Chapter 25 - The Renal System (2)

What is the function of the kidneys?

~200 L (~20-25 gallons) of fluid filtered from blood by kidneys every single day

• maintaining the composition of the body’s extracellular fluids by filtering the blood

What 5 things are involved with the kidneys?

1. regulate total body water volume

2. regulate concentration of ions in ECF

3. acid-base balance

• potassium and sodium balance

4. remove toxins, metabolic wastes, and other foreign substances

5. hormone production-EPO and renin

External Gross Anatomy of the Kidneys

medial portion is concave

• renal hilum

• renal fascia

• perirenal fat capsule

• fibrous capsule

Renal Hilum

ureters, renal blood vessels, lymphatics, and renal nerve supply enter here

Renal Fascia

dense connective tissue

• anchors kidneys to surrounding structures

Perirenal Fat Capsule

fat mass surrounding kidneys

• cushions kidneys from physical trauma

Fibrous Capsule

thin, transparent capsule

• prevents disease from spreading to kidneys from other parts of body

What are the 3 major internal regions of the kidney?

1. renal cortex

2. renal medulla

3. renal pelvis and calyces

Renal Cortex

outer region of kidney where filtration of blood and EPO production occurs

Renal Medulla

contains several renal pyramids → packed with capillaries and urine-collecting tubules

• water reabsorption, electrolyte balance, disposal of waste

Renal Pelvis and Calyces

open spaces in each kidney

• minor and major calyces

• function = urine collection from renal medulla and drainage from kidneys

Minor Calyces

found at tip of each renal pyramid

• minor calyces combine to form major calyces

Major Calyces

combine to form renal pelvis

What 5 arteries supply blood to the kidneys?

1. renal arteries → divide into smaller vessels to serve major regions of kidneys

   1. segmental arteries

   2. interlobar arteries → travel between renal pyramids

   3. arcuate arteries → arc over base of each pyramid

   4. cortical radiate arteries → supply renal cortex

What 4 veins bring fluids away from the kidneys?

1. cortical radiate veins

2. arcuate veins

3. interlobar veins

4. renal veins

Renal Plexus

autonomic nerve fibers and ganglia

• sympathetic vasomotor fibers regulate blood supply to each kidney

Sympathetic Vasomotor

adjusts diameter of renal arterioles to increase or decrease blood flow to filtering structures of kidneys

What is the importance of changing blood flow to the kidneys?

supplying more blood → filters more blood

• directly affects blood plasma, waste removal, ion concentrations, etc.

Kidney Microanatomy: Nephron

functional unit of the kidney

• function = filters blood to form filtrate and eventually urine in the kidneys

What is the general structure of the nephron?

each nephron contains a renal corpuscle and renal tubule

• renal corpuscle → filters blood to form the filtrate

• renal tubule → reabsorbs some substances from the filtrate and secretes other substances into the filtrate

What happens to substances that are reabsorbed? Secreted?

reabsorbed → substances initially taken out are brought back into the system

secreted → substances are disposed of in urine

Renal Corpuscle

located entirely within renal cortex

• subdivisions:

  • glomerulus

  • glomerular capsule

Glomerulus

cluster of capillaries

• blood enters glomerulus vias afferent arteriole, leave via efferent arteriole

  • keeps pressure high → allows for the formation of filtrate

• capillaries are very porous (fenestrated) → some fluid and substances in blood easily filtered out of capillary

Filtrate

what fluid is called; raw material used to produce urine (NOT THE SAME AS URINE)

Glomerular Capsule

double-layered structure that surrounds capillaries

• is continuous with renal tubule

• inner layer has podocytes (foot cell) with foot processes

• function = catches the filtrate that is formed by the capillaries

Renal Tubules & Collecting Duct

regions in renal cortex, extends into renal medulla, then returns to renal cortex

• hairpin-like structure benefit = can exchange more material, reabsorb more substances → important for forming highly concentration urine when necessary

• subdivisions of the renal tubule:

  • proximal convoluted tubule (PCT)

  • nephron loop

  • distal convoluted tubule (DCT)

Proximal Convoluted Tubule (PCT)

leads immediately off from glomerulus

• located in renal cortex

• large cuboidal epithelial cells with dense microvilli

  • increases surface area → increases exchange and reabsorption of materials

Nephron Loop

travel between renal cortex and renal medulla

• descending limb → continuous with PCT; carries filtrate downward

• ascending limb → continuous with DCT; carries filtrate upward

• function = allows the kidneys to vary the concentration of urine according to how much water is reabsorbed at nephron loop

Distal Convoluted Tubule (DCT)

located in cortex, composed of small cuboidal epihtelia

• smaller diameter than PCT, contains NO microvilli

  • less surface area → reabsorption is lower than PCT

Collecting Ducts

• each collecting duct receives filtrate of multiple nephrons

• collecting ducts fuse together, dump urine into minor calyces

2 important cell types:

1. principal cells

2. type A and type B intercalated cells

Principal Cells

maintain Na+ balance in body by reabsorbing Na+ from filtrate

• YES it would affect the reabsorbing of other substances

Type A and Type B Intercalated Cells

help maintain acid-base balance by secreting or reabsorbing H+ or HCO^3-

Cortical Nephrons

located almost entirely in the cortex

• small portion of nephron loop found in renal medulla

Juxtamedullary Nephrons

nephron loop deeply invades renal medulla

• important for forming highly concentration urine

What does the glomerulus capillary do?

maintains high pressure to increase filtrate production

Peritubular Capillaries

capillaries arising from efferent arteriole

• cling to proximal and distal tubules of cortical nephrons

  • function = reabsorb water and solutes from cells in renal tubules

• empty into cortical radiate veins → returns to circulation (reabsorption and concentration control should be done)

Vasa Recta

found only on juxtamedullary nephrons

• run parallel to long nephron loop

• helps form concentrated urine

Juxtaglomerular Complex

region of nephron where portion of DCT contracts afferent and efferent artieroles

• overall function = regulate pressure and filtration rate in the glomerular capillaries

What 3 cellular modifications exist at the juxtaglomerular complex?

1. macula densa

2. granular cells

3. extraglomerular esangial cells

Macula Densa

chemoreceptor cells

• function = monitor NaCl content of filtrate in DCT

How does the rate of filtrate formation affect NaCl concentration in the DCT? What happens to the afferent arteriole in response?

1. blood supply is low → low amount of sodium in filtrate → takes more time to filter → more sodium filtered out → LOW NaCl concentration in DCT

2. afferent arteriole dilate to increase the blood supply to capillaries

Granular Cells

specialized smooth muscle cells

• found in walls of afferent arteriole

• activated by macula densa and stretch of afferent arteriole walls

• contain granules that secrete renin → efferent arteriole constricts → slower drainage of blood out of capillary → increases pressure → increases filtrate formation → fixes the problem

  • low filtrate formation = increased renin release

  • RENIN MOSTLY AFFECTS THE EFFERENT ARTERIOLE

Extraglomerular Mesangial Cells

packed between tubule and arterioles

• function = facilitate communication between macula dense and granular cells

Diuresis Step 1: Glomerular Filtration

production of a cell and protein-free filtrate

• pressure forces fluid out of glomerular capillary and into glomerular capsule

• filtration membrane → allows passage of water and small solutes into glomerular capsule

Diuresis

urine formation

What do the foot processes of podocytes do?

create filtration slits → slits prevent passage of macromolecules / large-sized materials into filtrate

Filtration Pressures

pressures that force fluid into or out of glomerulus

Outward Pressure

promotes filtrate formation by forcing fluid out of glomerular capillaries

Hydrostatic Pressure in Glomerular Capillaries (HP_gc)

blood pressure in the glomerular capillaries that “pushes” fluid out of glomerulus (55 mm Hg)

Inward Pressures

oppose filtrate formation by putting fluid back into the glomerular capillaries

Hydrostatic pressure in capsular space (HP_cs)

filtrate in the glomerular capsule “pushes into” glomerular capillaries (15 mm Hg)

Colloid osmotic pressure in glomerular capillaries (OP_gc)

proteins that are still in capillaries will “pull” water back in (30 mm Hg)

Glomerular Filtration Rate (GFR)

the total volume of filtrate formed per minute for all nephrons in the kidneys

What 3 factors affect Glomerular Filtration Rate?

1. net filtration pressure (NFP) → want to keep it around 10 mm Hg

2. surface area of capillaries → more SA promotes filtration

3. filtration membrane permeability

Where does filtration occur along of a glomerular capillary?

along the ENTIRE LENGTH of a glomerular capillary

What is the normal Glomerular Filtration Rate?

normal GFR is 90-120 mL filtrate/min

What 2 reasons is the Glomerular Filtration Rate tightly regulated?

1. kidneys need constant GFR to make filtrate and maintain extracellular homeostasis

2. regulating GFR regulates blood pressure in ENTIRE body

What is the primary Glomerular Filtration Rate variable controlled? What happens when it decreases?

HP_gc → when HP_gc decreases → NFP and GFR also decrease

Renal Autoregulation of GFR (intrinsic)

kidneys adjust resistance to blood flow

• intrinsic controls can maintain GFR for blood pressures ranging 80-180 mm Hg

Myogenic Mechanism

rising systemic blood pressure stretches afferent arteriole

What happens to afferent arteriole in response to stretch?

afferent arteriole contracts (less blood), restricting blood flow into the glomerulus to maintain GFR at desirable rate

Tubuloglomerular Feedback Mechanism

controlled by the macula densa

• macula densa monitors NaCl concentrations

• increase in NaCl in filtrate results in constriction of afferent arteriole

Neural Mechanisms (extrinsic)

the sympathetic nervous system will override renal autoregulation

• norepinephrine is released by the sympathetic system in response to low blood pressure

  • vascular smooth muscle contracts

When will the sympathetic nervous system will override renal autoregulation? Why?

when blood pressure is dangerously low because the sympathetic nervous system releases norepinephrine and afferent arterioles to constrict (this maintains blood volume) and increases blood pressure

Hormonal Mechanisms (extrinsic)

Renin-Angiotensin-Aldosterone mechanism → overall effect is to increase blood pressure

• granular cells of JGC stimulated to released renin

The activation of granular cells to release renin can be initiated by what?

1. stimulation of sympathetic nervous system

2. activated macula densa cells → sense low NaCl concentration due to decreased GFR

3. reduced stretch of arteriole walls → less stretch indicates low blood pressure

Diuresis Step 2: Reabsorption

moving substances from the filtrated back into the blood

• 99% of filtrate is reabsorbed by the body

• substances can either move in between kidney tubule cells or through kidney tubule cells

Paracellular

substances moving between kidney tubule cells

Transcellular

substances moving through kidney tubule cells (requires protein)

Reabsorption of Na+

transcellular (through kidney tubules), active process (requires ATP)

Reabsorption of Nutrients and Ions

can be both transcellular or paracellular

• nutrients are co-transported with Na+ via transcellular route

• ions can be transcellular or paracellular

Reabsorption of Water

can be transcellular or paracellular, passive

• small water molecules → can pass in between kidney tubule cells (paracellular)

What is the most important substance for reabsorption and balance?

sodium (Na+)

Aquaporin

transmembrane protein that allows water to cross plasma membrane of tubule cell and enter tubule cell

What tubule has many aquaporins?

proximal convoluted tubule (PCT)

• water is always absorbed here

When do collecting ducts have aquaporins?

when antidiuretic hormone (ADH) is present

What does any pathway using a transport protein have?

transport maximum (T_m) → specific number of binding sites, so can only move a certain number of molecules at a time (more transport proteins = higher amount absorbed)

What happens when all the transport proteins for a particular substance are bound?

can’t reabsorb anything else

• all transport proteins are busy, so the substance will just leave without reabsorbing

Reabsorption in the Proximal Convoluted Tubule (PCT)

contain villi and microvilli

• all glucose, amino acids, most other nutrients reabsorbed here

• most water and Na+ also reabsorbed here (~65%)

• most electrolytes reabsorbed here

• uric acid and urea also reabsorbed here

Why are villi and microvilli important for reabsorption?

increase surface area → can move more substances

Why is it “weird” that uric acid and urea are reabsorbed in the PCT?

nitrogenous waste → want to get rid of it

Reabsorption in the Nephron Loop

water reabsorption is not coupled to solute reabsorption here (DOES NOT FOLLOW SOLUTE)

• only water can cross the wall of the descending limb

• only solutes can cross the wall of the ascending limb

What is the importance of the difference in permeability between the ascending and descending limb?

allows the nephron to form dilute or concentrated urine

The reabsorption in the Distal Convoluted Tubule and Collecting Duct is hormonally controlled by what 4 things?

1. antidiuretic hormone (ADH)

2. aldosterone

3. atrial natriuretic peptide (ANP)

4. parathyroid hormone (PTH)

Antidiuretic Hormone (ADH)

inhibits urine formation by increasing water reabsorption from filtrate

• aquaporins inserted into collecting ducts

  • amount of ADH is directly proportional to number of aquaporins inserted

Aldosterone

promotes Na+ reabsorption by principal cells of collecting ducts

• decreases urine formation

Atrial Natriuretic Peptide (ANP)

inhibits Na+ reabsorption in collecting ducts

• increases urine formation

Parathyroid Hormone (PTH)

increases reabsorption of Ca²⁺ in the DCT

Diuresis Step 3: Secretion

selectively moving substances from the blood and back into the filtrate (“reabsorption in reverse”)

What is the main site for secretion?

proximal convoluted tubule

What are the 3 functions of secretion?

1. eliminates waste/undesirable material that are passively reabsorbed

2. rids body of excess K+ in DCT and collecting ducts

3. controls acid-base balance and blood pH → secretion of excess H+ or HCO^3-

What is the normal solute concentration of ECF and ICF?

300 mOsm

When is osmolality high? Low?

high → dehydration

low → overhydration

What do kidneys do to osmolality?

balance water, electrolytes, and other substances to maintain the normal osmolality over the long term

Countercurrent Exchange Mechanism

movement of fluids in the opposite direction through the nephron loop allowing exchange of material

Countercurrent Multiplier

occurs in ascending and descending limb of the juxtamedullary nephron loops

• movement of solutes and water out of nephron loop allows for formation of concentrated urine

Countercurrent Exchange

flow of blood through the vasa recta

• vasa recta reabsorbs water to maintain gradient of multiplier

What does the countercurrent multiplier establish?

an osmotic gradient

What mechanisms allows the body to maintain a consistent osmolality?

countercurrent exchange mechanism

What happens to the solute concentration of the medullary space?

solute is going into medullary space, so it increases solute concentration