Section 5: Renal Physiology

renal function

kidney excretion of metabolic waste products and foreign chemicals; hormone secretion & metabolism; gluconeogenesis; regulation of arterial BP; water & electrolyte balance

renal blood circulation

20% of CO → renal arteries → interlobar arteries → arcuate arteries → cortical arteries → afferent arteries → glomerular capillaries → efferent arteries → cortical peritubular capillaries/vasa recta → venules & veins

nephron

functional unit of the kidney; 80% are cortical & 20% are juxtamedullary

cortical nephron

80% of nephrons; short loop of Henle & glomerulus closer to outer cortex

juxtamedullary nephron

20% of nephrons; longer loop of Henle & glomerulus closer to medulla

flow of urine thru nephrons

renal corpuscle → prox. tubule → thin descending loop of Henle → thin & thick ascending loop of Henle → distal tubule → cortical and medullary collecting tubules

renal corpuscle

glomerulus + bowman’s capsule = glomerular filtration system

juxtaglomerular apparatus/complex

macula densa & juxtaglomerular cells that regulate the function of each nephron

macula densa

specialized epithelial cells in distal convoluted tubule with chemoreceptors for [Na⁺]; part of the juxtaglomerular apparatus

juxtaglomerular cells

secrete renin for angiotensin; part of the juxtaglomerular apparatus

HP_B

bowman’s capsule hydrostatic pressure; influenced by GFR, tubular obstruction, and urinary tract obstruction

P_G

glomerular hydrostatic pressure = 55-60 mmHg; drives glomerular filtration/secretion into tubules; influenced by arterial BP & afferent and efferent arteriole R

π_G

glomerular capillary oncotic pressure; influenced by FF and π_A

FF

filtration fraction = GFR / RPF = 0.2 = 20% of plasma filtered; incr. π_G

π_A

arterial plasma oncotic pressure; incr. π_G

proximal tubule

bulk reabsorption site permeable to ions, glucose, H₂O; 80% filtered HCO₃^-

uses Na⁺/H⁺ antiporters, Na⁺/K⁺ ATPase pump, insulin-independent SGLT, Na⁺-K⁺-2Cl^- cotransporters, and PTH

thin descending loop of Henle

reabsorption of H₂O; impermeable to solutes

thick ascending loop of Henle

reabsorption of solutes Na⁺, Cl^-, K⁺, HCO₃^-, Ca²⁺, Mg²⁺

secretion of H⁺

early distal tubule

reabsorption of 5% filtered NaCl; impermeable to H₂O and urea

late distal tubules & collecting tubules

ADH & aldosterone reabsorption of 5% filtered HCO₃^-, H₂O, Na⁺; impermeable to urea

secretion of H⁺ (intercalated cells), K⁺ (principal cells)

excretion

excretion/GFR = filtration - reabsorption + secretion

GFR

glomerular filtration rate = 125 mL/min = 180 L/day; non-selective substances leave plasma thru 3 filtration barriers → tubule lumen in renal corpuscle

The entire plasma volume gets filtered ___x per day.

60

3 filtration barriers for GFR

1. glomerular capillary endothelium

2. basal lamina

3. epithelium of Bowman’s capsule

reabsorption

substances taken back into blood capillaries

secretion

excretion of substances into renal tubules to be urinated out

GFR determinants

RBF, renal BP, filtration coefficient, NFP

RBF

renal blood flow; pressure difference b/n renal artery and vein / total renal R

___ afferent arteriole R → decr. HP_G → ___ GFR

incr.; decr.

___ efferent arteriole R → incr. HP_G → ___ GFR

incr.; incr.

k_f

filtration coefficient = hydraulic conductivity * SA = 12.5 mL/min/mmHg

_these conditions_ → decr. k_f → ___ GFR

chronic HTN, obesity/DM, glomerulonephritis; decr.

NFP

net filtration pressure = P_G - HP_B - π_G = 10 mmHg; favors secretion into tubules

Cl_R

renal clearance = V_plasma cleared / minute = (rates of filtration + secretion - reabsorption) / plasma [drug]; rate at which substances are removed/cleared from the plasma; used to assess kidney function

renal clearance ratio

Cl_R of drug / Cl_R of creatinine

Cl_R of glucose

= 0% → total reabsorption

Cl_R of creatinine

= 100% → total excretion as a waste product in urine

myogenic mechanism

autoregulation of GFR mechanism using Laplace’s law (T = p * r); incr. arterial BP → Ca²⁺ influx → incr. vascular R → decr. GFR

mascula densa/tubuloglomerular feedback

autoregulation of GFR mechanism; incr. macula densa flow → afferent arteriole constrict. → incr. afferent arteriole R → decr. HP_G → decr. GFR

angiotensin II feedback

autoregulation of GFR mechanism; low macula densa [NaCl] sensed → incr. renin → incr. angiotensin II → incr. efferent arteriole R → incr. HP_G → incr. GFR

[Solute] in different parts of the tubule depend on ___ of solutes & water.

reabsorption

high [solute] in urine

H₂O reabsorption > solute reabsorption

low [solute] in urine

H₂O reabsorption < solute reabsorption

RAAS

renin-angiotensin-aldosterone system; regulates BV & systemic vascular R → influences CO & arterial BP

↑ ß₁ & ↓ BP, BV → ↑ renin → ↑ angiotensin II → ↑ aldosterone vasoconstriction → ↑ Na⁺ reabsorption in proximal tubule, loop, distal tubules, collecting tubule

aldosterone regulators

stimulators: incr. angiotensin, K+, ACTH

inhibitors: incr. Na+, atrial natriuretic factor (ANF)

responses to Na⁺ intake

incr. Na⁺ excretion, GFR; decr. Na⁺ reabsorption

loop of Henle countercurrent multiplier system

NaCl reabsorption and countercurrent flow throughout the thick ascending limb to concentrate & dilute urine in tubules; influenced by ADH

acid-base buffer systems

maintain acid-base balance by releasing H⁺ when pH is high and accepting H⁺ when pH is low

acid

molecule that releases H⁺ in solution

ex: lactic acid

base

molecule that accepts H⁺ in solution

ex: bicarbonate (HCO₃^-)

intracellular buffers

proteins, PO₄^2- groups, HCO₃^-

extracellular buffers

HCO₃^-, Hb, blood proteins

HCO₃^- buffer

bicarbonate; major ECF buffer/base for accepting H⁺; typically reabsorbed in prox. tubule (80%), thick asc. limb (15%), and collecting duct (5%)

bicarbonate buffer system

HCO₃^- + H⁺ ←→ H₂CO₃ ←→ CO₂ + H₂O

carbonic acid dissociation

CO₂ + H₂O ←→ H₂CO₃ ←→ H⁺ + HCO₃^-

pH

pH = pKa + log₁₀(HCO₃^- / H₂CO₃)

norm pH = 7.35-7.45

survival pH range = 6.8-7.8

respiratory influences on acid-base balance

1. incr. [H⁺] → decr. pH = more acidic

2. carbonic acid dissociation shifts L toward CO₂ + H₂O

3. CO₂ expiration → incr. pH = more alkaline

   1. incr. blood PCO2 → decr. pH and vice versa

renal regulation of acid-base balance

decr. blood pH → decr. rate of HCO₃^- excretion and vice versa

H⁺ during exercise ___ enzymes in ATP production and muscle contractile process

inhibits

sources: volatile acids, fixed acids, organic acids

volatile acids

source of H⁺ during exercise

ex: CO₂ from carb, fat, protein metabolism

fixed acids

source of H⁺ during exercise

sulfuric acid from AA metabolism; phosphoric acid from phospholipid & nucleic acid metabolism

organic acids

source of H⁺ during exercise

lactic acid & acetoacetic acid from carb, fat metabolism & exercise

acid-base balance regulators during exercise

lactic acid/intensity, blood & muscle pH, lactic acid buffering in muscle & blood

Incr. lactic acid production → ___ blood & muscle pH

decr. = more acidic

___ of buffering of lactic acid in the muscle happens…

1. 60%; thru intracellular proteins

2. 20-30%; by muscle HCO₃^-

3. 10-20%; from intracellular PO₄^2- groups

Buffering of lactic acid in the blood mainly utilizes ___ buffer.

HCO₃^-

The 1st line of defense against exercise-produced H+ is ___ ___ ___ of the intracellular compartment & blood, which act ___ to convert strong acids into weak acids.

chemical buffer systems; rapidly

The 2nd line of defense against pH shift during exercise is ___ ___ for metabolic ___.

respiratory compensation; acidosis

Intracellular buffering occurs with the aid of ___ ___, ___, and ___ ___.

cellular proteins; HCO₃^-; PO₄^2- groups