Kidneys, Advanced Physiology

Receptor-Mediated Endocytosis: Plasma Proteins

Filtered Proteins are too big to be reabsorbed by carriers or through channels. When the proteins are digested in lysosomes the resulting amino acids are transported across the basolateral membrane and absorbed into the blood. The renal digestion of small filtered proteins is actually a significant method by which peptide signal molecules can be removed from the circulation

Myogenic Response

Intrinsic ability of vascular smooth muscle to respond to pressure changes. This is similar to autoregulation in other systemic arterioles - Increase Blood Flow - Increase Blood Pressure - Increase Stretch (sensed by mechoreceptors) - Vasoconstriction--> decrease in blood flow

If Renal Clearance = GFR

No net reabsorption, secretion, metabolism Inulin and Creatinine

Transepithelial Transport (reabsorption)

Substances cross apical and basolateral membranes of the tubule epithelial cells

Paracellular Pathway

Substances pass through the cell-cell junction between two adjacent cells

What are the vascular elements of the nephron

1. Afferent Arteriole - In the renal portal system, blood flows from renal arteries into an afferent arteriole 2. Glomerulus (Capillaries) - From the afferent arteriole, it goes into the first capillary bed, a ball-like network known as the glomerulus 3. Efferent arterioles - Blood leaving the glomerulus flows into an efferent arteriole 4. Peritubular capillaries - From the efferent arteriole the blood then goes into the second set of cappillaries called the peritubular capillaries

GFR Regulation

1. Calculating glomerular filtration pressure (Hydrostatic Pressure - colloid osmotic pressure - fluid pressure) = Net filtration 2. Autoregulation of glomerular filtration rates takes place over a wide range of blood pressures 3. Resistance chances in real arterioles alter renal blood flow and GFR 4. Vasoconstriction of the afferent arteriole increases resistance and decreases renal blood flow, capillary blood pressure (pH), and GFR 5. Increased resistance of efferent arteriole decreases renal blood flow but increases pH (hydrostatic pressure) and GFR

What drives filtration across the walls of the glomerular capillarie?

1. Hydrostatic pressure (Blood Pressure) - pressure of blood flowing through the glomerular capillaries forces fluid through the leaky endothelium - Capillary pressure: 55 mmHg and favors filtration into Bowman's Capsule - Filtration takes place along nearly the entire length of the glomerular capillaries 2. Colloid Osmotic pressure (proteins in the blood) - Inside glomerular capillaries is higher than that of the fluid in Bowman's Capsule. This pressure gradient is due to the presence of proteins in the plasma. The osmotic pressure gradient averages 30 mmHg and favors fluid movement back into the capillaries. 3. Fluid Pressure in Bowman's Capsule - Bowman's Capsule is enclosed space and so the presence of fluid in the capsule creates hydrostatic fluid pressure

What is the process with osmolarity changes as fluid flow goes through the nephron?

1. Isosmotic fluid leaving the proximal tubule becomes progressively more concentrated in the descending limb 2. Removal of solute in the thick ascending limb creates hyposmotic fluid 3. Permeability to water and solutes in the distal tubule and collecting duct is regulated by hormone 4. Final urine osmolarity depends on reabsorption in the collecting ducts

Filtration Fraction

1. Plasma Volume Entering afferent arteriole = 100% 2. 20% of plasma is filtered that passes through the glomerulus 3. > 19% of fluid is reabsorbed 4. > 99% of plasma entering kidney returns to systemic circulation 5. < 1% of volume is excreted to external environment Amount excreted = Amt filtered - amt reabsorbed + amount secreted

What are the functions of the Kidneys

1. Regulation of extracellular fluid volume and blood pressure 2. Regulation of osmolarity 3. Maintenance of ion balance 4. homeostatic regulation of pH 5. Excretion of wastes 6. Production of hormones

What are the tubular elements of the Nephron

1. Renal corpuscle (Glomerulus + Bowman's Capsule) -- Filtration of most protein-free plasma from the capillaries into the capsule 2. Proximal Tubule -- Isomotic reabsorption of organic nutrients, ions, and water. Secretion of metabolites and xenobiotic molecules such as PCN 3. Loop of Henle -- Descending (doing down), and Ascending (going up) -- Reabsorption of ions in excess of water to create dilute fluid in the luman -- Countercurrent arrangement contributes to concentrated interstitial fluid in the renal medulla 4. Distal nephron (Distal tubule + Collecting Ducts) -- Regulated reabsorption of ions and water for salt and water balance and pH homeostasis

Filtration Coefficient

1. Surface area of glomerular capillaries available for filtration: what is the surface area of the capillaries 2. Permeability of interface between the capillary and Bowman's Capsule: Are the filtration rate bigger or smaller?

Nephron

1. These are organized arrangement of microscopic tubules 2. they are functional units within the kidney and there are about 1 million of these tiny microscopic tubules 3. The renal corpuscle contains glomerulus and Bowman's capsule 4. The tubule (looks like tubes attached to a head shape) contains the proximal tubule, loop of Henle, distal tubule and collecting ducts 5. Parts of these tubules will dip into the medulla of the kidney

What is the process in which vasopressin causes insertion of water pores into the apical membrane

1. Vasopressin binds to membrane receptors 2. Receptor activates cAMP second messager system 3. Cell inserts AQP2 water pores into apical membrane 4. water is absorbed by osmosis into the blood

Anatomy of the Urinary System

2 Kidneys - located retroperitoneally at the level of the lower ribs 2 Ureters 1 bladder 1 urethra

Transport Maximum

At substrate concentrations equal to or above the saturation point, transport occurs at a maximum rate

Antidiuretic Hormone (ADH)

Control of vasopressin Secretion 1. Secreted by posterior pituitary 2. Stimuli for secretion -- Decrease in blood pressure: Carotid and aortic baroreceptors -- Decrease atrial stretch due to low blood volume: atrial stretch receptor -- osmolarity greater than 280 mOsM: Hypothalmic osmoreceptors

Why doesn't water moving out of tubule dilute high osmolarity?

Countercurrent exchange in the vasa recta 1. Filtrate entering the descending limb becomes progressively more concentrated as it loses water. 2. Blood in the vasa recta removes water leaving the loop of Henle 3. The ascending limb pumps out Na+, K+, and Cl-, and filtrate becomes hyposmotic

What would be the response to a decrease in blood pressure and decrease in volume

Decrease in blood pressure and volume 1. Volume receptors in atria and carotid and aortic baroreceptors would trigger homeostatic reflexes 2. Cardiovascular System: Increase cardiac output, and vacoconstrict 3. Behavior: increase thirst causes water intake, this would increase ECF and ICF volume 4. Both cardiovascular system and Behavior would increase blood pressure 5. Kidneys: conserve water to minimize further volume loss

Active transport of Sodium

Epithelial Na+ channel (ENAC) 1. Na+ enters cell through various membrane proteins, moving down its electrochemical gradient 2. Na+ is pumped out the basolateral side of cell by the Na+-K+-ATPase

Excretion Rate

Excretion = Filtration - Reabsorption + Secretion

Medullary Interstitium

High solute concentration is only partly due to NaCl. - Half the solute in this compartment is urea - Membrane transporters for urea are present in the collecting duct and loops of Henle - One family of transporters consists of facilitated diffusion carriers, and the other family has Na+- dependent secondary active transporters - These urea transporters help concentrate urea where it contributes to the high interstitial osmolarity

Net Filtration

Hydrostatic Pressure (pH) - Colloid Osomtic Pressure - Pfluid pressure = Net Filtration

What makes urine dilute?

In the absence of vasopressin, the collecting duct is impermeable to water which makes urine dilute

If Renal Clearance < (less than) GFR

Net reabsorption Glucose, amino acids.

If Renal Clearance > (greater than) GFR

Net secretion K+ and H+

Excretion (Kidney Function)

Once the filtered fluid (now called filtrate) passes into the lumen of the nephron, it becomes part of the body's external environment, just as substances in the luman of the GI tract are part of the external environment. Anything that filters into the nephron is destined for removal in the urine, unless it is reabsorbed into the body.

Tubuloglomerular Feedback Process

Process 1. GFR Increases 2. Flow through tubule increases 3. flow past macula densa increases 4. paracrine from macula densa to afferent arteriole 5. Afferent arteriole constricts 6. Resistance in afferent arteriole increases 7. Hydrostatic pressure in glomerulus decreases 8. GFR decreases

Secondary Active Transport

Symport with Sodium 1. Na+ moving down its electrochemical gradient uses the SGLT protein to pull glucose into the cell against its concentration gradient 2. Glucose diffuses out the basolateral side of the cell using the GLUT protein 3. Na+pumped out by Na+-K+-ATPase

Filtration Barriers

The renal corpuscle contains this type of barrier, there are Three types: 1. Capillary endothelium- first barrier 2. Basal Lamina- Second barrier 3. Podocytes- third barrier

Saturation

The maximum rate of transport that occurs when all available carriers are occupied by substrate Consequences: Glucose reabsorption in the nephron. At normal plasma glucose concentration, all glucose that enters the nephron is reabsorbed before it reaches the end of the proximal tubule. The tubule epithelium is well suppied with carriers to capture glucose as the filtrate flows past. Blood glucose becomes too high, glucose is filtered faster than the carriers can reabsorb and the carriers become over saturated and are unable to reabsorb all the glucose therefore the glucose escapes and is excreted in the urine

Filtration (Kidney Function)

The movement of fluid from blood into the lumen of the nephron. This takes place only in the renal corpuscle, where the walls of glomerular capillaries and Bowman's capsule are modified to allow bulk flow of fluid. -- Once the filtered fluid (filtrate) passes into the lumen of the nephron, it becomes part of the body's external environment

Passive reabsorption: Urea

The nitrogenous wast product has no active transporters in the proximal tubule but can move through the epithelial junctions by diffusion if there is a filtrate and extracellular fluid are equal When Na+ and other solutes are reabsorbed from the proximal tubule, the transfer of osmotically active particles makes the extracellular fluid more concentrated than the filtrate remaining in the lumen When water is reabsorbed, the concentration of urea in the lumen increases- the same amount of urea is contained in the smaller volume. Once the urea is moved out of the lumen into the extracellular fluid by transport through the cells or the paracellular pathway.

Micturition

The process of urination - urine does not change composition, the process is as follows 1. Stretch receptors fire 2. Parasympathetic neurons fire, motor neurons stop firing. (centers in the brain stem and cerebral cortex override basic reflexes under the parasympathetic control) 3. Smooth muscle contracts. Internal sphincter is passively pulled open. External sphincter relaxes

What type of signaling mechanism is the Tubuglomerular Feedback

This is a paracrine signaling mechanism through which changes in fluid flow through the loop of Henle influence the the GFR - The juxtaglomerular apparatus consists of macula densa and granular cells -- The granular cells secrete renin, an enzyme involed in salt and water balance -- When NaCl delivery past the macula dena increases as a reult of increased GFR, the macula densa cells send a pararine message to the neighboring afferent arteriole and the affernt arteriole constricts, increasing the resistance and decreasing the GFR

Capillary Endothelium (Filtration Barrier)

This is the first filtration barrier - Glomerular capillaries are fenestrated capillaries with large pores that allow most components of the plasma to filter through the endothelium.

Excretion (urine output)

This is the process in which urine is the result of all the processes that take place in the kidney This process rate depends on 1. the filtration rate of the substance 2. whether the substance is reabsorbed, secreted, or both as it passes through the tubule

Basal Lamina (Filtration Barrier)

This is the second filtration barrier - an acellular layer of extracellular matrix that separates the capillary endothelium from the epithelium of Bowman's Capsule. - consists of negatively charged glycoproteins, collagen, and other proteins - This acts like a coarse sieve, excluding most plasma proteins from the fluid that filters through it.

Podocytes (Filtration Barrier)

This is the third filtration barrier - These have a long cytoplasmic extension called foot processes that extend from the main cell body - These surround each capillary, leaving slits through which filtration takes place. Mesangial cells between the capillaries contract to alter blood flow

Secretion in the Kidney's

This is the transfer of molecules from extracellular fluid into the lumen of the nephron K+ and H+ by the distal nephron is important in the homeostatic regulation of those ions. This function enables the nephron to enhance excretion of a substance. This process is an active process because it requires moving substrates against their concentration gradients. Most organic compounds are secreted across the proximal tubule epithelium into the lumen by indirect active transport

Secretion (Kidney Function)

This selectively removes molecules from the blood and adds them to the filtrate in the tubule luman. This process is more selective process that usually uses membrane proteins to move molecules across the tubule epithelium.

Organic Anion Transporter (OAT)

This type of transporter is considered a tertiary active transporter and transports a wide variety of endogenous and exogenous anions - bile salts - benzoate used as a preservative in soft drinks - salicylate from aspirin - Saccharine- artificial sweetener Process of OAT 1. the proximal tuble cells uses ATP to maintain the low intracellular concentration of Na+ 2. The Na+ gradient is then used to concentrate a dicarboxylate inside the tubule cell using Na+ dicarboxylate cotransporter called the NaDC 3. The NaDC is found on both apical and basolateral membrane in the proximal tubule

Filtered Load

Total amount of substances (S) filtered into Bowman's space per unit time Filtered Load of S = GFR X [S]plasma Example: GFR = 180 L/day [Na]plasma = 3.5 g/Liter Na+ filtered load = 180 L/day x 3.5 g/Liter = 630 g/day

Glomerular Filtration Rate (GFR)

Volume of fluid that filters into Bowman's Capsule per unit time 1. Rate is relatively constant 180 L/Day 2. Influenced by two factors - Net filtration factors - Filtration coefficient

What makes Urine Concentrated?

With maximal vasopressin, the collecting ducts is freely permeable to water. Water leaves by osmosis and is carried away by the vasa recta capillaries

Inulin

polysaccharide isolated from the tuberous roots of a variety of plants (this is considered the same as insulin in humans). This is considered a noninvasive way to measure GFR (measurement to for kidney function)

Reabsorption (Kidney Function)

the process of moving substances in the filtrate from the luman of the tubules back into the blood flowing through peritubular capillaries

Aquaporins

these are Water pores 1. membrane channels with at least 10 different isoforms that occur in mammalian tissues. The kidney has multiple isoforms of aquaporins including aquaporin-2, the water channel regulated by vasopressin

Autoregulation of GFR

this is a local control process in which the kidney maintains a relatively constant GFR in the face of normal fluctuations in blood pressure - Important function of this autoregulation process is the protection of the filtration barriers from high blood pressures that might damage them.

Clearance (excretion)

this is a solute that is the rate at which that solute disappears from the body by excretion or by metabolism For any solute that is cleared only by renal excretion, clearance is expressed as the volume of plasma passing through the kidneys that has been totally cleared of that solute in a given period of time Once you know the GFR, you can determine how kidney handles solutes This method helps determine renal handling by comparing filtererd load of solute by excretion 1. Inulin Clearance: is equal to GFR 2. Glucose Clearance: Noramly all glucose that filters is reabsorbed 3. Urea Clearance (net reabsorption)- if filtration is greater than excretion, there is net reabsorption 4. Penicillin clearance (net secretion): if excretion is greater than filtration, there is net secretion

What would be the response to a increase in blood pressure and volume

volume receptors in the atria, endocrine cells in atria, and cartoid and aortic baroreceptors would trigger homeostatic reflexes 1. Cardiovascular System: Decrease output and vasodilate 2. Kidneys: excrete salts and water in urine and there would be a decrease in ECF and ICF volume