Normally, Urine produced by healthy kidneys is a cocktail of toxic waste products of cellular metabolism, a host of minerals, salts, smelly organic compounds & excess water. (Find the complete normal urine composition here). These components begin to get together to form Urine once healthy kidney micro-filters “strain” our blood through themselves. These micro-filters are uber-selective with what they “let-out” into the urine. This is such that, all blood cells & “plasma” proteins remain in the bloodstream while the wastes & excesses purge themselves out.
But what makes these Kidney Micro-filters that selective against leakage of blood cells & protein in urine?
LET’S DISSECT!
Normally, when blood loaded with toxic wastes reaches the kidneys for filtration, it enters the kidneys through one of the large pipelines called the “Renal Artery”. Once within the kidney, the blood gets distributed via numerous tiny branches of blood vessels to individually reach out to each one of the 1-1.5 million individual Nephrons (“filtration units”) in each kidney for efficient filtration. That’s just one of the ways how Mother Nature applies “Division of Labour” within our body!
Now, blood vessels reach each nephron and form an entangled, scrunched-up loop to “sit on the cup-like head of the nephron” (Image A below). The technical name for this entangled loop of blood vessels is “Glomerulus” (glom-er-you-lus). Remember this name! Because this is where all the barrier action against leakage of proteins in Urine takes place.
The Glomerulus is a beautifully intricate piece of work by Mother Nature. This portion of blood vessels in healthy kidneys has a special lining of a 3-layered filtration system to cater to the ultra-selective nature of kidney filters.
The layered arrangement serves as a “Filtration Barrier” for both blood cells and plasma proteins. These are present in each of the million-plus nephrons in healthy kidneys. Refer to Image B and the explanation that follows below to understand the barrier function.
The blood that enters the kidney gets distributed to each Glomerulus in a nephron for filtration. At the point of entry to the nephron, it encounters the following “blood-cell blocking” &”protein-selective” layers from inside-outwards:
LAYER 1:
This layer is called the Glomerular “Endo-thelium” or quite literally, “the inner lining”. It is made of specialized cells that are arranged in a manner such that there are tiny, uniformly-sized “pores” between them. These pores are big enough to let-out all cellular waste products in the blood as well as most of the Plasma proteins up to the next layer. But each of these pores is about 75% smaller than an average red blood cell. As a result, this layer effectively blocks blood from leaking into the Urine.
LAYER 2:
The layer forms a “base” for the 1st layer described above. So, quite aptly, Scientists call it the Basement Membrane. This layer has pores in it as well. However, these pores are much smaller than those in Layer 1 such that, it prevents all Large Plasma Proteins from getting through. However, all the waste products and Medium-sized & Tiny Proteins still make their way to Layer 3.
LAYER 3:
Moving on to this layer, it’s time to acknowledge Nature’s pure Artistry!
Layer 3 is the “Epi-thelium” that literally means “the outer layer”. Normally all surfaces in our organs have “epithelial cell-layers” as protective covers. These layers consist of cells which are either column-like or rectangular mattress-like in shape. But keeping in mind the Filtration function of kidneys, Nature converted the epithelial cells in Layer 3 into disc-shaped bodies with multiple finger-like structures (called the “Foot Processes”) emerging from them. Physiologists have named these cells Podocytes (pronunciation: podo-sites) meaning “cells with feet”.
As Image B depicts, the arrangement of each Podocyte in Layer 3 is such that the foot processes from adjacent podocytes mutually intertwine. This is somewhat like how fingers lock when holding hands. This arrangement creates tiny slit-like spaces between the foot processes in Layer 3 that effectively stop almost all Plasma Proteins (except for very few tiny proteins) from finally leaking into the Urine within the nephron tube. Importantly, this layer does not block the waste product traffic in the blood from passing through. So, the Podocyte Layer is in charge of the “Final Protein Policing” in kidneys.
Therefore, the innermost layer in the Glomerulus i.e. Layer 1 (shown in yellow) efficiently prevents red blood cells from crossing over to form urine. In other words, Layer 1 prevents “Glomerular Haematuria”.
NOTE: Glomerular Haematuria or red blood cells crossing over to get into Urine is just one of the ways that a patient may present with blood in the urine. However, when present, it usually indicates Kidney Disease that warrants a thorough medical check-up. There are other reasons for bleeding in urine as well that do not directly relate to Kidney malfunction.
On the other hand, all three filtration layers of the Glomerulus (Layers 1-3) act in tandem to bar Plasma Proteins (eg: Albumin) from leaking in your Urine.
It is Nature’s tactful arrangement of progressively reducing pore sizes across filtration layers & their tight-knit geometry that guards against “Glomerular Proteinuria” — the hallmark of Kidney Disease.
IN ADDITION:
Apart from the size of pores in the three-layer filtration system of the Glomerulus in the kidney filters, there is a concept of “Chemical Charge”, that governs what filters through the pores and what doesn’t.
Let us explain.
All living surfaces have an overall positive or negative charge on them. This comes from the various chemical molecules that comprise the particular surface in question. It’s no different when it comes to filtration cells in kidneys, biomolecules such as plasma proteins and blood cells. It is this chemical charge present on Kidney Filtration Cells, Blood cells & plasma proteins (such as Albumin) that helps with the protein & blood-cell barrier action.
Two surfaces that have a similar charge (i.e. both negative or both positive) tend to move away from each other.
Normally, cells lining the 3 filtration layers of the glomerulus, the blood cells & plasma proteins are ALL negatively charged. This means the Kidney Filters literally repel a major chunk of Plasma Proteins & all Blood cells from getting too close to their pores in the first place! And even if they do get close to each other, you have the intelligently sized pores to prevent these from leaking out.
This delicate “pore-size & charge-based barrier action” is vulnerable to get compromised if there is something that’s constantly shoving, pushing-through & damaging the filtration layers in the Glomerulus over a period of time. As a consequence, either protein or both protein & red blood cells may start leaking into the Urine.
IN A NUTSHELL:
BLOOD CELL LEAKAGE
- The chemical charge & size of Pores in the innermost Layer (Glomerular endothelium or Layer 1 in the image above) of the Glomerulus prevents Blood leakage in Urine in normal health.
- Damage to Layer 1 will cause leakage of Blood Cells in Urine.
- Prolonged sustained High Blood Pressure & some diseases of the Immune System (IgA Nephropathy). can damage Layer 1.
PROTEIN LEAKAGE
- Specialized cells called Podocytes clad the outermost layer (Layer 3) of the glomerulus in healthy kidneys. These ensure that the initial filtrate remains free of any blood cells & almost all plasma proteins.
- Tiny proteins that do occasionally make their way into the filtrate are absorbed back into the bloodstream.
- Even minor damage to Layer 3 would be enough for medium-sized proteins such as Albumin to leak into the Urine.
Commonest reasons for progressive damage to these layers include:
- Prolonged sustained high blood pressure
- Uncontrolled high blood glucose (as in Diabetes mellitus)
- Immune system diseases affecting kidneys including but not limited to Minimal change disease, IgA Nephropathy, FSGS, Lupus Nephritis, Nephrotic Syndrome
- Also, when kidneys fail to re-absorb the tiny proteins passing into the initial filtrate, Urine may test positive for protein.
A simple Urine Routine Test (Urinalysis) is enough to find out if you are leaking protein, blood or both in Urine or not.
If you test positive for either or both, seek an urgent medical appointment to get your kidneys checked.
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