Juxtaglomerular Apparatus (JGA)

Juxtaglomerular Apparatus (JGA)

• The JGA is where the distal convoluted tubule (DCT) meets the afferent arteriole
• The two main cell types release renin

Granular Cells

• Also called Juxtaglomerular cells
• Located in the afferent arteriole
• These cells have smooth muscle
• They function as mechanoreceptors sensitive to blood pressure

Macula Densa Cells

• Found in the DCT
• Serve as chemoreceptors that respond to changes in osmolarity, particularly of Na+

Renin Release and Blood Pressure

• Renin release decreases when blood pressure is high
• Renin release increases when blood pressure is low
• Renin is a proteolytic enzyme secreted into the bloodstream

Renin-Angiotensin System

• Renin converts renin substrate (produced by the liver) into angiotensin I
• Angiotensin I converts to angiotensin II in the lungs via ACE

Angiotensin II Functions

• Stimulates aldosterone and antidiuretic hormone (ADH) secretion
• Causes vascular smooth muscle constriction
• Stimulates the sympathetic nervous system
• Promotes thirst and drinking, increases blood pressure and volume

Low Blood Volume Effects on Macula Densa Cells

• Less Na+ passes by these cells if there is low blood volume or filtration pressure
• They stimulate renin release, increasing blood volume and Na+ retention
• This action promotes vasodilation of the afferent arteriole, increasing glomerular filtration and tubular volume

Tubuloglomerular Feedback

• Macula densa cells respond to high GFP pressure or high Na+ content in the filtrate
• Macula densa cells release ATP to constrict the afferent arteriole
• The result is a decreased glomerular filtration pressure and rate

Tubular Reabsorption

• Filtrate enters the proximal convoluted tubule (PCT), reabsorbing the greatest amount of fluid
• The PCT quickly reclaims much of the tubule's content, returning them to the blood
• Reabsorbed materials pass from the PCT into peritubular capillaries

Active vs. Passive Transport

• Active transport uses ATP and moves substances against their concentration gradient, conserving useful substances like glucose, amino acids, vitamins, and ions
• Passive transport uses the concentration gradient, diffusion, facilitated diffusion, and osmosis
• Passive transport pulls substances into the PCT via osmotic pressure
• Urea is 50% reabsorbed and 50% stays in the filtrate, while water, Cl-, sulfate, nitrate, and creatine are passively reabsorbed

Factors Affecting Reabsorption

• Active reabsorption is limited by carrier availability, energy, and the amount of work cells can perform
• Normally, all filtered glucose is absorbed; none is excreted
• In hyperglycemia, glycosuria occurs as glucose enters the PCT faster than cells can process it; polyuria results when there is excess urine output

Urine Formation Step 2

• Most of the filtrate is reabsorbed into the blood
• Tubular reabsorption reclaims most of the tubule contents and returns them to the blood, beginning as soon as the filtrate enters the PCT

Proximal Convoluted Tubule (PCT) Function

• The PCT is the most active reabsorber
• It normally absorbs all glucose and amino acids in the filtrate and 65% of Na+ and water
• Nearly all uric acid and half of urea are reabsorbed in the PCT

Nephron Loop Function

• Water reabsorption is not coupled to solute reabsorption
• The descending limb does not have solute reabsorption
• The descending limb contains scarce aquaporins
• No solute reabsorption occurs in the descending limb

Ascending Limb Function

• The thin segment of the ascending limb has Na+ moving down the concentration gradient
• The thick segment performs most solute reabsorption

Distal Convoluted Tubule (DCT)

• Hormones are active in the DCT
• Here, a small amount of filtered load is subject to fine-tuning
• Antidiuretic hormone (ADH) increases water reabsorption
• ADH makes collecting duct cells more permeable to water by inserting aquaporins into their apical membrane
• ADH regulates the amount of water reabsorbed

Aldosterone Functions

• Holds Na+ and releases K+
• The secretion of aldosterone by the adrenal cortex is encouraged by decreased BP or increased K+ levels
• Enhances Na+ reabsorption, increasing BP and BV
• Water follows Na+ when aquaporins are present

Other Hormones

• Atrial natriuretic peptide (ANP) reduces blood Na+ and BP/BV
• Parathyroid Hormone (PTH) increases Ca2+ reabsorption and also causes phosphate excretion in PCT

Tubular Reabsorption of Sodium

• Na+ is the most abundant cation in the filtrate
• About 80% of energy is used for Na+ reabsorption, which is usually always active via a transcellular route
• Primary active transport occurs at the basolateral membrane, with secondary active transport at the apical surface

Transport Maximum

• Used for almost every substance reabsorbed using a transport protein in the membrane
• When transports are saturated, the excess is secreted into urine
• Having plasma levels with glucose exceeding 180 mg/dl results in large amounts of glucose lost in urine

Tubular Secretion

• Materials are secreted from the blood capillary into the nephron lumen by tubule cells, in both PCT and DCT
• Actively secretes drugs, excess H+, K+, and ions
• Deamination of amino acids results in excretion of H+ ions (NH3 + H+ → NH4+)
• Bicarbonate ions act as buffers to prevent dramatic changes

Concentrated Urine Formation

• Juxtamedullary nephrons with longer loops of Henle aid concentrated urine formation
• The medullary gradient during infancy is essential
• The anatomical organization of blood vessels (vasa recta) is essential
• Countercurrent multiplier system in the loop of Henle allows this to happen
• Permeability of collecting duct is important

Loop of Henle

• The loop is asymmetrical
• The descending limb contains thin cells and is permeable to water
• The ascending limb contains thick cells and is impermeable to water; it actively pumps out Na+ and Cl- to intercellular spaces in the kidney medulla

Countercurrent Exchange

• This requires two columns close to each other that run parallel in opposite directions
• As the blood capillary descends into the kidney medulla, it picks up salt and loses water
• As the blood capillary ascends, it picks up water and gives back salt
• Blood that goes in and exits the medulla has the same ionic composition
• The ionic gradient in the kidney medulla is maintained.

Countercurrent Multiplier

• Ions are actively pumped out of the ascending limb of the loop of Henle
• The concentration of ions inside the nephron increases as it gets deeper
• Materials move into the extracellular space, concentrating salts in the medulla
• Movement of water out of the collecting duct is affected by antidiuretic hormone (ADH) and medullary ion concentration

Collecting Tubule

• Performs controlled resorption of Na+ and performs excretion of K+
• Low blood pH and volume lead to increased reabsorption of Na+ and water
• Reabsorption and secretion are regulated by hormones

Aldosterone

• This hormone is a mineral-corticoid secreted by the adrenal cortex zona glomerulosa
• Acts on the DCT and CT to promote K+ excretion and Na+ conservation
• The mineralcorticoid promotes water conservation, an increase in blood volume, and increased blood pressure

ADH

• ADH is made in the hypothalamus and stored in the posterior pituitary
• It is released into the blood
• The collecting tubules in the kidney are its target
• This hormone increases the number of aquaporins (water channels) in cells of the collecting duct
• More aquaporins mean greater water permeability of collecting tubule (CT) cells, less water in urine, and more water conserved in the blood

Stimulation of ADH Secretion

• Water deprivation
• Decrease in blood volume and blood pressure
• Increase in blood osmotic pressure
• High environmental temperature
• Overall, ADH is secreted when the body must conserve water

ADH Imbalances

• Normal urine production is 1-1.4 liters/day
• No ADH results in diabetes insipidus, excess urine output which is 40-50 liters a day
• Excess ADH can cause water retention, edema, high blood volume, and high blood pressure

Renal Clearance

• This measures glomerular filtration rate (GFR) and reabsorption
• Clearance values for glucose should be 0, meaning that all glucose is reabsorbed back into the blood
• Clearance value for inulin (which is neither reabsorbed nor secreted) at a concentration of 1 mg/ml is 125 ml/min, equal to the GFR
• Substance reabsorption increases and substance secretion decreases when the clearance rate is lower than that of inulin

Tubular Secretion of PCT and Nephron Loop

• This process removes waste, including urea, uric acid, bile salts, ammonia, catecholamines, and many drugs
• Affects acid base balance, regulating pH of body fluids via secretion of hydrogen and bicarbonate ions
• The primary function of the nephron loop is water conservation
• The nephron loop generates a salinity gradient, allows the collecting duct to concentrate urine, and is also involved in electrolyte reabsorption

Aldosterone Effects on the DCT and Collecting Duct

• Decreased blood pressure leads to renin release and the formation of angiotensin II
• Angiotensin II stimulates the adrenal cortex to secrete aldosterone
• The secretion of aldosterone promotes Na+ and water reabsorption, decreasing urine volume and maintaining blood pressure
• Steroidal hormones bind to receptors within the cell nucleus, activating transcription of the gene for the Na-K pump
• These steroid hormones require 10-30 minutes for the creation of new transmembrane pump enzymes, with noticeable effects within 30 minutes

Effect of Antidiuretic Hormone (ADH)

• Dehydration stimulates the hypothalamus, which stimulates the posterior pituitary, which releases ADH
• ADH increases water reabsorption and decreases urine volume

Atrial Natriuretic Peptide (ANP)

• The atria secrete ANP in response to increased blood pressure
• ANP dilates the afferent arteriole while constricting the efferent arteriole, increasing GFR
• It inhibits the renin/angiotensin/aldosterone pathway, ADH secretion, and NaCl reabsorption while promoting Na+ and water excretion
• ANP increases urine volume and decreases blood volume and blood pressure

Composition and Properties of Urine

• Urine appearance ranges from almost colorless to deep amber
• There is a yellow color because of urochrome, which comes from the breakdown of hemoglobin (RBCs)
• Odor causes bacteria degrade urea to ammonia
• Urine specific gravity ranges from 1.001 to 1.028
• Osmolarity in the blood is 300 mOsm/L
• The range of the osmolarity in dehydrated people is 50 mOsm/L to 1,200 mOsm/L
• The urine's pH range is from 4.5 to 8.2, usually 6.0
• Chemical composition is 95% water and 5% solutes, including urea, NaCl, KCl, creatinine, and uric acid

Urinary Bladder

• The bladder stores urine and has transitional epithelium
• The urethral sphincters are internal (smooth muscle) and external (striated muscle)
• Stretch receptors in the bladder are stimulated by about 300 ml of urine
• Micturition reflex occurs with bladder wall contraction, the relaxation of the internal and voluntary external sphincter

Complications

• Renal calculi are kidney stones that can block ureters; they are highly alkaline, concentrated, and high in calcium content and uric acids
• Other complications include cystitis (urinary bladder inflammation), glomerular-nephritis, enlarged prostate, polycystic kidney disease, and renal failure

Clinical Aspects Cont.

• Diabetes insipidus
• Diabetes mellitus