Advanced Human Physiology course

LS607

Module 7

Renal Physiology (1)

23 October 2023
Func%ons of the Kidneys

Ø Elimination of metabolic waste products:

Urea ß Amino acids
Creatinine ß Muscle creatine
Uric acid ß Nucleic acids
Bilirubin ß Hemoglobin

Ø Elimination of hormone metabolites, drugs and foreign chemicals.

Ø Regulation of water and electrolyte balance

Ø Regulation of arterial pressure: Renin-Angiotensin System

Ø Regulation of Acid-base balance

Ø Regulation of Erythrocyte production: Erythropoietin

Ø Regulation of Calcitrol (vitamin D)

Ø Glucose synthesis
The nephron– func%onal unit of the kidney - and renal microcircula%on

Afferent arteriole à a tuft of Glomerular capillaries (Glomerulus)

à Efferent arteriole à peritubular capillaries

Ø HydrostaIc pressure in glomerular capillaries = 60mmHg >>

FiltraIon
Ø Hydrostatic pressure in peritubular capillaries = 13mmHg >>
Reabsorption

Change in the resistance of afferent and efferent arterioles

HydrostaIc pressure
Urine forma%on
Glomerular capillary membrane
v Endothelium (fenestrated capillaries)
Nega%vely
v Basement membrane: collagen and proteoglycans
charged
v Podocytes : epithelial cells

• High filtration rate

• Impermeable to plasma proteins
Ø The glomerular filtration is based on the size and electrical charge of solutes.
Ø Negatively charged large molecules are filtered
less easily than positively charged molecules
of equal molecular size.

Autoimmune disorder

Loss of negaIve charge

on the basement membrane

Minimal change
Proteinuria
nephropathy
Glomerular Filtra%on
Reabsorption
180 liters are 1 liter of urine
filtered per day

Ø Glomerular filtrate is composed of the same consItutes of

the protein-free plasma.

Ø Calcium and faYy acids which are bound to plasma proteins

are not filtered
20%
Glomerular Filtration Rate (GFR)

Net filtration pressure: Balance of hydrostatic and colloid

osmotic forces acting across the capillary membrane

Capillary filtration coefficient (Kf)

Determinants of Glomerular Filtra%on Rate (GFR)
Net filtration pressure

GFR = Kf x (PG-PB)-(pG+pB) PG pG
Kf - a measure of the product of the hydraulic conductivity
and surface area of the glomerular capillaries.

Kf = 12.5 ml/min/mmHg <-- 100 g of kidney weight

Kf of glomerulus > 400 Imes than other Issues in the body

PB pB = 0

Chronic hypertension
Diabetes ObstrucIon of the urinary
tract (e.g. Stones)
Basement membrane thickness
PB
Kf

GFR GFR
Effect of Glomerular Capillary Colloid Osmotic Pressure on GFR
Ø Glomerular Capillary Colloid Osmotic Pressure (pG) is
Decrease in
influenced by two factors:
renal blood flow
1) Arterial plasma colloid osmotic pressure

2) Filtration fraction of plasma

125
𝐺𝐹𝑅
𝑭𝒊𝒍𝒕𝒓𝒂𝒕𝒊𝒐𝒏 𝑭𝒓𝒂𝒄𝒕𝒊𝒐𝒏 = (20%)
𝑅𝑒𝑛𝑎𝑙 𝑝𝑙𝑎𝑠𝑚𝑎 𝑓𝑙𝑜𝑤
625
Increase in renal
blood flow
Glomerular Capillary Colloid
OsmoIc Pressure (pG) GFR

Ø Changes in renal blood flow can influence GFR independently of

changes in glomerular hydrostatic pressure (PG).
Changes in glomerular hydrosta%c pressure serve as the primary means for
physiological regula%on of GFR.

• Arterial pressure
• Afferent arteriolar resistance
• Efferent arteriolar resistance

PG

(Darcy’s Law)
Factors that can decrease the glomerular filtration rate
Renal Blood Flow

Ø Kidneys receive very high blood flow compared to other organs

22% of cardiac output à 0.4% of body weight

Ø Oxygen delivered to the kidneys exceeds their metabolic needs

Ø Most of oxygen consumed because of the active Na+ reabsorption

by the renal tubules

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𝑅𝑒𝑛𝑎𝑙 𝑏𝑙𝑜𝑜𝑑 𝑓𝑙𝑜𝑤 =
𝑇𝑜𝑡𝑎𝑙 𝑟𝑒𝑛𝑎𝑙 𝑣𝑎𝑠𝑐𝑢𝑙𝑎𝑟 𝑟𝑒𝑠𝑖𝑠𝑡𝑎𝑛𝑐𝑒

• Sympathetic stimulus
• Hormones
• Local control

interlobular arteries, afferent arterioles, efferent arteries

Vascular Resistance
Sympathetic and hormonal control of
glomerular filtration rate

• Brain ischemia
• Severe hemorrhage
Mild ac%va%on Strong activation

Sympathetic
nervous system

Renal arteriole diameter

Na and water
reabsorpIon Ø Efferent arterioles are highly sensitive to AngII
Renal blood flow
Ø Non-steroidal anti-inflammatory agents (aspirin)
GFR à prostaglandins à GFR

! Volume depleIon/ stress condiIons

Autoregula%on of GFR and renal blood flow

Func%on of blood flow

autoregula%on

kidneys Other tissues

Constant GFR • Constant O2 and nutrient delivery

• Constant waste removal

Absence of
autoregulation
GFR = 180 L/day Urine = 1.5 L/day
100 mmHg
ReabsorpIon = 178.5 L/day

125 mmHg GFR = 225 L/day Urine = 46.5 L/day

ReabsorpIon = 178.5 L/day
Tubuloglomerular feedback control of GFR and renal blood flow
(Juxtaglomerular apparatus)
Ø Sensing the changes in NaCl level in the distal tubules
Tubular reabsorption is large but highly selective

1%
Tubular reabsorp%on model : passive and ac%ve transport mechanisms

Main active transporters

in the kidneys :

• Na+/K+ ATPase Filtration

• H+ ATPase
• H+/K+ ATPase
• Ca2+ ATPase

Active Transport

Electrochemical gradients

Secondary AcIve Transport

Example: ac%ve transport of Na+ through the tubular epithelial cells

Keep the intracellular

Na+ level low
Transport maximum for substances that are actively reabsorbed

Diabetes
Proximal tubules

Proximal tubule epithelial cells:

• Large number of mitochondria
• Extensive Brush border

• Co-transporters
• Counter transporters

Ø SecreIon of toxins, drugs (aspirin)

and organic acids (bile salts,
oxalate, urate, and catecholamines)
Loop of Henle
Thin epithelial cells:
• No brush borders 20% water
• Few mitochondria reabsopIon

Descending loop: 20% water

Highly permeable to water diffusion

Ascending loop:
Impermeable to water

Ø Thick ascending loop

• Na+/2Cl-/K+ co-transporter uses
the electrochemical gradient
• Impermeable to water
Distal tubule and collecting tubule
Ø It contains “Macula Densa”
Dilu%ng segment:
• Impermeable to water
and urea
• Water permeability
controlled by ADH
• Reabsorbs most ions

Principal cells Hypertension

• Reabsorb Na+ Heart failure
• Secrete K+
Intercalated Cells
• Reabsorb or secrete K+, H+
and HCO3-
• Role in Acid-base regulaIon

• Potassium-sparing diureIcs
decrease the excreIon of K+ in
urine.
• CompeItor with Aldosterone
Medullary collecting duct
Medullary collec%ng ducts:

• Water permeability controlled by

ADH

• Permeable to urea via urea

Transporters

• Secrete loads of H+ à important

role in Acid-Base regulaIon

Type A Intercalated cells

• Secrete H+ and absorb HCO3- in

Acidosis

Type B Intercalated cells

• Reabsorb H+ and secrete HCO3-

in Alkalosis
Summary: tubular reabsorp%on phases for the major solutes

(PAH) = para-aminohippuric acid