PHYSIO FINAL: Renal

What are the general functions of the kidneys?

• Excretion of metabolic wastes

• Regulation of blood volume and blood pressure

• Regulate blood electrolytes

• Acid-base balance

• Produce hormones

What do the kidneys excrete as metabolic waste?

Urea, Uric Acid, Creatine

Why are the kidneys important in long term blood pressure?

• Regulate blood volume and blood pressure

• Renin → Increases blood pressure

What blood electrolytes do kidneys regulate?

• Na+

• K+

• Ca++

Na+ levels in blood

Major ion determining ECF osmolarity and blood volume

K+ levels in blood

Cardiac, muscle, nerve function

Ca++ levels in blood

Muscle contraction, blood clotting, etc.

What substances do kidneys regulate for acid-base balance?

• H+ and HCO3-

• Plays significant role in pH homeostasis

What hormones do kidneys produce?

• Erythropoietin

• Renin

• Calcitriol

Erythropoietin

RBC synthesis

Renin

Na+ and BP regulation

Calcitriol

• Active form of vitamin D

• Required for intestinal calcium absorption

Macroscopic parts of kidneys

• Renal Cortex

• Renal Medulla

• Renal Artery

• Renal Vein

Renal Cortex

Outer layer

Renal Medulla

Inner layer

Renal Artery

Brings oxygenated blood from heart to kidney

Renal Vein

Brings deoxygenated blood from kidney to heart

Microscopic structures of kidneys

Nephrons

• Tubules that make urine

• Inside tubules = urine

What are the components of urine?

• 95% H2O

• 5% Solutes

  • Urea

  • Na+

  • K+

  • Phosphate

  • Sulfate

  • Creatinine

  • Uric Acid

What are the parts of a nephron?

• Renal Corpuscle

• Proximal Convoluted Tubule

• Loop of Henle/Nephron Loop

  • Ascending/Descending Limb

• Distal Convoluted Tubule

• Collecting Duct

BE ABLE TO LABEL!

Collecting ducts

Collect urine from many different nephrons

What are the components of the renal corpuscle?

• Glomerular/Bowman’s Capsule

• Glomerulus

Glomerular/Bowman’s Capsule

• Surrounds glomerulus

• Leaky/Porous

• Two layers = Parietal and Visceral

Glomerulus

• Capillaries composed of fenestrated endothelium → highly porous

• Filters blood

• Enters through afferent arteriole, exits through efferent arteriole

What are the two classes of nephrons?

• Cortical Nephrons

• Juxtamedullary Nephrons

Cortical Nephrons

• Sits in the cortex

• Make up majority of nephrons, 80-85% of nephrons

• Almost entirely in cortex

Juxtamedullary nephrons

• Make up about 15-20% of nephrons

• Long nephron loop deeply invade medulla

How are renal nerves supplied?

Sympathetic fibers from renal plexus

Order of blood flow in renal cycle

• Aorta

• Renal artery

• Afferent arteriole

• Glomerulus

• Efferent arteriole

• Peritubular capillaries

• Renal veins

• Inferior vena cava

What is the blood supply to the glomerulus?

• Specialized for filtration

• Afferent and efferent arterioles

• Efferent is smaller in diameter → Glomerular BP is higher

Peritubular Capillaries

• Specialized for reabsorption

• Empty into venules

• Surround PCT and DCT in cortical nephrons

Vasa recta

• Surround Loop of Henle in juxtamedullary nephrons

• Function in formation of concentrated urine

What are the three major renal processes?

• Glomerular filtration

• Tubular reabsorption

• Tubular secretion

Glomerular filtration

• PASSIVE

• Produces cell and protein-free filtrate

• Waste and electrolytes is removed from blood in glomerulus, will reabsorb some back later

• Is able to occur because of high BP in glomerulus (afferent>efferent diameter)

Tubular reabsorption

Selectively returns 99% of substances from filtrate to blood in renal tubules and collecting ducts

Tubular secretion

Selectively moves substances from blood to filtrate in renal tubules and collecting ducts

The terms “reabsorption” and “absorption” are in reference to what?

The blood/plasma levels

Reabsorption

Taken back into the blood from the filtrate

Secretion

Excreted from blood to filtrate

What is the fluid called once it enters Bowman’s capsule?

Filtrate

What does filtrate contain?

• Water

• Electrolytes

• Vitamins

• Amino acids

• Hormones

• Glucose

• Nitrogenous

• Waste

  • No proteins or blood cells

  • ~300 mOsm

What is GFR?

• Glomerular Filtration Rate

• Measures the amount of blood passing through glomeruli in kidneys per minute

Why does GFR need to be regulated?

• Maintain homeostasis of body fluids

• Blood pressure

• Waste excretion

What happens if GFR is too high?

• Generally positive

• Can indicate early, hyper-filtration stages of kidney disease

• High protein intake

• Pregnancy

• Can lead to leg swelling, high BP , fluid in lungs, pulmonary edema

  • Urine appears pale, straw-colored or light yellow

What happens if GFR is too low?

• Kidneys are not filtering properly

• Often signaling chronic kidney disease, acute kidney injury, significant damage to the kidneys

  • Urine looks foamy/bubbly, like scrambled eggs or beer foam due to high protein levels

How do changes in MAP affect GFR within normal ranges?

• Due to Renal Autoregulation, MAP has very little effect on GFR within normal ranges

  • Keeps renal blood flow and GFR constant despite fluctuating systemic blood pressure

EXTREME CASES: MAP directly influences GFR by determining renal blood flow and pressure

How does GFR influence MAP?

• If GFR is too high: Needed substances are not reabsorbed and are excreted in urine → decreased blood pressure

• If GFR is too low: Nearly all the filtrate, including waste products which need to be excreted, are reabsorbed → increased blood pressure

Intrinsic Controls

(Renal autoregulation, Direct mechanism)

• Myogenic mechanism

• Tubuloglomerular feedback mechanism

Myogenic Regulation (Increased MAP)

• Afferent arteriole dilates initially

• GFR increases initially

• Afferent arterioles constrict

• Restricts blood flow into glomerulus (decreased GFR)

  • Protects glomeruli from damaging high BP

Myogenic Regulation (Decreased MAP)

• Afferent constricts initially

• GFR decrease initially

• Afferent arterioles dilate

• Increased blood flow into glomerulus (increased GFR)

Without any regulation, how would MAP change GFR?

• Increase in MAP would lead to increased GFR

• Decrease in MAP would lead to decreased GFR

What are extrinsic controls?

• Override intrinsic controls

• Indirectly regulate GFR by regulating blood pressure (indirect mechanism)

  • Neural mechanisms

  • Hormonal mechanisms

Neural Mechanisms

• At rest under normal conditions (renal autoregulation mechanisms prevail)

• Low ECF volume/Low BP":

  • NE is released by SNS

  • Systematic vasoconstriction, which increases MAP

  • Blood volume and pressure increases

  • Increased GFR

  • No autoregulatory mechanisms kick in

Hormonal Controls

• Renin-angiotensin mechanism → maintains systemic blood pressure → increased GFR

What causes renin to be released?

• Reduced stretch of afferent arteriole (indicates low MAP and low GFR)

• Decreased NaCl concentration of filtrate in ascending limb of Loop of Henle (indicates GFR is too low)

• Sympathetic stimulation

Major differences between Intrinsic and Extrinsic Mechanisms?

Intrinsic:

• Directly regulate GFR

• Maintain GFR despite changes in MAP

• Operate under normal MAP

Extrinsic:

• Indirectly regulates GFR

• Maintains systemic blood pressure

• Operates when MAP is out of normal range

Increased MAP leads to?

Increased GFR

Decreased MAP leads to?

Decreased GFR

Increased GFR leads to?

• Too little reabsorption

• Decreased MAP

Decreased GFR leads to?

• Too much reabsorption

• Increased MAP

Tubular Reabsorption

Selectively returns 99% of substances from filtrate to blood in renal tubules and collecting ducts

Is tubular reabsorption passive, active or both?

Both active and passive transport of filtered material from nephron/tubule lumen into blood

What is the purpose of tubular reabsorption?

Reclaim substances the body needs

Where does most tubular reabsorption occur?

• PCT (Most here)

• Loop of Henle

• DCT and collecting tubules

Where is the Na+K+ pump and what does it assist in?

• The basolateral membrane

• Pumps out Na+ for Na+ reabsorption in the peritubular capillary

How does K+ get into the ECF and where does it go after?

• Leaks into ECF

• Some comes back in through pump, some goes to plasma and is reabsorbed

What part of the PCT cell does Na+ enter at?

The apical membrane

What type of transport do glucose, vitamins and AA’s use to get into the PCT cell?

2 coupled active transport (cotransport) symport proteins

What type of transport do glucose, vitamins and AA’s use to get reabsorbed by plasma?

Passive transport on basolateral membrane allows them to leave PCTget reabsorbed into plasma

What is reabsorbed by the PCT?

• Water → aquaporins

• Other ions and urea → tight junctions

• Lipid-soluble substances go directly through the bilayer

• HCO3-: Complicated mechanism

Co-transport

• Exhibit a transport maximum

• Na-glucose transporter can reabsorb all glucose as long as blood glucose does not exceed 200 mg/dL

• Vitamins and AA can be transported as well

Diabetes mellitus

Too much glucose in body → glucose in urine

Reabsorption of HCO3- in PCT

• Important in acid-base balance

• Increased HCO3- reabsorption leads to increased H+ secretion (loss of H+ from blood) → increased body pH

What reabsorption occurs at the Loop of Henle?

• Descending limb: Water can leave, solutes (NaCl) cannot

• Ascending limb: Water cannot leave, solutes (NaCl) can

Descending limb

• Permeable to water

• Not permeable to salt

Ascending limb

• Impermeable to water

• Pumps out salt

Osmolarity

Concentration of all solutes/Volume of solvent

How can I change osmolarity?

• Change concentration of solutes

• Change volume of solvent

Why does water move out via osmosis in the Loop of Henle?

Osmotic gradient in the interstitial fluid of the medulla

Which osmolarity is lower in descending limb and IF?

• Filtrate osmolarity is lower than IF

• Need to reach equilibrium, water leaves filtrate and enters IF

• Water is reabsorbed by plasma

• Filtrate osmolarity increases as it goes down the limn

  • Becomes more concentrated as it goes down Loop of Henle

Which osmolarity is lower in the ascending limb and IF?

• Filtrate osmolarity is higher than IF

• Need to achieve equilibrium, NaCl leaves filtrate and enters IF

• NaCl is reabsorbed by plasma

• Filtrate osmolarity decreases as it goes up the limn

  • NaCl continues leaving as you go up, filtrate continues becoming less concentrated