Renal Anatomy and Glomerular Function

Hi :) In this post we'll begin the next topic in our first Veterinary Physiology unit - the Renal System. Today we'll have a look at the anatomy of the renal system, how angiotensin 2 is produced and the Starling forces which function in the glomerular capillaries. We'll also go over a few key definitions as well as the importance of resistance in the renal system and the mechanisms which regulate glomerular filtration rate.

The Anatomy of the Renal System

The renal system contains the kidneys which are linked to the bladder by ureters. The contents of the body exit via the urethra. The bladder stores urine which is made by the kidneys. The kidneys contain nephrons, the functional unit of the kidney. Nephrons are composed of two main sections:

• The Renal Corpuscle, which consists of:
• the glomerulus: this is the tuft of capillaries where blood is filtered. 
• the Bowman's capsule: This is where the filtrate collects. 
• The Renal Tubule: this collects the filtrate from the Bowman's capsule and modifies its composition by exchange with interstitial fluid. Filtrate passes from here into the collecting duct. The collecting duct then leads to the ureter which leads to the bladder and eventually exits the body via the urethra.

There are two categories of nephrons:

1. Cortical Nephrons: These nephrons lie predominately in the renal cortex
2. Juxtamedullary Nephrons: In these nephrons, the loop of Henle travels deep into the renal medulla. This assists in maintaining an osmotic gradient and helps to concentrate the urine. 

The more juxtamedullary nephrons an animal has, the more concentrated their urine will be. This is because as the loop of Henle goes deeper into the medulla the osmotic gradient becomes larger which allows the urine to become more concentrated. This allows the animal to save water. 

Mammalian and Avian Renal Structure

Birds have two types of nephrons in their kidneys: reptilian-type nephrons and mammalian-type nephrons. Reptilian-type nephrons have no loop of Henle and so cannot concentrate urine as well as mammalian-type nephrons. Mammalian-type nephrons are those which were described earlier. Sometimes, a bird may ingest a lot of salt and will thus need to conserve water. When this happens filtration in the reptilian-type nephrons stops and mammalian-type nephrons function instead. This allows the bird to conserve water.

The Juxtaglomerular Apparatus 

The juxtaglomerular apparatus (JG apparatus) is a modified group of cells that assist in regulating blood volume and pressure. They are located where the late ascending loop of Henle and the early distal convoluted tubule come into contact with the cells of the afferent arteriole. It contains two groups of cells: the macula densa and the granular cells. The macula densa are chemoreceptors which respond to changes in NaCl concentration in the filtrate. Granular Cells are mechanoreceptors and detect changes in blood pressure. They are also smooth muscle cells that have secretory granules which contain renin.

Some Key Definitions

Before we continue, there are a few definitions that are worth knowing:

• Glomerular Filtration Rate (GFR): this is the volume of blood plasma which is filtered through both kidneys per unit of time per kilogram of body weight. GFR is determined by:
• net glomerular filtration pressure (GFP)
• permeability of filtration barrier
• and the surface area available for filtration.
• Filtration Fraction: this is the fraction of the renal plasma that is entering the afferent arteriole that is filtered at the glomerulus.
• Filtered Load: this is the quantity of a particular solute, filtered per unit time. The filtered load increases when the GFR increases or the plasma solute concentration increases. 

Starling Forces

Filtration at the glomerulus is driven by Starling forces (see this post). This includes:

• Hydrostatic Pressure: this is the pressure exerted by water as it moves from places of high to low hydrostatic pressure. 
• Glomerular Capillary Hydrostatic Pressure (PGC):This favours filtration from the glomerulus. It is higher than normal blood pressure because the resistance in the efferent arteriole causes pressure to build upstream. This is equal to 60mmHg. 
• Bowman's Capsule hydrostatic pressure (PBC): This opposes filtration from the glomerulus. It equals 15 mmHg.
• Thus, the net hydrostatic pressure gradient favours filtration at the glomerulus. 
• Oncotic Pressure: the presence of non-permeating solutes exert an osmotic pressure. This oncotic pressure is created mainly by proteins. Its effect is to draw water from areas of low protein concentration to areas of high protein concentration. 
• Glomerular Oncotic Pressure (πGC): this opposes filtration because the presence of proteins in the plasma draws fluid back to the glomerulus. This force = 30mmHg
• Bowmans' Capsule Oncotic Pressure (πBC): this provides very little osmotic force in normal individuals because proteins are not normally present in filtrate. Thus this force = 0 mmHG (in normal individuals). If it is present it will favour filtration.
• Thus, the nett oncotic pressure gradient opposes filtration at the glomerulus. 

In order to filter the blood a glomerular filtration pressure must be present and it needs to be positive. The glomerular filtration pressure (GFP) is the sum of all the Starling forces that favour filtration minus those that are opposing filtration. The glomerular oncotic pressure increases gradually due to the filtration of protein-free fluid. The Glomerular and Bowman's capsules hydrostatic pressures, however, remain relatively constant.

The glomerular capillary hydrostatic pressure is determined by the resistance in the afferent and efferent arterioles as well as the renal artery pressure. Because of this, if the afferent arteriole constricts and causes a decreased flow to the glomerulus, hydrostatic pressure and glomerular filtration rate will decrease. If this arteriole dilates, there will be an increase in the flow to the glomerulus as well as an increase in hydrostatic pressure and GFR. If the efferent arteriole constricts, fluid movement is inhibited and this increases hydrostatic pressure and GFR. If the efferent arteriole dilates fluid moves more quickly from the glomerulus and this reduces the hydrostatic pressure and GFR.

The Regulation of GFR

It is important for the kidneys to maintain a stable glomerular filtration rate. The kidneys can achieve this through three main ways:

1. Myogenic Regulation: This is considered part of renal autoregulation. It involves the regulation of smooth muscle in the afferent arteriole which alters resistance to blood flow and maintains GFR. If the mean arterial pressure (MAP) increases the afferent arteriole constricts to prevent an increase in glomerular hydrostatic pressure and GFR. If the MAP decreases, the afferent arteriole dilates to prevent a reduction in PGC and GFR.
2. Tubuloglomerular Feedback: This is also considered part of autoregulation and is the alteration of arteriolar tone in response to sodium chloride concentrations in tubular fluid (which is dependent on tubular flow rate). An increased flow and GFR past the macula densa increases the delivery of NaCl. This causes the macula densa to release a chemical which causes arteriolar vasoconstriction which offsets the initial elevation of MAP and this maintains GFR. On the other hand, a decreased GFR and NaCl delivery causes vasodilation.
3. Sympathetic Nervous System: When MAP drops below 80mmHg or rises above 180mmHg the sympathetic nervous system kicks in. Baroreceptors detect a drop in pressure which causes an increase in sympathetic nerve activity. This leads to vasoconstriction of the afferent arteriole which cuases a decreased GFR.
4. Renin-Angiotensin-Aldosterone System (RAAS): The aim of the RAAS is to increase blood volume and MAP. The juxtaglomerular cells of the afferent arteriole synthesise, store and release renin. Renin is released in response to a decrease in MAP or blood volume. Once renin is released it converts angiotensinogen to angiotensin 1 in the liver. This molecule in then transported to the blood plasma and is then converted to angiotensin 2. This reaction is catalysed by ACE (Angiotensin Converting Enzyme), which is located in the lungs and the brush border of the proximal renal tubule. Angiotensin 2 has several functions:
1. Arteriolar vasoconstriction: this increases resistance and raises MAP
2. Stimulates aldosterone secretion: this promotes Na+ reabsorption at the distal nephron. (Water follows Na+ so this helps to increase blood volume)
3. Directly stimulates Na+ reabsorption at the kidney: this directly increases Na+ reabsorption at the renal tubules (water follows)
4. Stimulates ADH release to activate the thirst centre: this increases water reabsorption and drinking.

It's important to note that thirst is the only effect that will actually increase blood volume directly. The other effects of angiotensin 2 just minimise water loss. 

That's all for this post, if you have any questions please feel free to ask :)