CHAPTER 15: Renal

Urinary System Anatomy Know every diagram on this pp

Urinary System Homeostasis

Control of extracellular fluid: interstitial fluid and plasma

Control both ECF volume and composition ECF Composition

Electrolytes (Na+, K+, Cl-) Minerals (PO43-, Mg2+, Ca2+) Acid-base balance (HCO3, H+) Toxic products of metabolism (uremic toxins)

ECF Volume

Summary Homeostasis

Digestive and nervous systems indiscriminate Cardiovascular systems only controls blood

pressure The Urinary System (Kidneys) controls composition

of extracellular fluid Homeostasis is the maintenance of the milieu

interieur, based not on what we ingest but what the urinary system keeps

Human Kidney - cut section

25% of cardiac output goes into renal artery at rest

Human Kidney - cut section Key structures to know:

cortex, medulla, pelvis, ureter, artery and vein

25% of cardiac output goes into renal artery at rest

Nephron 1,000,000/human kidney

500,000/dog kidney

proximal tubule

loop of Henle (descending, then ascending limb)

collecting duct

distal tubule

glomerulus

Nephron 1,000,000/human kidney

500,000/dog kidney

Key structures to know: cortex, medulla, pelvis, ureter, artery, vein, nephron and its parts

proximal tubule

loop of Henle (descending, then ascending limb)

collecting duct

distal tubule

glomerulus

Proximal tubule

Surrounded by smooth muscle

Important vessels: Renal artery and vein (1 of each per kidney) Each nephron has:

Afferent and Efferent arteriole Glomerular capillary bed Peritubular capillary bed (also referred to as Vasa recta capillary bed) Is more attracted to positive molecules because it holds a negative charge,

seen in the filtration of netrans; carbs with charges

Surrounded by smooth muscle

3 key renal processes determine what is excreted in urine

Proximal Tubule

Bowmans Space

Filtration

Bowmans or Glomerular

Capsule

1 2 3

Glomerular structure (Key: 3 layers of filtration barrier)

Filtration barrier

Continuous: Limits macromolecular movement across wall to molecules

Filtration Glomerular capillaries

Driven by high hydrostatic pressure (Pc; >50 mmHg) in glomerular capillaries

Highly permeable to water and small molecules

Water, electrolytes (such as Na, K, Cl), amino acids, and glucose are freely filtered

Glomerular filtration rate (GFR) = 125 mL/min in normal person; 4 mL/kg/min in other species)

GFR is large (equivalent to plasma volume every 20 mins in all species)

Highly selective (large molecules such as proteins >30,000 Daltons, are kept in plasma)

About 1/3 of plasma entering glomerulus is filtered into Bowmans space (Filtration Fraction = 33%)

2/3 (67%) of water and small molecules and 100% of large proteins enter peritubular capillary

What gets thru: Water, small solutes (freely) Not macromolecules

Control of GFR Pressure in the glomerular capillaries causes filtration (GFR)

Think of afferent arteriole as a spigot (opening it will increase GFR by increasing pressure in glomerulr capillaries)

The efferent arteriole is like a pressure relief valve (opening it will lower pressure in the glomerular capillaries and reduce GFR).

Angiotensin would increase filtration rate of GFR

Control of GFR An increase in systemic arterial blood

pressure might be expected to increase renal blood flow and GFR

However, if blood pressure increases, there is an automatic constriction of the afferent arteriole

Renal blood flow and GFR do not change Renal autoregulation. Regardless of what

happens to blood pressure, renal blood pressure remains the same

Blood pressure

Reabsorption: Overview Not filtered solutes

Albumin and other large proteins (>30,000 Daltons) Filtered solutes

Tubular Reabsorption and Secretion Subtypes:

Conserved solutes: important for kidney to save (goal = 100% reabsorption) examples: glucose and amino acids

Balanced solutes: kidney balances input with urinary excretion (goal = balance) examples: Na+, K+, H+

Excreted solutes: important to eliminate in urine (goal = excretion) urea, medications (antibiotics)

Water Regulated by Urine Concentrating Mechanism

Conserved Solute Reabsorption

Glucose as an example Sodium-Glucose Linked Transporter (SGLT) in

brush border membrane Secondary active transport SGLT2 early in proximal tubule SGLT1 late in proximal tubule

GLUcose Transporter (GLUT) in basolateral membrane

Facilitated diffusion Normally, >99% of glucose reabsorbed before end

of proximal tubule Amino Acid reabsorption is identical except that

there are different carriers >99% in proximal tubule

Drug Industry: Developing SGLT inhibitors for treatment of metabolic syndrome

Metabolic Syndrome (people and cats): Issue: Obesity, Hyperglycemia (insulin resistance) Develop: Heart and Kidney Disease

Balanced solutes (sodium) Renal handling General Scheme

65% reabsorption in proximal tubule Without regard to body need

Rest of reabsorption is more distal in nephron Most is with regard to body need

Typically, about 99% of filtered load is reabsorbed but it varies according to body needs

Hormonal influence on sodium reabsorption Aldosterone enhances distal tubule reabsorption

Location Na+ H2O

Proximal tubule 65% 66%

Loop of Henle 25% 15%

Distal tubule 8% 4%

Total 98% 85%

Overall scheme for Renal Na Handling

Cortical nephrons Juxtamedullary nephrons Short loop of Henle Long loop of Henle Thin descending limb Thin descending limb Thick ascending limb Thin ascending limb

Thus, the juxtamedullary would be able to filter a larger amount of urine

Overall scheme for Renal Na Handling

Freely filtered Proximal reabsorption

multiple carriers 65% - no regard to body need

Thick Ascending Limb Distal tubule Collecting Duct

Note: There is an accumulation of NaCl and Urea in the interstitial fluid in the medulla of the kidney

Urea is a byproduct of protein metabolism produced by liver and some is mainteined in medulla but most is excreted in the urine

Na+ Factoids

Active Transport Proximal Distal Thick segment of ascending limb

Passive Diffusion Loop of Henle: the Na enters the cells, which then

expel it because of the Na/K pump (think SGLT-1/2 transporters)

Distal tubule and collecting duct

Na reabsorption (and K/H secretion) Adjusted in accordance with body needs Hormone-sensitive:

Aldosterone from adrenal cortex increases Na reabsorption (and K/H secretion)

Secretion

Secretion is often used for what we called Excreted Solutes Increases amount of substance that is excreted in urine Examples:

Urea (waste product of protein metabolism) Medications, such as antibiotics

pH of extracellular fluid (ECF) is tightly regulated

Enzyme systems function optimally within small pH ranges ECF pH normally 7.3 7.5 Diet and associated metabolic processes alter H+ production

Meat proteins: increase H+ generation Plant proteins: herbivores (horses, cows) and vegetarians; less H+

Defense of acid-base homeostasis is achieved by 3 systems that act in concert (Immediate):

Buffers act as sponge to bind free H+ in ECF which minimize effects of H+ on pH (only free H+ contribute to pH)

Kidneys control bicarbonate, while respiratory controls carbon dioxide (Short-term = minutes):

Ventilation (respiratory system removes or retains CO2) (Long-term = hours to days):

Renal handling (reabsorption, excretion) of HCO3- and H+

Renal Contribution to Acid-Base Balance

Proximal tubule Bicarbonate reabsorption Carbonic anhydrase

enzyme present in cytosol and on brush border surface of tubular cells

Distal Tubule Proton secretion NH3 and Phosphate in

tubular fluid serve as buffers to absorb the H+

Proximal Distal Tubular Cell Tubular Cell

Tubular fluid Tubular fluid

Regardless of hydration, 2/3 of water will be reabsorbed at proximal tubule Little Xs are NaK2Cl Osmolarity of the fluid in interstitial fluid is 600 mo/L Urea is added as well, which increases osmolarity Waters move through aquaporins and channels

Kidney is responsible for: Conversion of Vitamin D to its active form Release of erythropoietin (stimulation of red blood cell production) Regulates blood pressure Regulates electrolyte levels Regulates acid-base balance