concentrated Urine:

• Involves complex processes within the kidney.
• Most has to deal with the different counter exchanges and loops.

Countercurrent

• Depends on the loop with descending having water and sodium having potassium.

multiplier

• Allows amplifications with sodium to get more water via as a result.

Hypothalamic

• Blood pressure flows influence.
• The vasocontrition has more retention.

ADH

• Controls with more water with the collecting ducts.
• Results in Concentralized Urine

NKCC

HairPin

• Structuring from these helps in their function.
• Also depends on hormone production that helps in the kidney reabsorb.

The Renin-Angiotensin-Aldosterone System.

-This acts as the major regulator of renal sodium output.

• It modulates vasco tone.
• This is impacted due to the level of sodium.
• The level of sodium is inversely proportional.
• JG are in part of renal afferent Arterials.
• Renal has systemic circulation and intra-arterol renal.

RAAS

• The system is for Aldo Sterone this called RAAS.
• Protien substrate is the AT. The enzyme that turns it to 1. Further enzymes make less peptides.
• Receptors bind them ATII makes then and also makes aldosterone.
• Aldo stimulates the production of the system is the overall impact

AT II System

• Makes ATs which need to be converted.
• the amount of renin is the amount of active agent
• Juta produces the AT which is on afferent end close to the granular JGA or J cell granules.
• It inversely with sodium

The Release of

• Input sympathetic by 3 means..
• Inhibit Input has more renal and so forth..
• Arterial pressure has release which changes.
• Sympathetic is influenced for cardion and the pressure changes to JG
• There are many cells acting as receptors they sense to.

More receptors

• the JG sense drops to make release and increase to reduce.
• The other arterial senses, signal center stimulation release

Macula Densa

• The amount of output affects other products, such as the JG to prevent release, AT's are reduced and levels and that allows that to go higher out and into filtration of sodium
• if there is too little the NG and AT will release and allow back into flow. Increased.

Hormones

• ATI, releases ATP, then flows into a loop to affect water.
• Epinephrine to vasoconstic
• Norephinferne also causes some release
• AND is tissue overload and to reverse this will decrease.

Key Actions

• AT 2 is a preservation method to increase.
• It reduces and raises AT1

Vasocontrict

• Vascular pressure has also a pressure problem this reduces to sodium.

Tubulars

• stimulates reabsorb by AT1
• And releases Chloride to control sodium.

Aldo

• is a stimulant.
• is good in low and low.
• can be a steroid.

Calcium and Phosphate

• These also have factors but with a more involved path.
• They depend on these loops.
• they play that part.
• They are in paracellular or intercellular ways
• But there are more for sodium levels.

The Thick Loop

• But they don't absorb much at all.

DCT CNT

• That's fine and very important.

CD

• All small but important for what hormones.
• The excess water causes then to excrete Phosphate in the influence of growth factors.

Buffer Systems

• Bodies balance through buffer system.
• the systems do with those ions on the list.

Types of systems

• The is several systems for this.

Acid and BASE