Categories
Renal Physiology

Glomerular Apparatus

mesengial cells

General Considerations

All nephrons have one glomerular apparatus each. Each glomerular apparatus is a critical contributor to the renal function. Here are the functions performed by the glomerular apparatus. Notice that the tubular secretion and reabsorption is not performed by the glomerular apparatus.

  1. Filtration of the substances. This is the first step in the urine formation. (Filtration Barrier.)
  2. Prevention of filtration for the substances that we don’t want to loose. For example blood cells and proteins. (Filtration Barrier.)
  3. Blood pressure measurement and maintenance. (Juxtaglomerular cells.)
  4. Blood osmolality measurement and maintenance. (Macule Densa cells.)
  5. Renin release to help maintain body fluid volume and blood pressure. (Macula Densa cells.)
  6. Blood flow regulation to the glomerulus to control the rate of filtration. (Mesangial cells.)

Structures forming Glomerular Apparatus

This apparatus is formed by following structures:

  1. Bowman’s capsule of a nephron.
  2. Glomerular capillaries and the basement membranes.
  3. Podocytes or the visceral layer of the bowman’s capsule.
  4. Mesangial cells inside the bowman’s capsule and immediately outside of it.
  5. Juxtaglomerular cells in the walls of the afferent and efferent arterioles.
  6. Macula Densa cells in the wall of the distal convoluted tubule of the same nephron.

Functional Considerations

Filtration

Glomerular filtration barrier is composed of endothelial cells, basement membrane and the podocytes. Podocytes are the visceral layer cells of the bowman’s capsule. Podocytes and the capillary endothelial cells share one common basement membrane that is sandwiched between them. We will discuss details about this barrier in another lecture. Here it is important to note that this barrier allows the fluids and selective substances to move from the blood compartment to the bowman’s space of the nephron.

filtration

Selective Filtration

Filtration barrier mentioned above also prevents filtration of proteins and blood cells. This is accomplished by progressively smaller fenestrations (holes) in the barrier and also be the abundance of negative charges in the barrier. As an example, albumin is about 4nm but still is not able to move out of the blood compartment because of the strong negative charges on the barrier (proteins are usually negatively charged.)

Blood Pressure measurement and Maintenance

Juxtaglomerular cells detect the stretch in the arteriolar wall due to the blood pressure and release renin if necessary. Renin in turn work with Angiotensin to help regulate blood pressure and blood volume.

JG cells

Blood osmolality measurement and maintenance

When the distal convoluted tube ascends and reaches near its corresponding bowman’s capsule the cells in its wall facing the bowman’s capsule become specialized cells. These cells are called macula densa cells. As these cells are facing the urine compartment (nephron lumen) they are able to measure the osmolality of the urine. Macula densa cells release ATP or Adenosine when the osmolality is not correct. JG cells contract or relax under the influence of this ATP and/or Adenosine. Result is blood flow regulation to the glomerulus which in turn helps regulate body fluid volume and osmolality.

macula densa

Blood flow regulation to the glomerulus by the mesangial cells

Mesangial cells are derived from the smooth muscle cells. Hence they have contractile activity in addition to the phagocytic activity. In fact these are the only phagocytosing cells that are not derived from the monocytes. It is thought that these cells can also help regulate the blood flow to the glomerulus. This effect seems less important compared to their phagocytic activity.

mesengial cells

Categories
Renal Physiology

Introduction to the Urine Formation

Urine is formed in the kidney’s nephrons by a combination of following three processes:

  • Filtration
  • Tubular Secretion
  • Reabsorption

Note: some books mention excretion and water conservation as processes as well. We feel that the excretion is not a process of urine formation, instead it is waste product discarding function. Similarly we feel that the water conservation is achieved by the reabsorption and hence is not a process in itself.

Renal_l7_d2_Plan_Urine_Formation_Fundamentals_SVG

Usually urine formation is measured as volume of urine produced each minute. There are times when we measure the urine output during longer periods of time, for example 24 hours.

Recall that the output  measured in set time intervals is called a rate. For example volume of a substance X excreted in the urine each minute will be called the rate of excretion of the substance X per minute.

As we study the urine formation we will determine the excretion rate of various substances by the following formula:

Excretion rate of substance X = Filtration rate of X + Secretion rate of X – Reabsorption rate of X

Nephron

Nephron is the functional unit of a kidney.  Each kidney contains about one million nephrons (1,000,000 or 10^6). Each individual nephron is able to execute all processes to form urine. A nephron consists of Bowman’s capsule, proximal convoluted tubule, loop of Henle, and the distal convoluted tubule. Distal convoluted tubule opens in the collecting duct.

Renal_l7_d4_Plan_Urine_Formation_Fundamentals_SVG

Urine from the collecting ducts passes through the urinary tract and is excreted by the process of micturition. Surface cells of nephrons are epithelial because the nephrons are continuous with the urinary pathway that opens outside the body.

The loop of Henle enters in the medulla of the kidney. Remaining parts of the nephron are located in the renal cortex.

Types of Nephrons

  • Cortical Nephrons (70%-80%)
  • Juxtamedullary Nephrons (20%-30%)

Cortical Nephrons

70%-80% of the nephrons are cortical. Their primary function is urine formation. Their loop of Henle penetrates for a small distance in the renal medulla. Their participation in the concentration process is minimum. See the blood supply section below to note the difference of the blood supply between the two types of the nephrons.

Juxtamedullary nephrons

20%-30% of the nephrons are located very close to the medulla. This is why these are called Juxtamedullary (near the medulla). These nephrons have long loop of Henle that traverses deep in the medulla. Capillary network around these nephrons is designed to support the process of urine concentration.

Physiologic Blood Supply of the Kidney

About 22% of the cardiac output in healthy individuals goes to both of their kidneys. Hence, kidneys receive about 1100ml/minute blood supply for a person with 5L/m cardiac output. Blood flow to the kidneys can be calculated by the following formula:

Blood supply to both kidneys = CO x 0.22

= 5L/m x 0.22

=1100 ml/m

Glomerulus

Glomerulus is a tuft of capillaries present in the Bowman’s capsule of a nephron. Blood arrives in the glomerulus via the afferent arterioles. Efferent arterioles take the blood out of the glomerulus and into the peritubular capillaries.

Glomerulus is covered by the visceral epithelial cells of the Bowman’s capsule. Glomerular capillary endothelial cells, basement membrane, and the visceral epithelial cells o the Bowman’s capsule form the interface between the blood and the urine compartments.

Renal_l7_d6_Plan_Urine_Formation_Fundamentals_SVG

Hydrostatic pressure in the glomerular capillaries is higher (60 mmHg) than the other capillaries in the body (30 mmHg).

Cortical Nephron vs. Juxtamedullary Blood Supply

Efferent arterioles from the glomerulus of the cortical nephron form a rich capillary meshwork around the corresponding nephron. This meshwork finally coalesce to form the venous end of the blood supply. These peritubular capillaries help with the urine formation, but have limited role for the urine concentration.

Efferent arterioles from the glomeruli of the Juxtamedullary nephrons on the other hand form the capillary network in the early part, however, the efferent arteriole extend deep in the medulla next to the corresponding nephron’s loop of Henle. This long extension is called vasa recta. Vasa recta helps juxtamedullary nephron with the urine concentration.

Renal_l7_d5_Plan_Urine_Formation_Fundamentals_SVG

Stages of the Urine Formation

Filtration

Water and other substances are filtered from the glomerular capillaries to enter the bowman space. Initially substances are filtered regardless of the body’s need of them. Think of it as kidney decide to throw everything out in the ruine. As this fluid moves through the nephron reabsorptive processes reuptake the substances that we need and bring them back into the blood stream. Anything that is not picked up is excreted.

Reabsorption

As the fluid moves through the nephrons various active and passive processes pick up the substances that are needed in the body. Some substances are completely picked up, while only a partial amount is picked up  for some substances.

It is important to note that the proximal convoluted tubules and medullary thick ascending limb of the loop of Henle are the major sites of active reabsorption. These areas require a lot of ATP to function. For this reason hypoxic/ischemic conditions damage cells in these two sites before damaging cells in the other parts of the nephron.

Tubular Secretion

Some of the substances especially poisons and drugs are actively transported from the peritubular capillaries into the lumen of the nephron. This process is called tubular section.

Notes

  • The renal processes are not uniformly applied to all substances.
  • These processes can be altered according to the need of a substance. For example if we need to eliminate a substance then then filtration and secretion can increase, and reabsorption can decrease.

Schematic for further discussion

We will use following schematic diagram to represent this setup.

Renal_l7_d8_Plan_Urine_Formation_Fundamentals_SVG

Some Examples of the Renal Processes

  • Glucose: filtered and completely reabsorbed
  • Inulin: filtered, neither reabsorbed nor secreted.
  • PAH: 20%-30% filtered, rest is completely secreted, not reabsorbed.

 

Categories
Renal Physiology

Renal Physiology – General Concepts

Kidneys perform following categories of functions:

  • Homeostasis
  • Urine Formation
  • Hormone Secretion

Homeostasis

Kidney play a critical role to maintain healthy serum, interstitial, and intracellular  environments. Here are the some of the homeostatic functions that kidneys perform:

  • Acid-base balances (Davenport diagram is a must for medical students to understand.)
  • Serum electrolyte concentrations in varying external and internal situations. (Knowing kidney’s role to maintain Na+, K+, Ca++, H+, PO4, NH3, etc. is critical.)
  • Total body fluid and its distribution in various compartments is influenced by the kidneys.
  • Body fluid osmolarity

Urine Formation

Kidney has a number of functions that help with the homeostasis. One result of this is to excrete extra water, electrolytes, and waste products.

Following renal Processes are used for Homeostasis

  • Filtration. Passive movement of the water and electrolytes from the serum into the nephron (glomerular capsule).
  • Reabsorption. Active and passive movement of the filtrate back into the interstitium and blood compartment.
  • Secretion. Active movement of the substances from the serum to the nephron at any point other than the glomerulus.
  • Excretion. discarding the waste products to the bladder and eventually out of the body.

Hormone Secretion

Kidneys make and release following hormones in the blood:

  • Vitamin D conversion to its active form.
  • Renin secretion helps with blood pressure and blood volume.
  • Erythropoietin helps with the RBC concentration (hematocrit).

Hormones Acting on the Kidneys

Following hormones influence kidney’s function:

  • Antidiuretic Hormone (ADH).
  • Atrial Natriuretic Hormone (ANH).
  • Renin-Angiotensin-Aldosterone System.