17 - Urin: Glomerular Filtration and Tubular Function

How much of the body's circulation goes directly to the kidney?

~20-25% of the body's circulation

How much liters of filtrate does the kidney make per day compared to the amount of liters of urine the kidneys make per day?

~180L of filtrate is produced

only ~1-2L of urine is produced, meaning that most of the filtrate is reabsorbed

What molecules should not be found within urine?

Protein (suggestive of damaged kidneys), glucose (suggestive of diabetes), or bicarbonate

What is the role of the renal corpuscle of a nephron?

Where blood and its dissolved components are filtered

What are the two main parts of a nephron?

Renal corpuscle - performs filtration

Tubules - performs reabsorption and secretion

where renal filtrate is modified by tubular cell absorption and secretion

What is the role of the tubules of a nephron?

Where renal filtrate is modified by tubular cell absorption and secretion

What are the two parts of the renal corpuscle?

Glomerular capsule - captures filtrate from glomerulus

Glomerulus - consists of afferent and efferent arteries that provide nutrient-rich blood to the kidneys for filtration. Consists of fenestrated capillaries which allows blood to be filtered

What are the 3 parts of a tubule of a nephron?

1. Proximal convoluted tubule

2. Nephron loop (consists of a descending and ascending limb)

3. Distal convoluted tubule

What is the role of the peritubular capillaries?

Located after the efferent arterioles of the renal corpuscle, performs reabsorption and secretion of molecules to and from the blood and the renal tubule before it returns to venous circulation

Describe the path that filtrate/urine travels through in a nephron

1. Filtrated from the afferent arteriole by the renal corpuscle

2. Travels to the renal tubule, where reabsorption and secretion occurs from the peritubular capillaries, becomes urine

3. Collecting duct, urine is collected and concentrated

4. Urine exits the nephron and travels to the renal calyces, ureter, and eventually the bladder

Where is the parietal and visceral layer located in the nephron?

Parietal layer - lines the glomerular capsule

Visceral layer - lines the capillaries of the glomerulus

Where is the capsular space of a nephron located? What is the role of the capsular space?

Located in between the visceral and parietal layer of a nephron, where filtrate that is captured by the glomerulus is collected

What is the role of the 3 cell types of the juxtaglomerular apparatus of a nephron?

Helps regulate the function of the glomerulus

Consists of

-Macula densa -> lines the distal convoluted tubule and secrets adenosine, which constricts the afferent arteriole if too much filtrate is being made in the kidneys

-Granular cells -> lines the afferent arteriole of the nephron, releases renin as part of the RAA pathway

-Mesangial cells -> relaxes the filtration slits of the glomerulus to produce more filtrate

What autonomic NS innervates the afferent arteriole of a nephron? What is the significance of this?

Sympathetic Nervous System

Can constrict the afferent arteriole to reduce urine output of the nephron (because you dont want to piss when youre running from danger)

What are the 3 components of the filtration membrane of the glomerulus?

1. Fenestrated endothelial cells on the capillaries (allows large objects to pass through)

2. Basal lamina (repels smaller protein)

3. Filtration silts (from the pedicel of podocytes)

What is the role of the fenestrated endothelial cells in the nephron?

Allows larger molecules to be filtered by the filtration membrane, such as water, ions, and small molecules, while preventing large proteins and rbcs from passing through

Helps the nephron work on a size exclusion principle

What is the role of the basal lamina in the nephron?

Negatively charged, works to repel smaller proteins from being filtered by the filtration membrane

What is the role of filtration silts in the nephron?

Helps regulate glomerular filtration rate of the nephron. Can form larger silts to decrease water retention, or form smaller silts to increase water retention

What force drives filtration into the renal corpuscle?

High capillary hydrostatic pressure

What two forces opposes filtration into the renal corpuscle?

Blood oncotic pressure and capsular hydrostatic pressure

What two intrinsic mechanisms of the kidney can be used to alter glomerular filtration rate? What are these mechanisms called?

Autoregulation of GFR

1. Myogenic mechanism - reflex of smooth muscles

2. Tubuloglomerular feedback - adenosine release

What 4 mechanisms help regulate glomerular filtration rate?

1. Myogenic Mechanism (increase bp =afferent arteriole to normal GFR)

2. Tubuloglomerular feedback (high filtrate = afferent arteriole to decrease GFR)

3. Angiotensin II (decrease bp = increase bp + afferent arteriole to decrease GFR)

4. Atrial natriuretic peptide (heart distention = filtration silts to increase GFR)

What is the myogenic mechanism of regulating glomerular filtration rate?

Helps return GFR rate back to normal in response to high bp

High bp causes smooth muscle of afferent arterioles to stretch which initially increases GFR, however, the smooth muscle begins to contract as a reflex once it is stretched back to its normal size, which causes GFR to return back to normal

What is the tubuloglomerular feedback mechanism of regulating glomerular filtration rate?

Helps decrease filtration production in repone to high amounts of filtration flow

Receptors on the macula densa cells detect high concentration of Na+, which results in the release of adenosine that causes constriction to the afferent arteriole, which reduces glomerular filtration rate)

How does angiotensin II regulate glomerular filtration rate?

Decreases glomerular filtration rate by contracting all arterioles in response to low blood pressure

The granular cells of the juxtaglomerular apparatus of the kidneys detects a decrease in blood pressure or SNS stimulation, which causes a release of renin and eventually the creation of angiotensin II.

Angiotensin II causes vasoconstriction of both systemic and glomerular afferent arterioles.

Vasoconstriction of systemic arterioles increases blood pressure

Vasoconstriction of afferent arterioles decreases GFR

How does atrial natriuretic peptide regulate glomerular filtration rate?

Increases glomerular filtration rate in response to heart distension by spreading out filtration slits

Distention of the heart due to increased blood volume causes ANP to be released from the heart. ANP then acts on mesangial cells of the juxtaglomerular apparatus of the kidney, which causes filtration slits on the filtration membrane to widen, allowing more filtrate to be produced

This causes blood volume to be lowered, causing the heart to not be distended anymore.

What molecules are completely reabsorbed by the kidney?

Glucose ~162g in filtrate but completely reabsorbed

Protein/amino acids ~2.0g in filtrate, with 0.1g being excreted by urine

Bicarbonate ions

What molecules are regulated and thus partially absorbed by the kidney?

Water ~180L in filtrate, with 1-2L being excreted by urine

Sodium ~570g in filtrate, with 4g being excreted by urine

Potassium

Chloride

What molecules are excreted as waste products by the kidney?

Uric acid ~8.5g in filtrate, with 0.8g being excreted in urine

Creatinine -1.6g in filtrate, with 1.6g being excreted in urine

Drugs

Drug metabolites

Other nitrogenous wastes

What force drives the movement of water?

Osmosis, a passive mechanism in which water follows its concentration gradient through a semipermeable membrane towards a lower concentration of water or high concentration of solutes

What is obligatory water reabsorption? How much water is reabsorbed through this mechanism?

Water that is dragged along by solutes being moved from the tubules to the interstitial fluid, happens without any regulatory mechanisms

About 90% of water reabsorption is obligatory

What is facultative water reabsorption? How much water is reabsorbed through this mechanism?

Water reabsorption that can increase or decrease depending on the needs of the body, occurs through hormone regulation to maintain homeostasis within the body

Where does most obligatory water reabsorption take place within the kidney?

Occurs within the proximal convoluted tubule and the nephron loop as these areas have tubules that are permeable to water

Where does most facultative water reabsorption take place within the kidney?

Occurs within the collecting ducts that are permeable to water due to influence of antidiuretic hormone

Where does most reabsorption of organic solutes occur within the kidney?

Mostly occurs in the proximal convoluted tubule, including the reabsorption of around 65% of water

What is passive transport? What are the various routes of passive transport through the tubules?

Movement of solutes without using any additional energy

1. Paracellular route - diffusion through the tight junction of cells

2. Transcellular route - diffusion through the cells of the tubules through facilitated transport using transport proteins, or leakage channels

What is active transport? What are the various forms of active transport through the tubules?

Movement of solutes with additional energy

1. Primary active transport - use of only ATP to transport molecules

2. Secondary active transport - coupling of movement of solutes with the movement of ions down their concentration gradient with the use of energy (cotransporters)

What are the various forms of secondary active transport?

1. Transport protein/ions and solutes move in same direction = symporter

2. Transport protein/ions and solutes move in opposite direction = antiporter

Both molecules are called cotransporters

What is the paracellular route of sodium reabsorption to the peritubular capillaries?

Apical Membrane

Sodium moves from high concentration in the tubules to low concentration in the peritubular capillaries through the tight junction between tubule cells (passive transportation)

What is the transcellular route of sodium reabsorption to the peritubular capillaries?

Apical membrane

Sodium leak channels allows sodium to move from high to low concentration into the tubule cells (passive transportation)

Basolateral membrane

Na+/K+ ATPase shuttles 3 Na+ ions into the peritubular capillary and expels 2 K+ ions with the use of ATP (active transportation)

How does glucose reabsorption occur from the tubules to the peritubular capillaries?

Apical membrane

1 glucose molecules is transported into the cell by shuttling 2 Na+ ions into the cell as well, moving from high to low concentration. (symporter)

The low sodium concentration gradient in the tubule cell is maintained by Na+/K+ ATPase, which shuttles 3 Na+ ions into the peritubular capillaries and 2 K+ ions into the tubule cell using ATP (secondary active transport)

Basolateral membrane

The glucose travels through a protein channel to diffuse to the peritubular capillary, from high to low concentration (passive transport)

How does H+ secretion occur from the peritubular capillaries to the tubules?

The bicarbonate buffer system occurs within the tubule cell, using CO2 and H2O from the peritubular capillary and the tubules. This results in carbonic acid being produced, which dissociates into H+ and HCO3-

Hydrogen (H+) is shuttled back into the tubules through an antiporter that allows sodium into the tubule cell in exchange. In order to maintain a low concentration of sodium in the tubule cell, 3 Na+ is shuttled out of the tubule cell with 2 K+ ions being shuttled into the cell via Na/K+ase (secondary active transport)

This excretion of H+ results in overall blood pH becoming more basic (higher)

How does HCO3 generation occur in the tubule cells?

The bicarbonate buffer system occurs within the tubule cell, using CO2 and H2O from the peritubular capillary and the tubules. This results in carbonic acid being produced, which dissociates into H+ and HCO3-

Bicarbonate (HCO3-) is shuttled back into the cell through facilitated diffusion using a protein channel, which allows bicarbonate to travel from high concentration, to low concentration into the peritubular capillary (passive transport)

This generation of HCO3 increases the buffer capacity of blood, as more H+ can bind to HCO3

Why is the apical membrane impermeable to water in the ascending nephron loop?

Consists of thick tight junctions between the tubule cells, which prevents osmosis from occuring

How does chloride reabsorption occur from the tubules to the peritubular capillaries?

Apical membrane

2 Chloride, 1 sodium, and 1 potassium ion travels through a symporter into the tubule cell from high to low concentration.

The low potassium concentration is maintained by K+ leak channels on the tubular cell membrane, which allows K+ to move out of the tubule cell to the tubules.

The low sodium concentration is maintained by Na+/K+ ATPase, which shuttles 3 Na+ ions out of the cell for every 2 K+ ions into the cell via ATP (secondary active transport)

Basolateral membrane

The chloride diffuses through a leak channel from high to low concentration to reach the peritubular capillary (passive transport)

How does paracellular cation reabsorption occur from the tubules to the peritubular capillaries? Which ions travel through this pathway

Apical membrane

Magnesium, sodium, calcium, and potassium diffuse through the thick tight junction between the tubular cells from high to low concentration into the peritubular capillaries (Passive transport)