Week 11: Kidneys

Renal means

pertaining the to kidneys

Functions of the kidneys

1. Regulate the water and ionic composiiton of the body

2. Excrete waste products in the urine

3. Excrete foreign chemicals

4. Produce glucose during prolonged fasting (Gluconeogenesis)

5. As an endocrine gland - Release factors and hormones into the blood (Renin, 1,25-dihydroxyvitamin D, and

   Erythropoietin)

Examples of metabolic waste products the kidneys excrete

• Urea (from protein)

• Uric acid (from nuclei acid)

• Creatinine (from muscle creatine)

Erythropoietin produced by the kidney does what

controls erythrocyte production

Renin produced by the kidney does what

is an enzyme that controls the formation of anghiotensin, which influences blood pressure and sodium balance

1,25-dihydroxyvitamin D produced by the kidney does what

influences calcium balance

Kidneys location

Back of the abdominal wall in the retroperitoneal space - behind the peritoneum (lining of the abdominal cavity)

Urine flow sequence

Kidneys → Ureters → Bladder → Urethra → Environment

Ureters function

transport urine from kidneys to bladder

Bladder function

stores urine until voided from body

Urethra function

carries urine from bladder to the outside of the body

Blood flow through kidneys sequence

Aorta → Renal arteries → Renal circulation → Renal veins

Structural and Functional unit of the kidneys

Nephrons

Nephron consists of

Renal corpuscle and a Renal tubule

Juxtamedullary nephrons

Renal corpuscle located in cortex just next to the medulla and have long loops of Henle that penetrate deep into the medulla

Two types of nephrons

• Juxtamedullary

• Cortical

% of nephrons that are Juxtamedullary

15%

% of nephrons that are Cortical

85%

Cortical nephrons

have short or no loops of Henle

Efferent arterioles of juxtamedullary nephrons give rise to

Vasta recta - long looping capillaries

Efferent arterioles of cortical nephrons give rise to

peritubular capillaries

About how many nephrons are in 1 kidney

1 million

Renal corpuscle consists of

Glomerulus (capillary tuft) and a Bowman’s Capsule (which the tuft protrudes into)

Bowman’s Space

within the Bowman’s capsule from which fluid flows into the start of the nephron tubule

Fluid flow sequence in Nephron

Glomerulus → Bowman’s Capsule → Proximal Convoluted Tubules→ Loop of Henle (descending and ascending limbs) → Distal Convoluted Tubules → Collecting ducts (cortical and medullary)

Substance filtration sequence in the renal corpuscle

Capillary pores b/w endothelial cells → basement membrane → filtration slits b/w the foot processes (pedicles) → enters capsular space → lumen of proximal convolutes tubule

Multiple collecting ducts in the kidneys join and empty into

the renal pelvis, from which urine flows through the ureters → bladder

The capillaries of the glomerulus are

fenestrated, which allows large amounts of solute-rich fluid to pass between the epithelial cells

Glomerulus is supplied with blood by

an Afferent arteriole

As blood flows through the Glomerulus, how much plasma is filtered into the Bowman’s capsule

20%

Glomerulus blood is drained by

an Efferent arteriole

Efferent arteriole leaving the Glomerulus

branch into peritubular capillaries, which supply the tubule

Only capillaries in the body that are fed and drained by an arteriole

glomerular capillaires

Vasa recta

long capillary loop that runs next to the loop of Henle

How many layers of filtration barrier is in the renal corpuscle

3

Filtration barriers in the renal corpuscle

1. Capillary endothelium

2. Glomerulus basement membrane

3. Bowman’s capsule epithelium (podocytes); mesangial cells

Podocytes

cells making up the epithelial lining of Bowman’s capsule - inner layer of the glomerular filtration barrier

Podocytes posses a large number of

extensions/foot processes, which surround the basement membrane

Filtration slits

clefts between the podocytes; as the filtrate passes through them, it enters the capsular space

Mesangial cells

modified smooth muscle cells in the glomerulus that helps regulate the blood flow in the glomerulus by contraction, which reduces the surface area available for filtration

Fluids free of proteins from the glomerulus filter into the

Bowman’s space

Juxtaglomerular Apparatus

composed of the macula densa (patch of tubular wall cells at end of ascending limb of the loop of Henle) and juxtaglomerular (JG) cells (afferent arteriole wall cells that secrete renin)

Macula Densa

Apart of Juxtaglomerular apparatus - patch of tubular wall cells at end of ascending limb of the loop of Henle

Macula Densa cells function

• senses changes in the NaCl content of the filtrate

• Helps to regulate sodium balance and blood pressure

Juxtaglomerular (JG) cells

Apart of Juxtaglomerular apparatus - afferent arteriole wall cells that secrete renin in response to decrease in stretch)

3 basic renal processes

1. Glomerular filtration

2. Tubular reabsorption

3. Tubular secretion

Tubular secretion

Movement of a substance from Peritubular capillary to Tubular Lumen

Most important substances that enter the forming urine by tubular secretion

Hydrogen ions and Potassium ions, some creatinine (organic anions) as well

Tubular secretion is important mechanism for

• Disposing of drugs and drug metabolites

• Eliminating undesired substances or end-products that have been reabsorbed by a passive process

• Removing excess K+ from the blood

• Controlling blood pH

Tubular Reabsorption

Movement of a substance from Tubular Lumen to Peritubular Capillary

• Can occur through transcellular or paracellular transport

• transport can be active or passive

Amount excreted =

Amount filtered + Amount secreted - Amount reabsorbed

Urine formation begins with

glomerular filtration - essentially protein-free plasma into Bowman’s space

Glomerular Filtration

a bulk-flow passive process in which hydrostatic pressure forces water and all low-molecular weight substances through a filtration barrier

The glomeruli in the kidney are a much more efficient filter compared to other capillary beds in the body b/c:

• the glomerular filtration barrier has a large surface area and is very permeable to water and solutes

• the glomerular capillary blood pressure is higher (60 mmHg) than in typical systemic capillary

Main reabsorptive force keeping water in the glomerular capillaries

the osmotic force due to the presence of protein in the plasma

Hematuria

Blood cells in the urine

Proteinuria

Protein in the urine

Hematuria or proteinuria indicates

potential problems with the glomerular filtration barrier

Glomerular filtration rate per day

180 L/day of essentially protein-free plasma

Glomerular filtrate contains

all plasma substances other than proteins (and substances bound to proteins) in virtually the same concentrations as in plasma

Glomerular filtrate concentration is the same as

plasma

Glomerular filtration pressure is driven by

Starling forces - hydrostatic pressure in the glomerular capillaries and is opposed by both the hydrostatic pressure in Bowman’s space and the osmotic force due to the proteins in the glomerular capillary plasma

Forces involved in glomerular filtration

• Glomerular capillary blood pressure

• Fluid pressure in Bowman’s space

• Osmotic force due to protein in plasma

Force involved in glomerular filtration FAVORING filtration

Glomerular capillary blood pressure

Force involved in glomerular filtration OPPOSING filtration

• Fluid pressure in Bowman’s space

• Osmotic force due to protein in plasma

GFR

Glomerular Filtration Rate

Glomerular Filtration Rate (GFR)

the volume of plasma filtered from glomerular capillaries into Bowman’s space per unit time

Glomerular Filtration Rate (GFR) is determined by

• net filtration pressure

• the permeability of the corpuscular membranes

• the filtration surface area

Glomerular filtered load =

GFR × plasma concentration of filtered substance

Constriction of afferent arteriole =

decreased GFR

Dilation of efferent arteriole =

decreased GFR

Constriction of efferent arteriole =

increased GFR

Dilation of afferent arteriole

increased GFR

Renal tubule

a long cylinder, extending from Bowman’s capsule to the collecting ducts of the nephrons; consists of several parts

Parts of the renal tubule

• Proximal convolutes tubule

• Loop of Henle

• Distal convoluted tubule

• Collecting duct

Metabolism by the tubules

• Renal tubule cells can synthesize glucose during fasting and add it to the blood

• Can catabolize certain organic substances such as peptides, taken up from either the tubular lumen or peritubular capillaries. Catabolism eliminates these substances from the body as if excreted into the urine

By the time the filtrate reaches the medullary collecting ducts

modification has been finished and the finished product is urine

The most abundant cation in the filtrate

Na+

Substances to which the tubular epithelium is permeable are reabsorbed by diffusion

because water reabsorption creates tubule-interstitial-fluid-concentration gradients

Active reabsorption of a substance requires the participation of transporters in the

apical membrane (between tubular lumen and cell) or basolateral membrane (between interstitial space next to capillaries and cell)

Tubular reabsorption rate is high for

nutrients, ions, and water

Tubular reabsorption rate is low for

waste products

Transport maximum is exhibited by

substances moved by mediated transporters

Regulation of membrane channels and transporters

achieved by hormones and paracrine or autocrine factors

If the filtered load of a substance exceeds the reabsorptive transport maximum

the substance will be excreted in the urine

Role of proximal tubule

reabsorbs most filtered water and solutes, and is the major site of tubular secretion, with the exception of K+ ions

Role of Loop of Henle

reabsorbs large amounts of major ions and to a lesser extent, water

Diabetic nephropathy

when diabetes mellitus (hyperglycemia) is poorly controlled. Filtered load of

glucose exceeds reabsorptive transport maximum so glucose “spills” into the urine, which can lead to decrease in renal function

Familial Renal Glucosuria

defect in the glucose transporter

Renal Clearance of any substance

is the volume of plasma from which that substance is completely removed (“cleared”) by the kidneys per unit time (e.g., units are in mL/min)

Clearance formula

C_s = U_sV / P_s

= (urine concentration of S x Urine volume per unit time) / plasma concentration of the substance

Importance of Glucose clearance

it is important not to lose glucose in the urine, it is completely reabsorbed so its renal clearance rate is zero in healthy people

Renal clearance of substance > GFR means

the substance must undergo tubular secretion

Renal clearance of substance < GFR means

the substance must undergo some reabsorption

GFR of Inulin

= clearance rate

small carbohydrate that is filtered but not reabsorbed or secreted; infused experimentally

How to estimate GFR clinically

with Creatinine clearnace b/c it is filtered, not reabsorbed, and secreted only a little

Renal plasma flow is estimated by

the clearance of a substance that is filtered, not reabsorbed, and 100% secreted. All that enters the kidneys from the blood is cleared.

Micturition

Urination

Spinal micturition reflex is

involuntary

Spinal micturition reflex

• Bladder distension stimulates stretch receptors that trigger spinal reflexes

• These reflexes lead to contraction of the detrusor muscle (bladder smooth muscle).

• mediated by parasympathetic and sympathetic neurons

• mediated by relaxation of both the internal and the external urethral sphincters (inhibition of neural input)