Renal Physiology - Physiology

Functions of the Kidney

Regulation of fluid and electrolyte balance Regulation of plasma osmolarity Removal of metabolic wastes, toxins, drugs Endocrine functions (Renin & Erythropoietin) Metabolism Ensuring long-term acid-base balance

Two major classes of Nephrons

Cortical (superficial, located in cortex) - 80% Juxtamedullary (deep) - 20%

Renal corpuscle

Comprised of Glomerulus and Glomerular (Bowman's) capsule

Glomerular (Bowman's) Capsule

Consist of Capsular outer layer, visceral layer (podocytes), Bowman's space (separates two layers)

Filtration membrane

Fenestrated endothelium of glomerular capillaries, Basement membrane (negatively charged), and foot processes of podocytes (w/ filtration slits)

*No macromolecules, ONLY H2O, glucose, AAs, nitrogenous wasters, solutes smaller than plasma proteins pass (NO blood cells pass)

Glomerulus

specialized for filtration

afferent arteriole --> glomerulus --> efferent arteriole

Peritubular capillaries (cortical nephron)

Low-pressure capillaries adapted for absorption of H2O and solutes; cling to adjacent renal tubules in cortex

Vasa recta (Juxtamedullary nephron)

Long (thin-walled) vessels parallel to long nephron loops of juxtamedullary nephrons

Jutaglomerular Apparatus (JGA)

one per nephron Has three cell populations:

• Macula densa

• Granular cells

• Extraglomerular mesangial cells

Macula densa

Epithelial cells of DCT (near renal corpuscle) Function as chemoreceptors

Granular cells

Granules contain Renin Function as mechanoreceptors (sense blood press. in afferent arteriole)

Extraglomerular mesangial cells

B/w afferent & efferent arterioles May pass signals b/w macula densa & granular cells

Glomerular Filtration Rate (GFR)

Volume of plasma that is filtered across the glomerular per unit time

• The amt of filtrate kidneys produce each minute (average: 125 mL/min)

Two Major Forces of GFR

• Hydrostatic pressure (forces fluids & solutes thru filtration membrane)

• Oncotic pressure

Outward pressures promoting filtrate formation

Hydrostatic pressure in glomerular capillaries (HP (GC)) = glomerular blood pressure (55 mm Hg)

Inward forces stopping filtrate formation

1. Hydrostatic pressure capsular space (HP (BS)) - 15 mmHg

2. Colloid oncotic pressure in capillaries (OP (GC)) - 30 mmHg

Net Filtration Pressure (NFP)

Sum of forces, pressure responsible for filtrate formation Main factor controlling glomerular filtration rate

Net Filtration Pressure Equation

NFP = (HPgc - HPbs) - (onocGC - onocBS) NFP = outward pressures - inward pressures NFP = (55 - 15) - (30 - 0) = 40 - 30 = 10 mm Hg (onocBS is negligible)

GFR is directly proportional to...

1. NFP

2. Total surface area available for filtration

3. Filtration membrane permeability

Mechanisms of Urine Formation

Three renal processes: Tubular absorption Tubular secretion Glomerular filtration

Renal Clearance

Cx = Ux * V/ Px

Cx = C inulin

Filtered, but not Reabsorbed or Secreted

Cx < C inulin

Filtered and Reasbored Ex: Na+, Cl-, HCO3-, phosphate, urea, glucose, and amino acids

Cx > C inulin

Filtered and Secreted Ex: para-aminohippuric acid (PAH), creatinine, urea, NH4+, and morphine

Cx < or > C inulin

Filtered, Reabsorbed and Secreted Ex: H+ and HCO3-

Renal Plasma Flow (RPF)

RBF - (1 - HCT)

Normal adult male: RBF = ~1L/min, HCT = ~40% Ex: Renal Handling of PAH (effective RPF)

Constriction of Afferent arteriole

Decrease RPF Decrease HP (Glomerular Cap) --> Decrease GFR

Constriction of Efferent arteriole

Decrease RPF Increase HP (Glomerular Cap) --> Increase GFR

Control of GFR

1. Autoregulation (local level) intrinsic

2. Hormonal regulation (by kidneys)

3. Autonomic regulation (sympathetic division)

Renal autoregulation

Two types:

1. Myogenic mechanism

2. Tubuloglomerular feedback mechanism

Countercurrent multiplier

interaction of filtrate flow in descending/ascending limbs of nephron loops of juxtamedullary nephrons --> creates gradient

Countercurrent exchanger

blood flow in descending/ascending limbs of vasa recta --> maintains gradient

Thin descending limb

Permeable to water, impermeable to solutes

Thick ascending limb

Impermeable to water

Medullary osmotic gradient

Concentration gradient created in peritubular fluid of medulla

• Na+, K+, 2 Cl- moves out of ascending limb (via Na+-K+/2Cl- transporter) into interstital fluid and then water diffuses out of descending limb --> raising osmolality of intersititial fluid (to max 1200 mL/min)

Vasa recta - Countercurrent exhcanger

• Highly permeable to water and solutes

a. Descending limb: water out, NaCl in --> at bottom of loop reaches 1200

b. Ascending limb: water in, NaCl out --> ends @ 325 (slightly higher than 300 start)

Urea Recycling

Cortical and outer medullary collecting ducts: ADH increases water permeability but NOT urea permeability --> water is absorbed but urea remains --> urea increase

Inner medullary collecting ducts: ADH increases water permeability & facilitated diffusion of urea (UT1) --> helps maintain gradient

Anitidiuretic hormone (ADH)

Prevents excessive water loss in the urine and increases water absorption

*Targets kidney's collecting ducts

Aldosterone

Determines rate of Na+ reabsorption and K+ loss in kidneys

• secreted in response to rising K+ or falling Na+

Atrial natriuretic peptide (ANP)

Released by atrial cells in heart due to stretch (inc BP)

• Effects: Decreases in blood pressure and volume a. Decreased ADH, renin and aldosterone production b. Inc excretion of Na+ and H2O c. Promotes vasodilation directly and dec of angiotensin II

Alkalosis

arterial pH > 7.45

Acidosis

arterial pH < 7.35

Net gain of H+

Hyperventilation (Increase in CO2, slow breathing) Diarrhea (loss of HCO3-) Cell and protein metabolism Ingestion of acid containing food

Net loss of H+

Hyperventilation (decrease in CO2) Vomiting Urinary acid excretion

HH equation

pH = Kidney / Lung = [HCO3-] / P(CO2)

Blood pH rises (alkaline)

Bicarbonate ions are excreted --> H+ ions retained by kidney tubules

Blood pH falls (acidic)

Bicarbonate ions are reabsorbed --> H+ ions are secreted

Respiratory acidosis w/ renal compensation

Indicated by: LOW pH HIGH P(CO2) (= cause of acidosis) and bicarbonate levels (compensation)

Kidneys reabsorb more bicarbonate --> create new bicarbonate and secrete more H+

Respiratory alkalosis w/ renal compensation

Indicated by: HIGH pH LOW P(CO2) Decreasing HCO3- levels

Two mechanisms to generate bicarbonate ions

1. Excretion of buffered H+

2. Excretion of NH4+ (glutamine)