Glomerular Filtration and Tubular Function

2 Parts of the Nephron

1) Renal Corpuscle: Consists of a glomerulus which is a fenestrated capillary network that filters blood as well as a glomerular capsule which collects that filtrate.

2) Tubules: Proximal and distal convoluted tubules as well as ascending and descending nephron loops where the filtrate can be adjusted.

• Glomerular filtration (allowing small molecules to enter the tubules) occurs in the renal corpuscle.

• Tubular reabsorption and secretion occur along the renal tubule and collecting duct.

• Peritubular capillaries (the glomerular blood vessel) extends and stretches around the tubules to allow for reabsorption and secretion

Structure of the Renal Corpuscle (Layers, cells, neurons)

• The glomerular capsule is covered by a parietal layer which then becomes continuous with the visceral layer covering the glomerulus. 

• The glomerulus is covered by a visceral layer of modified epithelial cells (podocytes).

• Between these two structures lies the capsular space where filtrate is collected.

• The proximal convoluted tubule is lined with cuboidal epithelial cells.

• A sympathetic neuron is on the afferent arteriole to send signals during flight or fright response and blood loss to constrict arteriole

3 Cells of the Juxtaglomerular Apparatus

• The juxtaglomerular apparatus lies next to the glomerulus and helps regulate its function. It contains 3 important cells

1) Macula Densa Cells: Release adenosine to make the afferent arteriole constrict to limit fluid loss (Hint: Densa and denosine sound similar)

2) Granular Cells: Release renin as part of the RAA pathway (Hint: Granular ends in R and renin starts with R)

3) Mesangial Cells: Open the filtration slits to make the kidneys lose a lot of water (Hint: Mesiahs usually have open arms)

3 Components of the Filtration Membrane of the Glomerulus

• 1) Fenestrated endothelial cells/capillary wall: Allow small molecules to enter the filtrate

• 2) Negatively charged basal lamina: Negatively charged collagen fibers that repel negative proteins to prevent them from entering the filtrate.

• 3) Podocytes: Contain foot-like processes called pedicels that make the filtration slits which can have wider or smaller gaps to control how much water and filtrate leaves. Works on a size exclusion principle

• High capillary hydrostatic pressure drives filtration while blood oncotic pressure and capsular hydrostatic pressure opposes filtration

What is Autoregulation

• The kidney itself can act to alter the GFR. We call this autoregulation because the mechanisms are intrinsic to the kidney.

• The filtration rate is easily altered by changing the blood pressure in the glomerulus, or the leakiness of the capillaries (size of filtration slits).

2 Ways to Alter Glomerular BP

• 1)Myogenic mechanism: The smooth muscle of the afferent arteriole is stretched by the increased BP which changes the GFR.  The afferent arteriole responds with constriction which reduces GFR.

• 2) Tubuloglomerular Feedback: The macula densa of the juxtaglomerular apparatus detects high amounts of NaCl in the filtrate. It responds by increasing adenosine, which constricts the afferent arteriole to decrease the amount of NaCl coming in and decreases GFR.

2 Hormones that Regulate GFR and How

• 1) Ang II: Made by liver. Ang II decreases GFR because it constricts the afferent arterioles but increases BP because it also constricts systemic arterioles. A decrease in BP or an increase in sympathetic nervous stimulation (fight or flight) will talk to the juxtaglomerular apparatus (specifically granular cells) which will release renin which will release Ang I and Ang II which will constrict systemic and glomerular afferent arterioles which will increase BP.

• 2) ANP: Increase GFR. Distension of the heart leads to release of ANP. ANP causes relaxation of the mesangial cells between the glomerular capillaries. This increases the filtration slits and relaxes glomerular capillaries. Once the blood volume goes down, the pressure in the heart decreases, and ANP is no longer secreted.

What is gained and lost within a day (water, glucose, protein, sodium, uric acid, creatinine)

• There is a lot of stuff within the filtrate. Some of it in the tubules gets completely reabsorbed (glucose, amino acids, bicarb), some of it is regulated and thus partially reabsorbed (water, electrolytes), and some of it is completely excreted as waste (urea, creatinine, drugs)

  • Water is heavily reabsorbed but not reabsorbed completely

  • Glucose is completely reabsorbed

  • Protein is mostly reabsorbed but some is left in the urine

  • Sodium is mostly reabsorbed

  • Uric Acid is mostly reabsorbed

  • Creatinine is complete excreted

Obligatory vs Facultative Water Reabsorption

• About 90% of tubule water reabsorption is obligatory (it has to happen due to the movement of solutes outside the tubule.)

• About 10% of water reabsorption is facultative, meaning it can increase or decrease depending on the body's needs.

• Much of the obligatory reabsorption of water will occur in the proximal convoluted tubule and the nephron loop because these areas are permeable to water.

• Facultative water reabsorption is under the control of ADH which makes the cells in the collecting duct permeable to water.

Osmosis

• Movement of water will all be by osmosis.

• The most active area for reabsorption is the proximal convoluted tubule. By the end of the PCT, 100% of most organic solutes have been reabsorbed because the movement of water through osmosis attracts it.

• 65% of the water has also been reabsorbed

Passive Transport: Paracellular vs Trasncellular

• Some solutes can slip between the tight junctions of the cell (paracellular) or through cells (transcellular) strictly by following the EC gradients. Facilitated diffusion channels (for things like glucose) and leakage channels also exist to help ions move.

Active Transport (symporters and antiporters)

Primary and secondary active transport move other substances in or out of the filtrate (a symporter is a secondary active transport protein that moves solutes in the same direction it is going. An antiporter moves the solute in the opposite direction. Both are co-transporters.). In the PCT, active transport is done via the Na/K ATPase in the transcellular basolateral membrane.

Secondary Active Transport of Glucose

• The reabsorption of glucose from the filtrate occurs via secondary active transport in the PCT.

• A 2Na glucose symporter allows glucose to cross the apical membrane via 2ndary active transport while a facilitated diffusion transporter allows it to cross the basolateral membrane into the blood.

• The actions of the sodium potassium ensure the conc grad for sodium is maintained.

Na/H+ Antiporter

• CO2 from the blood enters the PCT cells, where it combines with water to form HCO3 + H. The H is kicked out into the lumen and a Na from the lumen is brought in through the Na/H antiporter. The Na is kicked out to the blood through the pump. HCO3 is put into the blood to maintain buffering capacity.