Renal System Overview

Renal System Overview

• Kidneys are responsible for various functions, including regulating plasma volume, removing waste, balancing electrolytes, and regulating acid-base balance.
• These functions result from selective reabsorption and secretion of various molecules within the kidney.

Kidney Structure

• The urinary system comprises macroscopic and microscopic components.
• The microscopic structure includes glomerular filtration, including glomerular filtration rate and regulation, and mechanisms of salt and water reabsorption for water balance, Na/K balance, and acid-base balance.

Mammalian Kidney

• The mammalian kidney features a nephron, renal pelvis, renal pyramid, cortex, and medulla.

Nephron Types

• Two main types of nephrons exist: cortical nephrons (most common) with short loops of Henle, and juxtamedullary nephrons with long loops of Henle.
• The length of the loop of Henle affects the kidney's ability to concentrate urine.

Kidney Tubules

• Kidney tubules are made of epithelial cells, which have a brush border, tight junctions, and apical and basolateral surfaces.

Urine Formation

• Urine formation involves three key processes: filtration, reabsorption, and secretion.

Glomerular Filtration Properties

• Filtration in the Bowman's capsule includes water, salts, glucose, urea, and amino acids.
• Blood cells and most proteins are not filtered.
• The filtrate is driven by glomerular pressure.

Glomerular Filtration Dependence

• Glomerular filtration relies on net filtration pressure and the structure of the glomerular endothelium, Bowman's capsule, and the basement membrane.
• Fenestrated capillaries, filtration slits in the Bowman's capsule, and negative charges on the basement membrane are important factors.

Juxtaglomerular Apparatus

• The juxtaglomerular apparatus consists of the distal tubule, Bowman's capsule, the glomerular capillaries, afferent and efferent arterioles as well as the granular cells and macula densa.

Glomerular Filtration Rate (GFR)

• GFR is measured in mL/min or L/day.
• It is typically 120 mL/min (180 L/day) in healthy adults, and is equivalent to filtering about 5.5 liters every 40 minutes

GFR Regulation

• Renal blood flow (RBF) is a key factor in determining GFR.
• RBF is closely regulated to maintain a relatively constant GFR in the face of changes in arterial blood pressure (between 80 to 200 mm Hg).
• Changes in RBF or GFR are detected and adjusted within the kidney itself through myogenic and tubuloglomerular feedback mechanisms.

Intrinsic GFR Regulation

• Myogenic regulation involves smooth muscle contraction in the afferent arteriole in response to stretch in the glomerulus to regulate GFR.
• Tubuloglomerular feedback involves changes in glomerular blood flow affecting the distal tubule's macula densa to alter the release of chemical messengers for regulating GFR.

Extrinsic GFR Regulation

• The sympathetic nervous system can increase or decrease renal blood flow, altering GFR.
• Hormones like angiotensin II and aldosterone can alter GFR by affecting blood volume or blood pressure.

Mechanisms of Salt & Water Reabsorption

• Different nephron segments possess varying ion transport mechanisms and permeabilities to water.
• This sets up different conditions within the nephron for reabsorbing essential materials and eliminating harmful waste products.

Proximal Convoluted Tubule

• Reabsorption in the proximal tubule involves the active transport of sodium, potassium, and chloride ions.
• Glucose, amino acids, and phosphates are reabsorbed via secondary active transport mechanisms.

Loop of Henle

• The juxtamedullary nephron has more of an impact than cortical nephrons in the salt & water reabsorption process.
• About 20% of salt and water is reabsorbed, not regulated.
• The countercurrent multiplier system is involved in reabsorption.

Thin Descending Limb

• The thin descending limb is highly permeable to water but has low permeability to ions.
• Water reabsorption occurs in response to the osmotic gradient produced by the loop of Henle.

Thick Ascending Limb

• The thick ascending limb actively transports sodium, potassium, and chloride ions from the filtrate into the interstitial fluid surrounding the nephron.

Distal Convoluted Tubule

• The distal convoluted tubule performs essential functions: maintaining electrolyte balance (sodium, potassium) and acid-base balance.

Counter Current Multiplier Significance

• Loops of Henle play a critical role in establishing an osmotic gradient in the renal medulla.
• Longer loops create a steeper gradient, enabling higher urine concentration.

Vasa Recta Significance

• The vasa recta helps maintain the osmotic gradient by recirculating fluids and salts, trapping these substances within the interstitial tissues of the kidney.

Collecting Duct

• The collecting duct plays a role in fine-tuning salt and water reabsorption, and this process is regulated by hormones such as antidiuretic hormone (ADH).
• In the collecting duct, the last 10-15% of filtrate is reabsorbed.

Renal Control of Electrolyte Balance

• Approximately 85-90% of sodium and potassium is reabsorbed in the proximal tubule and loop of Henle independently of hormones.
• The remaining 10-15% is regulated by aldosterone and occurs mainly in the distal convoluted tubule (DCT).
  • Aldosterone affects sodium reabsorption and potassium secretion.
  • Several hypotheses explain sodium absorption mechanisms.
  • Increased potassium secretion is thought to involve increased synthesis of potassium channels in the apical membrane

Acid-Base Balance

• The kidney plays a role in mammals, working alongside other regulatory mechanisms for the regulation of plasma pH. It regulates H+ and HCO3- concentrations both in the plasma and in the filtrate
• pH regulation occurs inside the DCT and collecting ducts by A and B cells
• When urine pH is below 4.5, the secretion of H+ is inhibited

ADH Mechanism

• ADH is secreted in responses to low blood pressure or high osmolarity.
• ADH binds to a GPCR on the collecting duct cells.
• This leads to the exocytosis of aquaporins, resulting in increased water permeability and increased water reabsorption.

Aquaporins

• Aquaporins form channels allowing water to move across the membranes of the collecting ducts.