Glomerular Filtration & Renal Blood Flow

Glomerular Filtration, Renal Blood Flow, & their Control

Objectives

• Glomerular filtration rate (GFR) needs to be defined and understood.
• The clinical significance of GFR as a measure of kidney function needs to be explained.
• Factors influencing GFR, including blood flow and filtration membrane properties, need to be identified.
• The autoregulation of GFR and renal blood flow needs to be described.
• The myogenic response and tubuloglomerular feedback mechanisms need to be explained.
• Understanding how autoregulatory mechanisms maintain stable GFR despite fluctuations in blood pressure is important.
• Hormonal and neural control of glomerular filtration need to be discussed.
• The role of hormones (e.g., angiotensin II, prostaglandins) in regulating GFR needs to be described.

Elements of Renal Function

• Kidney functions include the formation of urine and participation in the balance of osmolarity and volume.
• Body fluid osmolality is regulated by determining how much solutes are present in circulation.
• Solute regulation occurs through increased secretion or reabsorption (Na, Cl).
• Body fluid osmolality is the amount of solutes dissolved in a solution, with a normal plasma osmolarity of 300 mOsm.
• Dehydration leads to loss of water in plasma, increasing plasma osmolarity; the kidney responds by increasing reabsorption and decreasing fluid elimination.
• Overhydration, from ingesting too many fluids increases plasma volume; the kidney tries to maintain blood volume of 5L, increasing urine formation.
• Electrolyte balance is regulated by transporting important solutes (Na, K, Cl). Ability of nephron segments to increase reabsorption or secretion of solutes.
• The kidney regulates acid-base balance. When plasma pH decreases, indicating high H concentration, the kidneys increase H elimination/secretion and bicarbonate (HCO3) reabsorption.
• When plasma pH increases, with low H concentration, the kidneys decrease H elimination/secretion and increase HCO3 elimination
• Kidneys are the sole means of eliminating certain acids from protein metabolism (sulfuric acid, phosphoric acid).
• Metabolic products and foreign substances are excreted by the kidney.
• Some metabolic byproducts of medications are eliminated through urine. A drug test detects drugs that can impede with driving.
• The kidney secretes hormones such as erythropoietin, calcitriol, and renin. Erythropoietin (EPO) stimulates RBC formation by hematopoietic stem cells in bone marrow.
  • Patients undergoing dialysis often have kidney failure and reduced EPO production, leading to anemia, which is then treated with EPO supplementation.
• Calcitriol (1,25-dihydroxyvitamin D3) is the active form of vitamin D, necessary for normal Ca absorption by the Gl tract, deposition in bones, and phosphate regulation. Production is impaired in patients with kidney disease.
• Renin is an enzyme that catalyzes the conversion of angiotensinogen to angiotensin I in the RAAS system, regulating blood pressure as well as N and K balance.

Structural Anatomy of the Human Kidney

• Cortex: outer region
• Medulla: inner region
• Nephrons are in the cortex and medulla including: Cortical, medullary and juxtamedullary.
• Nephron location plays a role in its ability to form concentrated/dilute tubular fluid.
• the concentration of solutes in the interstitium increases when going from cortex to medulla due to the nephron segment's ability dilute or concentrate the tubular fluid.
• Osmolarity increases due to accumulation of solutes being reabsorbed by nephron segments.
• Increased osmotic pool attracts water from tubular fluid.
• Some tubular fluid from nephrons empties into the calyx.
• Fluid filtered by the calyx has already been processed.
• Due to gradient which result in a hyperosmolar medullary interstitium, the fluid/urine empties out to the ureters.
• Na and Cl enter the cell across the apical membrane through the Na/H (NHE3) and Cl base antiporters. Secreted H and base combine in tubular fluid to form an H-base complex which can recycle.
• Accumulation of H-base complex in tubular fluid establishes an H-base concentration gradient that favors H-base recycling across the apical plasma membrane into the cell.
• Inside the cell, H and the base disassociate and recycle back across the apical plasma membrane.
• Reabsorption of Na is dependent on Na/K ATPase localized to basolateral membrane.
• There is uptake of NaCl across the apical membrane.
• Glucose is also reabsorbed and exits the cell across the basolateral membrane via GLUT1 rather than via GLUT2 (as in first half of Proximal Convoluted Tubule (PCT).
• 67% of sodium is reabsorbed in the PCT = 67% of water reabsorbed, due to the presence of brush border.
  • Sodium and other solute reabsorption increases into the lateral intercellular space, decreasing tubular fluid osmolality. Water then flows by osmosis across the tight junctions and PCT cells → hydrostatic pressure increases in the lateral intercellular space fluids move into the capillaries.
• How is water reabsorbed in PCT?
• NaCl is reabsorbed either by paracellular or transcellular pathway, as NaCl leaves tubular fluid and enters the paracellular space, the osmolarity of paracellular spaces increases.
• Water becomes attracted to increased osmolarity of paracellular spaces.
• Water from the tubular fluid moves into lateral intercellular space. Hydrostatic pressure increases as the water enters the lateral intercellular space → tubular fluid moves towards the circulation.

Protein Reabsorption in Proximal Convoluted Tubule (PCT)

• Proteins are not normally found in urine. Almost 100% of proteins are reabsorbed in PCT by enzymes in apical membrane of PCT cells that degrade proteins and convert them into amino acids through protein endocytosis & intracellular breakdown.
• Amino acids leaves the cell via basolateral membrane and goes into the capillary circulation.
• Some proteins that becomes part of the glomerular filtrate are reabsorbed. Proteins → Amino acids → Circulation.
• Rich protein intake can overwhelm, resulting in presence of proteins in tubular fluid that were not reabsorbed leading to positive protein findings in urinalysis, This may result in acute glomerulonephritis where proteins are filtered freely due to damage in filtration barrier.

Nephron

• The nephron is the functional unit of the kidney. About 1.2M nephrons are found in one kidney, making 2.4M for a pair of kidneys.
• It consists of a renal corpuscle, proximal tubule, loop of Henle, distal tubule, and collecting duct system.
• The Proximal Tubule is found in the cortical area. They are cells with brush borders for absorption, processing 67%.
• The Descending Thin Limb (DTL) is concentrating segment, water permeable and solute impermeable. Water is reabsorbed.
• Ascending Thin Limb (ATL) & Thick Ascending Limb (TAL) diluting segment. Water impermeable, solute permeable. Solutes are reabsorbed.
• The osmolality decreases as it dilutes the tubular fluid. In the Distal Tubule & Collecting Duct, permeability will depend on presence/absence of antidiuretic hormone (ADH). Essentially water impermeable with need to ADH.
• Impermeability can be affected by cellular properties and the presence of a particular factor. Fluid moves because of the concentration gradient, meaning osmolality in the interstitium should be higher.
• Nephrons may be subdivided into Cortical/superficial nephrons and Juxtamedullary nephrons.
• Cortical (Superficial) Nephrons: They make up majority of nephrons. For every 1 juxtamedullary nephrons, 10 cortical nephrons.
• Located at outer region of cortex, small segment that extends deeper into the medulla.
• Associated efferent arterioles branch into peritubular capillaries that surround segments.
• Juxtamedullary Nephrons have longer loop of Henle and extend deeper into medulla.
• Efferent arteriole forms not only a network of peritubular capillaries but also the vasa recta. Vasa recta descend into medulla and form capillary networks. Surrounds collecting ducts and ascending limbs of the loop of Henle.
• 0.7% of RBF in vasa recta, slow blood flow (function for more exchange/interaction of molecules). When fast, water enters general circulation.
• Functions: Conveying oxygen and metabolic substrate to support nephron function, delivering substances to nephron for secretion, and serving as a pathway for return of reabsorbed water & concentrating and diluting urine.

Renal Corpuscle

• A renal corpuscle is composed of an afferent arteriole, efferent arteriole, glomerulus, and macula densa.
• Glomerulus: Formed through merging of afferent and efferent arterioles that 3 layers which negatively charged.
• Mechanism: Blood enters the glomerular capillaries from the afferent arterioles filtration commences unfiltered blood enters the efferent arterioles. Highly sensitive to Sodium Chloride (NaCl) concentration in TAL
• According to Berne and Levy, it is part of TAL.
• Contains special transporters abundantly found within TAL including; 1Na/1K/2Cl symporter.

Mechanism

• Blood enters afferent arteriole moves towards glomerulus filtration begins and ultrafiltrate will then be collected within Bowman's space which then enters the proximal tubular (as tubular fluid).
• Blood from glomerulus moves towards efferent arterioles peritubular capillaries and vasa recta.
• Podocytes specialized group of cells which covers the glomerulus.
• Important role in filtration of fluid, blood, and plasma.
• In the cases of glomerulonephritis, there is inflammation of the glomerulus negative charge is lost you may see proteins and blood in their urine since they can enter the filtration barrier since no repelling force edema exhibit: there is lower oncotic pressure and higher hydrostatic pressure fluid goes to the interstitium management: diuretics, albumin (acts to increase oncotic pressure).
• Glomerulus supplied in afferent and efferent arterioles.

Filtration Barrier

• In post-streptococcal Glomerulonephritis: Occurs after patient recovers from streptococcal infection (commonly children).
• Patients develop glomerulonephritis after having streptococcal infection: Edema in lower extremities, puffy eye (reason: endotoxins were deposited within kidneys bacterial inflammations).

Functions

• Made up of mesangial cells and mesangial that forms a supportive structure.
• Extraglomerular mesangial located outside glomerulus phagocytic indirectly influence the cleanliness rate of filtration/blood pressure.
• The Glomerular Filtration Barrier allows water, electrolytes and small molecules to pass blood cells inside the circulation. Driven by starling.
  • In glomerulonephritis: an endothelial barrier resulting to inflammation. dysfunctional resulting in flatten filtration and RBC's and proteins
• -> proteins in urine.

Ultrafiltration

• Fluid is collected in Bowman’s space where not all passes is filtered.
• Barrier - Ensures essential waste while water electrolyte. Regulate Reabsorption of Electrolytes

Factors That Adjust Filtration Are

• Afferent
• Efferent
• Systemic

Dynamics of Ultrafiltration

• First water - glomerulus.
• Comp osition - Water Electrolytes.

Renal Blood Flow

• Fine Tune Through Fine Tuning.

Inulin

• Gold Standard for measuring GFR.
• Indications. how well, Precise filtering ability, what volume if needed.

Creatinine

• Used to measure.
• It a balance or measures the blood flow.
• Side effect decreases and effects Kidney levels.

Filtration Rate