Categories
Renal Nephrology Renal System

BUN:CR Ratio

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Disclaimer:

This is not a prescription. Using medicines without the guidance of a licensed provider  can be lethal.

 

  1. >20:1 prerenal.
    Example: dehydration
  2. 10-20:1 normal or postrenal.
    Example:kidney stones.
  3. <10:1 intrarenal.

Example: A TN, glomerulonephritis.

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Categories
Nephrology Renal System

Acute Kidney Injury (AKI)

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Disclaimer:

This is not a prescription. Using medicines without the guidance of a licensed provider  can be lethal.

 

The KDIGO guidelines  define AKI as follows:

1.  Increase in serum creatinine  by _>0.3 mg/dL  within 48 hours, or

2.  Increase in serum creatinine  to _>1.5 times baseline,  which is known or  presumed to have occurred  within the prior seven days, or

3. Urine volume <0.5 ml-/kg/Peur  for six hours

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Categories
Pharmacology Renal Pharmacology Renal System

EXPLORING DIURETICS

Diuretics forms one of the base pillars in treating hypertension and edema. These groups of drugs increases  rate of urine flow. Based on their mechanism of action their efficacy varies. Before moving into diuretics I would recommend to revise renal physiology which will make it easier to get deeper and clear concept of mechanism of diuretics. In this section I will not go into details of each and every diuretics, I would rather try to provide concept and differentiating feature based on mechanism of action and adverse effects.

ADVERSE EFFECTS OF DIURETICS

Efficacy

Class of diuretics Example
Carbonic Anhydrase Inhibitors (CAI) WEAK Acetazolamide
Osmotic diuretics WEAK Mannitol
Loop diuretics HIGH Furosemide
Thiazide MEDIUM Hydrochlorothiazide
Potassium sparring diuretics WEAK

Amiloride (Sodium channel inhibitors)

Spironolactone (Aldosterone receptor antagonist)

Lets revise different section of nephron, (see the figure)

  1. Bowman’s capsule
  2. Proximal Convoluted Tubule (PCT)
  3. Loop of Henle (LOH), Thin descending loop
  4. Loop of Henle (LOH), Thin ascending loop
  5. Loop of Henle (LOH), Thick ascending loop
  6. Distal Convoluted Tubule (DCT)
  7. Cortical collecting tubule
  8. Medullary collecting tubule

Different drugs mention above have different sites for action, they reason why their efficacy and side effects varies from each other. Action of drugs:

Site of nephron Action of drugs
1.      Bowman’s capsule
2.      Proximal Convoluted Tubule (PCT) Carbonic Anhydrase Inhibitors
3.      Loop of Henle (LOH), Thin descending loop Osmotic diuretics acts here (Osmotic Diuretics also acts in Proximal tubule)
4.      Loop of Henle (LOH), Thin ascending loop
5.      Loop of Henle (LOH), Thick ascending loop Loop diuretics
6.      Distal Convoluted Tubule (DCT) Thiazides diuretics
7.      Cortical collecting tubule

 

Potassium sparing diuretics

Potassium sparing diuretics also acts in late distal tubule.

8.      Medullary collecting tubule

MECHANISM OF ACTION

As the normal mechanism of each section of the varies, so drugs acting on different section of nephron have different side effects, though their ultimate goal is to increase the rate of flow of urine.

Mechanism of action of these groups of drugs

  1. Carbonic Anhydrase Inhibitors

Carbonic Anhydrase Inhibitors

Acts in Proximal Convoluted Tubules

Inhibits carbonic Anhydrase

Increases excretion of NaHCO3

Increased rate of flow of urine

  1. Osmotic diuretics

Osmotic diuretics

Acts in proximal tubules and thin descending loop of Henle, thin ascending loop of Henle

Due to osmotic effect, increases excretion of water

Increased rate of flow of urine

  1. Loop diuretics

Loop diuretics

Acts in thick ascending loop of Henle

Blocks sodium, potassium, chloride co transporter

Increases sodium, potassium, chloride excretion

Increased rate of flow of urine

  1. Thiazides

Thiazides

Acts in Distal Convoluted Tubules (DCT)

Blocks sodium chloride transporter

Increased excretion of NaCI

Increased rate of flow of urine

  1. Potassium sparing diuretics (Acts in late distal tubule and collecting tubules)

They can be of two types:

  1. Sodium channel blockers
  2. Aldosterone receptor antagonists

           Sodium channel blockers

       Blocks sodium channel

             Increases sodium excretion and increases potassium retention

Increased rate of flow of urine

      Aldosterone receptor antagonists

Acts as antagonist in aldosterone receptor 

Promotes sodium and chloride excretion without concomitant potassium loss

Increased rate of flow of urine

ADVERSE EFFECTS of these groups of drugs

Side effects of Carbonic Anhydrase Inhibitors

Hyper Hypo
Apnea Potassium
Metabolic acidosis

Ataxia

Tinnitus

Side effects of Osmotic Diuretics

  Hypo
Natremia

Volemia

Fluid and electrolytes imbalance

Acidosis

Dehydration

Urinary retention

Side effects of Loop Diuretics  

Hyper Hypo
Urea

Glucose

Tension

Volemia

Magnesium

Potassium

Sodium

Calcium

Metabolic Alkalosis

Arrhythmias

Ototoxicity

Side effects of Thiazide diuretics

Hyper Hypo
Urea

Glucose

Calcium

Tension

Volemia

Potassium

Sodium

Magnesium

Metabolic Alkalosis

Azotemia

Side effects of Potassium sparing diuretics

Hyper Hypo
Potassium Sodium
Metabolic Acidosis

Gynecomastia

Impotence

ADVERSE EFFECTS OF DIURETICS

Note:

Hyper Sodium: Hypernatremia

Hyper Potassium: Hyperkalemia

There are many more side effects, and more detailed mechanism of action, but it is important to have base concept before moving details of each drugs.

HAPPY READING.

If you find it fruitful, do not hesitate to share the information in your friends circle.

 

 

Dr Bivek Singh

Academic coordinator (MBBS)

Author “A journey into the human body”

Author “Pharmacology Simplified”

Board of Directors (Medical Outreach Nepal, USA)

biveksingh@hotmail.com

www.facebook.com/drbiveksingh

 

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.
Categories
Anatomy Uncategorized

Kidney Anatomy – General Features

Color

Kidney in the fresh state has reddish-brown.

Dimensions

  • 11 cm long
  • 6 cm wide
  • 3 cm thick

Weight

  • Males: 150 g
  • Females: 135 g

General Relations

  • Retroperitoneal organ
  • Lies on the ventral surface of the quadratus lumborum muscle.
  • Lateral to the psoas major, psoas minor, and the spinal column.
  • Middle parenchyma is called Medulla and the outer parenchyma Covering the medulla is called Cortex

Renal Capsules and Fasciae

True or renal capsule is a thin sheet of fascia that can be easily peeled in a healthy individual. In some pathologies this sheet can become scarred and firmly adherent to the kidney surface.

Hilum

A vertical cleft on the concave medial side of the kidney. From anterior to posterior hilum contains renal vein, renal artery, and renal pelvis. Renal hilum continues inwards to contain renal vessels, lymphatics, renal pelvis, major and minor calyces, nerve plexus, and some fat.

Right Kidney (1.5 cm lower than the left kidney)

  • Upper pole at T12.
  • Right kidney’s hilum is 5cm from the median plane and below the transpyloric plane.
  • Below the spinous process of the L1 vertebra.
  • Related to rib 12.

Structures anterior to the right kidney

  •     Right suprarenal gland
  •     Right colic flexure
  •     Small intestine
  •     Part of the descending duodenum
  •     Liver

Structures posterior to the right kidney

  •     12th rib
  •     Transverse process of L1 vertebra
  •     Diaphragm
  •     Psoas Major
  •     Quadratus Lumborum
  •     Tendon of Transverse Abdominis muscle

Left Kidney (1.5 cm higher than the right kidney)

  • Upper pole at T11
  • Hilum of the left kidney is 5cm from the median plane at the lower border of the spinous process of the L1 vertebra.
  • Transpyloric plane passes through the hilum of the left kidney and L1. (Remember L for Left).
  • Related to ribs 11 and 12

Structures anterior to the left kidney

  •     Left suprarenal gland
  •     Stomach
  •     Jejunum
  •     Left colic flexure
  •     Pancreas
  •     Spleen

Structures posterior to the left kidney

  •     11th and 12th ribs
  •     Transverse process of L1 vertebra
  •     Diaphragm
  •     Psoas Major
  •     Quadratus Lumborum
  •     Tendon of Transverse Abdominis muscle