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LECTURE 1: ANATOMY, BASICS OF URINE FORMATION

Function of the kidneys
Regulation of water, ion balance, pH
Removal of metabolic waste products from the blood
Removal of foreign chemicals from the blood
Production of hormones/enzymes
o Erythropoietin: erythrocyte production
o Renin: controls formation of angiotensin and influences Na
& BP
o 1,25 dihydoxyvitamin D: influences Ca balance
Anatomy
2 kidneys: 150 g each
locaed behind peritoneum on each each of vertebral column
against posterior abdominal wall
Renal cortex
Renal medulla
Renal pelvis
Blood circulation
Renal artery interlobar artery at border of medulla and
cortex= arcuate artery interlobular artery nephron
Renal vein
Nephron
Each kidney has 1 million nephrons
Each nephron consists of
o Renal corpuscle
Glomerulus (capillary loops)
Bowmans capsule
o Tubule
Nephron tubule anatomy
Proximal tubule (convoluted, straight)
Loop of henle (descending thin, ascending thin, ascending thick)
Distal convoluted tubule
Collecting duct system (cortical collecting duct, medullary
collecting duct)
Renal corpuscle
Bowmans space: initial urine is collected
Bowmans capsule
o visceral layer podocytes
epithelial cells: cell processes that loop like feet

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o Parietal layer
(outside)
Glomerular capillary wall
Endothelial cells with lots
of holes called fenestra
Basement membrane=
intracellular matrices
Visceral glomerular
epithelial cells
(podocytes)
Vascular supply of nephron
20% of blood is filtered
the rest of the blood continues out in the efferent arteriole and
branch into peritubular capillaries to supply kidney with blood
Three processes of urine formation
Glomerular filtration
Tubular secretion
Tubular reabsorption
Glomerular filtration
Plasma glomerular capillaries Bowmans space
Glomerular filtrate: fluid in bowmans space
o Cell-free
o Contain same substances/concentrations as plasma
Except proteins

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LECTURE 2: GLOMERULAR FILTRATION & TUBULAR

REABSORPTION/SECRETION & CONCEPT OF CLEARANCE
Not filtered by glomerular filtration
Cells
Proteins (albumin, globulin)
Protein bound substances
o Half of calcium ions, fatty acids
Forces involved in filtration
Favouring filtration
o Glomerular capillary blood pressure (60mmHg)
Opposing filtration
o Fluid pressure in Bowmans space (15 mmHg)
o Osmotic pressure due to protein in plasma (29mmHg)
Net= 16 mmHg favouring
Glomerular filtration rate (GRF)
GFR= volume of fluid filtered from glomeruli to Bowmans
space/time
Regulated by: net filtration pressure
o Membrane permeability
o SA available for filration
Normal GFR= 180 L/day
Regulation of GFR
To decrease: constrict AA or dilate EA
To increase: constrict EA or dilate AA

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Filtered load
Total amount of any freely
filtered substance
= GFR x plasma
concentration of substance
IF > amount excreted= net
reabsorption
IF < amount excreted= net
secretion
Reabsorption
Either paracellular or
transcellular
Not regulated: glucose, amino acids
Highly regulated: water, inorganic ions
2 mechanisms of reabsorption
Diffusion: across tight junctions connecting tubular epithelial
cells
o Paracellular eg// urea
Mediated transport: across tubular cells (transcellular)
o Usually coupled to the reabsorption of Na
Transport maximum
When transport proteins are saturated
Diabetes mellitus: HIGH glucose concentration, Tm exceeded,
glucose appears in the urine
o This is called glucosuria
Tubular secretion
Also mediated by diffusion and transcellular mediated transport
Most important secreted: hydrogen ion, potassium
Tubular secretion usually coupled to the reabsorption of Na
Division of labour in the tubules
Proximal tubule: reabsorbs filtered water, solutes
o Secretes solutes, except K
Henles loop: reabsorbs large quantities of ions (less water)
DCT/CD: fine tuning
o Most homeostatic controls exerted here
Concept of clearance

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Volme of plasma from which that substance is completely

removed by kidney/ time
Cs= (urine concentration of S) x (urine volume/time)/ (plasma
concentration of S)

Inulin clearance
Inulin= polysaccharide administered intravenously
Freely filtered but not reabsorbed, secreted or metabolized
Cin= GFR
Creatine clearance
Creatine= waste produc produced by muscle
Freely filtered at glomerulus and NOT reabsorbed or metabolized
o Small amount secreted at tubule
Creatinine clearance is used as a clinical marker of GFR
LECTURE 3: REGULATION OF NA BALANCE

Water and sodium balance

Water output=input=
0.4L-25L/day
Na output= Na input= 0.05-25g/day

Basic renal processes for Na and water

Freely filtered but almost NO secretion
o 99% reabsorbed
2/3 of reabsorption in proximal tubule
Hormonal control of reabsorption occurs in DCT and CD
Na= active process occurring in all segments
o Except descending thin limb of Henles loop
Water= by diffusion, dependent on Na reabsorption
Active sodium reabsorption (proximal tubule)

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On basolateral membrane
o Na/K ATPase pump Na OUT
Intracellular concentration of Na is low
On apical (luminal membrane)
o Na goes from tubular lumen to epithelial cells
Proximal tubule: Na/H anitporter and Na/glucose
cotransporter
CCD: diffusion via Na channel

What is sensing total body Na

Na is major extracellular solute
Total body Na sense by intravascular filling by baroreceptors in
cardiovascular system
Renal regulation of Na by GFR
Increase Na LOSS= decrease plasma volume= decrease BP
Direct effect= decrease GFR
OR= activate sympathetic= constrict aa= decrease GFR

Renal regulation of Na by reabsorption

Aldosterone: secreted by adrenal cortex
o Stimulates Na reabsorption in DCT and CCT
Renin= more aldosterone
o Stimulated by baroreceptors in juxtaglomerular apparatus
o Secreted by juxtaglomerular cells
ANP= atrial natriuretic peptide
o Secreted by cells in cardiac atria
o INHIBIT Na reabsorption and INCREAES GFR
o Stimulated by increases BP or increase in Na
LECTURE 4: REGULATION OF WATER BALANCE
Water reabsorption dep on Na reabsorption (proximal)
Na reabsorped from lumen to interstial fluid
Local osmolarity in lumen decreases
Different in osmolarity causes net diffusion of water to follow
o Via tubular cells membrane or tight junctions
From interstitial fluid: water and Na move by bulk flow into
peritubular capillaries

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Urine concentration: counter current multiplier system
Can concentrate urine up to 1400 mOsm/L
Concentration occurs in the medullary collecting ducts
o Depends on the hyperosmolarity of the interstitial fluid
o If vasopressin: water diffuses out into interstitial fluid and
carried away
Concurrent multiplier system
1. Ascending: actively reabsorbs NaCl but impermeable to water
2. Descending: Water diffuses out but impermeable to NaCl
3. New urine comes in
SO when it enters loop= 300mOsm, when it leaves= 100mOsm
Longer loop= higher osmolarity difference that can be achieved
Water permeability of tubules
Depends on tubular segment
o Proximal= highly permeable
Depends on presence of water channels (aquaporins) in
membrane
o In CCD and MCD: controlled vasopressin
Vasopressin
Peptide hormone (ADH)
Receptors: GPCR V1 (smooth muscle) and V2 (kidney)
Stimulars insertion of aquaporins in luminal membrane
o Vasopressin present= water reabsorption
o Vasopressin not present= water diuresis
Diabetes insipidus= vasopressin doesn't work
o Urine= 10-20 L/day
Regulation of vasopressin
Osmoreceptor (most important)
o Excess H2O= increase H2O concentration= decrease
activity of hypothalamic osmoreceptors= decrease
vasopressin secretion
Baroreceptor (less sensitive)
o Decrease plasma volume= decrease BP= increase
vasopressin
Thirst caused by
Baroreceptors (decrease in plasma volume)
o Angiotensin
Osmoreceptors (increase in osmolarity)

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Dry mouth, throat

STOPPED by metering of water intake by GI tract

LECTURE 5- K REGULATION, H REGULATION

K regulation
K= more abundant
intracellular ion
K concentration in
extracellular is important
for excitability
o Resting membrane
potential DEPENDS on
K concentration
Hyperkalemia: >5 mEq/L in extracellular
Kypokalemia: < 3.5 eEq/L in extracellular
Renal regulation of K
K is freely filtered
o Most is reabsorbed: 15-99% (usually 86%)
K can be secreted at the CCD
o Changes in K excretion due to changes in K secretion in
CCD
And some in DCT
o When Na is reabsorbed K is secreted because of Na/K
ATPase
K secretion regulated by
Dietary intake of K
Aldosterone
o Increase K intake increase blood K
Direct effect= increase K secretion
OR= increase aldosterone= increase K secretion
o Renin-aldosterone due to offer causes (decrease plasma
volume)
Hyperaldosteronism

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Adenoma of adrenal gland (benign)

Increase fluid volume, hypertension, hypokalemia, renin
suppressed, metabolic alkalosis

Hydorgen ion regulation

40nmol/L
CO2+ H2O H2CO3 HCO3+ H

Extrace
llular
pH=
7.4=

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Nonvolatile acids
Phosphoric acid
Sulfuric acid
Lactic acid
Avg net production= 40-80 mmol of H+/day
Buffer of hydrogen ion
Any substance that can reversibly bind H ions
Major extracellular buffer: CO2/HCO3 system
Major intracellular buffer: phosphates, proteins
DOES not eliminate hydrogen ions
Ultimate controls of hydrogen ion
Respiratory system (CO2)
Kidneys (HCO3)
Renal mechanisms of H control
Low H concentration= kidneys excrete HCO3
High H concentration= kidneys
produce new HCO3
Renal handling of HCO3
Normally: kidney reabsorb all filtered
HCO3 (unless alkalosis)
Also mediated by H/K ATPase and
Na/H antiporter
Addition of new HCO3 to plasma
Achieved in 2 ways
o H+ secretion and excretion on
nonbicarbonate buffers (phosphate)
Only happens after all HCO3 in lumen has been
reabsorbed
o Glutamine metabolism with NH4+ excretion
Mainly in proximal tubule
Also called H excretion bound to NH3

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LECTURE 6: H REGULATION & DIURETICS & KIDNEY DISEASES

Classification of acidosis and alkalosis
Low H concentration (high pH): alkalosis
o Respiratory alkalosis: hyperventilation (high altitude)
o Metabolic alkalosis: vomiting (loss of H)
High K concentration (low pH): acidosis
o Respiratory acidosis: respiratory failure with CO2 retention
o Metabolic acidosis: diarrhea (loss of HCO3)
Hyperaldosteronism: increase H secretion in DCT and CCD
Response to acidosis (high H concentration)
1. H is secreted to reabsorb all filtered HCO3
2. More H secreted= new HCO3 to plasma
a. H excreted bound to non HCO3 buffer
3. Tubular glutamine metabolism and ammonium exterion are
enhanced= new HCO3 to plasma
NET= More new HCO3, compensate for acidosis
o Urine is highly acidic (4.4)
Response to alkalosis
1. Rate of H secretion inadequet to reabsorb all filtered HCO3
a. HCO3 excreted in urine
2. Little H secretion
3. Tubular glutamine metabolism/ ammonium extretion decreased
a. Little new HCO3 in plasma
NET= plasma HCO3 decrease
o Urine is highly alkaline (>7.4)

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Diuretics
Drugs used to increase volume of urine
Act on tubules to inhibit reabsorption of sodium, ions
o Water excretion, ions increase
Loop diuretics: act on thick ascending limb of loop of Henle
o Inhibit cotransport of Na, Cl, and K
o Eg// furosemide
K sparing diuretics: inhibit Na reabsorption in CCD= inhibit K
secretion
o Plasma concentration of K does not decrease
o Either by clocking action of aldosterone or aldosterone
regulated epithelial Na channel in CCD
o Eg// amipride, spironoloactone
Clinical use of diuretics
Abnormal expansion of extracellular fluid (edema)
Eg// congestive heart failure
Eg// hypertension= high BP
Features of kidney disease/failure
Proteinuria
Accumulation of waste products in blood
High K concentration in blood
Metabolic acidosis
Anemia (decreased secretion of erythropoiten)
Decrease secretion of vitamin D= hypocalcemia
Treatment of kidney failure (90% of nephrons stop)
Hemodialysis
o Blood leaves arm filter back to arm
Peritoneal dialysis

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o Lining of patients abdominal cavity used as dialysis

membrane
o Fluid injected into cavity solutes diffuse into fluid from
persons blood fluid is exchanged serveral times/day
Kidney transplantation
o From deceased or living relative/unrelated donor
o Anti-rejection treatments improved organ shortage