# Glomerular Filtration --- **Glomerular filtration** is the first step of the blood filtration process that takes place in the [[kidneys]] (specifically the renal corpuscle of a [[nephron]]) where the filtrate is separated from the blood. - **Step 1**: The blood enters the [[glomerulus]] through the afferent arteriole. - **Step 2**: The filtration pressure forces almost everything out of the blood, including the [[plasma]] and most small molecule through the [[glomerulus#Filtration Membrane|filtration membrane]]. This substance enters the [[nephron#Renal Tubule|renal tubule]] where it is now referred to as **filtrate**. - **Step 3**: The rest of the blood (which is essentially only blood cells and large molecules) leaves from the efferent arteriole. - **Step 4**: What the blood wants to keep it will take back during [[tubular reabsorption]]. ## Glomerular Filtration Rate & Net Filtration Pressure The **glomerular filtration rate** or **GFR** is the rate at which filtrate is formed. It is dependent on the **net filtration pressure**, or **NFP**. If the NFP drops too low, the kidneys have a hard time filtering the blood. It takes 24 hours to accurately measure GFR (see [[#Measuring GFR|below]]) so we will often see an an estimated GFR or **eGFR**, which estimated using some complex algorithm and a spot creatinine check. >[!science] Normal Values The normal GFR for someone who has healthy kidneys is >90 mL/hr. In the hospital setting the cutoff for kidney disease is usually 60 mL/hr > ![[eGFR.png]] NFP is dependent on three factors, the [[hydrostatic pressure]] of the blood, colloid [[osmosis|osmotic pressure]] and hydrostatic pressure from the filtrate already in the glomerular space. The blood hydrostatic pressure is largely dependent on the overall [[blood pressure]], but can be finely tuned by the diameter of the afferent and efferent [[glomerulus|arterioles]]. Colloid osmotic pressure is driven by the fact that plasma proteins are the strongest factor of determining osmotic pressure, and they are too large to fit through the filtration membrane, thus they stay inside the blood. Combining all these factors, we can calculate net filtration pressure in the glomerulus as: $ HP_g - (OP_g + HP_c) = NFP $ ![[GFR.png]] ### GFR Regulation Regulating the GFR is essential for healthy kidney functions. **The normal GFR is roughly 120-125 ml/min**. - if GFR is too **slow**, the substances that need to be excreted end up getting reabsorbed, because it takes too long to get through the tubules. - if GFR is too **fast**, the substances that need to be reabsorbed end up getting excreted because there's not enough time in the tubules. >[!science] Normal GFR Normal GFR varies between **125 mL/min** to **200 mL/min** There are two real factors that the system corrects for: **changes in blood pressure** and **changes in blood osmolarity**. High blood pressure can be really damaging to the kidneys, and low blood pressure will not filter the blood at a good rate. Osmolarity can also affect GFR by changing the blood osmotic pressure, but also indicates a low blood volume. >[!health]- Detailed GFR regulation > ![[GFR regulation.png]] #### Intrinsic Controls The **intrinsic controls**, or **renal autoregulation** are the ways in which the kidney itself can regulate the GFR. These are able to respond quickly to some fluctuation in blood pressure and osmolarity. This is actually happening *all the time*. There are two mechanisms of intrinsic control are the **myogenic response** and the **tubuloglomerular feedback mechanism**. They both work by altering the diameter of the [[glomerulus|afferent arteriole]] (where blood enters the glomerulus). Recall that the afferent arteriole is generally larger than the [[glomerulus|efferent arteriole]] (where blood leaves the glomerulus), which helps it build up a high local pressure gradient. This is like the valve on a hose faucet. The more dilated the afferent arteriole, the more fluid can get in, the more fluid enters into the glomerulus, the higher the GFR. The efferent arteriole can also affect GFR by dilating and contracting, but generally this has much less influence on the the afferent arteriole. - The **myogenic response** is when the afferent arteriole constricts in response to a rise in systemic [[blood pressure]], so that less blood can enter the glomerulus. - The **tubuloglomerular feedback mechanism** is when the macula densa cells of the [[glomerulus#The Juxtaglomerular Apparatus|juxtaglomerular apparatus]] sense an increase in tubular NaCl concentration, and signal the afferent arteriole to contract, we well as [[cell signaling|signaling]] the [[glomerulus#The Juxtaglomerular Apparatus|mesangial cells]] to contract, both of which decreases GFR. #### Extrinsic Controls The **extrinsic controls** of maintaining a healthy GFR are slower than the intrinsic controls, but can compensate for larger fluctuations in blood pressure. These can be **neural** or **hormonal**. - The **neural controls** are the activation of the [[sympathetic nervous system]], which triggers vasoconstriction of the afferent arteriole and the [[glomerulus|mesangial cells]] of the glomerulus. - The **hormonal controls** consist of releasing [[renin-angiotensin-aldosterone system|renin]], [[antidiuretic hormone|ADH]] and [[renin-angiotensin-aldosterone system|aldosterone]] if the blood pressure is too low, and releasing [[atrial natriuretic peptide|ANP]] from the heart of it's too high. ## Measuring GFR We can measure GFR indirectly by measuring the kidney's clearance of [[creatinine]]. Since it's a waste product and there is no reason to reabsorb creatinine, measuring it's clearance is a good way of measuring how much blood moves through the glomeruli. To find this out we take a 24-hour urine collection and measure creatinine right in the middle. We can then use this formula to determine GFR: volume of urine X urine creatinine `over` serum creatinine ___