# Medical Physiology/Renal Physiology
## Overview of Module

Should summarize the contents of the module & should be detailed enough to give the reader a quick revision.

## Clinical Examples

Provide Clinical examples relevant to the section

## Clinical Relevance

Provide Clinical examples relevant to the module

## The Basics

The functioning of kidneys can be divided into three major categories:
* Excretory, in that the kidneys ensure excess substances are excreted in urine appropriately
* Regulatory, in that the kidneys regulate a constant volume and composition of body fluids. This is accomplished by altering the excretion of solutes and through water balance (osmoregulation)
* Endocrine, in that the kidneys are where three hormones are synthesized and secreted: renin, erythropoietin, and 1,25-dihydroxycholecalciferol.

## Renal Anatomy

Located in the retroperitoneal cavity of the body, the kidneys are bean-shaped organs that have three main regions. In the outer region is the cortex, which is just deep to the kidney capsule. In the central region is the medulla, which is itself divided into two parts, the outer medulla and the inner medulla. Within the outer medulla, there are two "stripes": an outer stripe and an inner stripe. At the deepest tip of the inner medulla is the papilla, which empties into the major and minor calyces, pouch-like extensions of the ureter. From here, the ureter extends into the bladder, where urine is stored until elimination.

### The Nephron

Nephrons are the functional units of the kidney. There are about 1.2 million nephrons in each kidney. The nephron is composed of two smaller entities: a glomerulus and a renal tubule. The glomerulus is a capillary network that emerges from an afferent arteriole. It is surrounded by the Bowman's capsule or Bowman's space(Lumen of glomerular capsule), which is continuous with the first part of the nephron.
The first step in urine formation is the ultrafiltration of blood across the glomerular capillaries into the Bowman's space . From here, the nephron is a tubular structure that carries out reabsorptive and secretory functions via epithelial cells.
Beginning with the Bowman's space, nephron structure is composed of:
* Proximal convoluted tubule
* Proximal straight tubule
* Loop of Henle (which consists of a thin descending limb, a thin ascending limb, and a thick ascending limb)
* Distal convoluted tubule
* Collecting ducts
Each section has its own unique function, which will be explored in detail later in this chapter.

#### Types of Nephrons

There are two types of nephrons:
* Superficial cortical nephrons, which have their glomeruli in the outer cortex. They have shorter loops of Henle, which dip only into the outer medulla. They operate under normal conditions.
* Juxtamedullary nephrons, which have their glomeruli near the corticomedullary border. They have larger glomeruli, and thus have higher glomerular filtration rates (GFR). Juxtamedullary nephrons' loops of Henle dip deeper into the inner medulla and papilla, and are vital in the concentration of urine. They work especially during periods of high activity.

## Renal Blood Supply

Blood arrives at the kidney through the renal artery. The renal artery branches into the interlobar arteries, arcuate arteries, and the cortical radial arteries.
The smallest of the arteries divide even further into sets of arterioles
* Afferent arterioles supply blood to the first capillary network, the glomerular capillaries. This is where ultrafiltration occurs.
* From the glomerular capillaries, blood flows to the efferent arterioles, which supply blood to the second capillary network, the peritubular capillaries. From the peritubular capillaries, blood exits through the small veins and finally, the renal vein.
In Summary: Renal a. → Segmental a. → Interlobar a. → Arcuate a. → Interlobular a → Afferent arterioles → Glomerular capillaries → Efferent arterioles → Vasa recta → Peritubular capillaries → Small vv. → Renal v.
However, there is a difference between the vasculature of the superficial cortical nephrons and the juxtamedullary nephrons.
* The superficial cortical nephrons have peritubular capillaries which branch off the efferent arterioles, and provide nutrients to the epithelial cells which are present there. In addition to serving the epithelial cells, these capillaries supply the blood for reabsorption and secretion.
* The juxtamedullary nephrons have a special structure within the peritubular capillaries, called the vasa recta. The vasa recta is a long, hairpin-shaped set of blood vessels that run next to the loops of Henle. It also functions as osmotic exchangers for the concentration of urine.

## Body Fluids

Water is the main constituent of the internal body environment, comprising an average of 60% of body weight.

### Water Distribution
#### Total Body Water (TBW)

About 60% of body weight is comprised of water. There is a slight variation depending on gender and the amount of fat in the body. (Water content is inversely proportional to fat content) Women have lower percentages of water compared to men. This is because women have a higher percentage of adipose tissue.
Thus,
* Thin men have the higher percentage of weight as water at ~70%
* Obese women have the lowest percentage of weight as water at ~50%
How is this clinically relevant? This is because changes in body weight can be used to estimate any changes in the body water content.
Total body water (TBW) is distributed between two major compartments: the intracellular fluid (ICF) and extracellular fluid (ECF).
Of TBW,
* ~2/3 is in ICF
* ~1/3 is in ECF
When expressed as body weight,
* 40% of body weight is in ICF (2/3 of 60%)
* 20% of body weight is in ECF (1/2 of 60%)
** ECF is further divided into two compartments
*** Interstitial Fluid (ISF) (3/4 of the ECF)
*** Plasma (1/4 of the ECF)
*** A negligible third compartment, the transcellular compartment includes the cerebrospinal, pleural, peritoneal, and digestive fluids.

#### Intracellular Fluid (ICF)

'Def.' the water inside the cells, where all solutes within are dissolved
It consists of 2/3 of TBW (or 40% of body weight). The major cations are K$^+$ and Mg$^{2+}$. The major anions are proteins and organic phosphates (e.g., ATP, ADP, AMP)

#### Extracellular Fluid (ECF)

'Def.' the water outside the cells
It consists of 1/3 of TBW (or 20% of body weight). ECF is further divided into two separate compartments:
* Plasma, the fluid that circulates in the blood vessels.
** Aqueous compartment of the blood
** Constitutes about 50% of blood volume (the other 45% is consisted of blood cells, such as RBC, WBC, platelets).
*** The percent of blood volume that are made up of RBC is called the hematocrit.
**** This is ~45%, and higher in males.
** Plasma proteins make up about 7% of plasma
*** Thus, only 90% of plasma is plasma water
* ISF, which bathes the cells.
** An ultrafiltrate of plasma
** Has nearly the same composition as plasma (with the exception of plasma proteins and blood cells)
The major cation of ECF is Na$^+$, and the major anions are Cl$^-$ and Bicarbonate (HCO$_3$$^-$).

### Movement of Water Between Compartments
#### Isosmotic Volume Contraction (Diarrhea)

Diarrhea, characterized by a significant loss of fluids for the patient, will induce hyperosmotic volume contraction (dehydration) if left untreated.