The Renal
Function
Anatomy
 The
kidneys are a pair of
fist-sized organs that are
located on either side of
the spinal column.
A
kidney consists of an
outer layer (renal cortex)
and an inner region
(renal medulla).
 The
functional unit of the
kidney is the nephron.
2
Nephron
 Structural
and functional unit of the
kidney
 1 million nephrons per kidney
 Consists of 2 parts
1.
Glomerulus (filtering system)
 tuft
of capillaries surrounded by Bowman’s
capsule
2.
3
Tubules
Nephron
Afferent arteriole
Glomerulus
Proximal tubule
Distal tubule
Bowman’s capsule
Collecting duct
Renal artery
Henle’s Loop
4
Nephron - Bowman’s capsule




5
Bowman’s capsule: funnel
with tubules as stem
Blood carried to
glomerulus by afferent
arteriole
Afferent arteriole divides to
form capillary network.
These capillaries reunite to
form efferent arteriole,
which carries blood out of
the glomerulus
Nephron - Bowman’s capsule

Blood filtered in glomerulus; some water
and small molecules removed

Size cutoff value of approximately 66,000 Da,
about the molecular size of albumin.
Glomerular filtrate collected in Bowman’s
capsule and enters tubules.
 Specific reabsorption occurs in tubules.


6
Most water and soluble nutrients reabsorbed
Tubule System

Proximal convoluted tubule



Loop of Henle



composed of the thin descending limb, which
spans the medulla, and the ascending limb,
which is located in both the medulla and the
cortex,
More water reabsorbed
Distal convoluted tubule


7
located in the cortex
Reabsorption of Glucose,
water, amino acids, Na, Cl & others
located in the cortex
Sodium and hydrogen ion reabsorption
Tubule System

The collecting duct

formed by two or more distal convoluted
tubules as they pass back down through the
cortex and the medulla to collect the urine that
drains from each nephron.
collecting tubules, then ureters → bladder
→ urethra
 1000 liter of blood through
glomerulus per day; 100
liters of glomerular filtrate
formed; 1 liter of urine
produced

8
Functions of Kidney
 Urine
formation
 Regulate body fluid, osmolality and
volume
 Regulate electrolyte balance
 Regulate acid-base balance
 Excrete waste products and foreign
substances
 Produce and excrete hormones
9
Urine Formation
Removal of potentially toxic waste products
 3 processes involved


Filtration, Reabsorption, Secretion
• Substance A is filtered and secreted, but not reabsorbed;
• Substance B is filtered and a portion reabsorbed
• Substance C is filtered and completely reabsorbed
10
Glomerular Filtration
 Glomerular
filtration rate (GFR) is
approximately 130 mL/min
 Cells and large plasma proteins
unable to pass through the
semipermeable membrane
 Glomerular filtrate is essentially
plasma without proteins.

11
water, electrolytes, glucose, amino acids, low-molecularweight proteins, urea, and creatinine, pass freely through
the basement membrane and enter the proximal
convoluted tubule
Proximal Convoluted Tubules
The next part of the nephron to receive
filtrate
 This filtrate contains




One function of the PCT is to return the bulk
of each valuable substance back to the
blood circulation.


12
waste products,
and substances that are valuable to the body.
Glucose, water, amino acids, Na, Cl & others
Organic acids and bases, hydrogen ions
and ammonia may be secreted into the
tubular fluid
Proximal Convoluted Tubules
 Reabsorption
passive

may be active or
Active — against a concentration
gradient (glucose, amino acids, low mw
proteins, sodium, etc.) —
 regulated
by kidney according to levels of
these substances in the blood

Passive — no energy involved — water
and urea
 Tubular
secretion may also be passive
or active
13
Loop of Henle
 Descending
limb is highly permeable
to water
 Passive reabsorption of water in
descending loop
 Ascending loop is impermeable to
water but actively reabsorbs sodium
and chloride
 it lowers the salt concentration
14
Distal Convoluted tubule
The function is to effect small adjustments
to achieve electrolyte and acid-base
homeostasis
 Small amount of sodium, chloride, water
are reabsorbed
 Under influence of AVP (ADH) increase
water permeability of tubule
(reabsorbs water)
 Potassium also reabsorbed or secreted


15
Aldosterone - sodium reabsorption and
potassium secretion
Collecting Duct
 The
collecting ducts are the final site
for either:


concentrating
or diluting urine
 Also
under control of ADH &
aldosterone

16
Reabsorption of water, sodium and
chloride
Regulation of Fluid and Electrolyte
Balance
 Water:


body water (weight) remains constant day to
day — ability of kidney to excrete or conserve
water
Water balance is controlled by voluntary intake
(thirst) and urinary loss
 Sodium:


17
freely filtered through the glomerulus and
reabsorbed by tubules
Active reabsorption of Na+ results in passive
transport of Cl- and bicarbonate and passive
reabsorption of water.
Regulation of Fluid and Electrolyte
Balance
 Potassium:
 Both the distal convoluted tubule and the
collecting ducts can reabsorb and excrete
potassium, and this excretion is controlled by
aldosterone
 Chloride:
 parallels sodium
 but reabsorption is passive in proximal tubules
 and active in distal tubules and collecting duct
18
19
Acid-Base Balance

Secretion of hydrogen ions from tubular
cells

Hydrogen ions generated in proximal and distal
tubules as a result of carbonic acid
H2O+CO2 → H2CO3 → H + HCO3-




20
React with bicarbonate ions
React with buffers — phosphate ions
React with ammonia (deamination of
gluatamine) to form ammonium ion
Excretion as free hydrogen ions
Nitrogenous Waste Excretion
 When
low GFR, levels of nitrogenous
wastes increase in blood — NPN’s



21
Urea
Creatinine
Uric Acid
Primary Endocrine Functions
 Kidneys
synthesize renin,
prostaglandins and erythropoietin
 Renin:


22
Renin is the initial member of the reninangiotensin-aldosterone system
help regulate sodium and potassium in
the blood, fluid levels in the body, and
blood pressure.
Primary Endocrine Functions
 Prostaglandins




23
A group of potent cyclic fatty acids
Behave like hormones
Prostaglandins produced by the kidney
increase renal blood flow, sodium &
water excretion
They oppose renal vasoconstriction due
to angiotensin
Primary Endocrine Functions

Erythropoietin





24
It is a single chain polypeptide.
It is produced by cells close to the proximal
tubules.
Its production is regulated by blood oxygen
levels "hypoxia increases its production".
Erythropoietin acts on the erythroid progenitor
cells in the bone marrow, causing their
maturation and increasing the number of RBCs.
In chronic renal insufficiency, erythropoietin
production is significantly reduced causing
anemia.
Secondary Endocrine Functions
The kidneys are the target locus for the
action of aldosterone
 For the catabolism of insulin, glucagon
and aldosterone
 The point of activation for vitamin D

25
Renal Disorders
 Acute
Glomerulonephritis
 Nephrotic Syndrome
 Tubular Diseases
 Urinary Tract Infection
 Acute Renal Failure
26
Acute Glomerulonephritis
 Acute
inflammation of the glomeruli
 Results in oliguria, hematuria, increased
BUN and serum creatinine, decreased
GFR and hypertension
 Red cell cast finding are of great
importance
 Proteinuria also present
Red cell cast
27
Nephrotic Syndrome
 Massive
proteinuria, edema,
hypoalbuminemia, hyperlipidemia,
and lipiduria
 Has many cuases
 Characterized by increased
glomerular membrane permeability —
loss of protein (greater than 2-3 grams
per day)
28
29
Tubular Diseases
 Depressed
secretion or reabsorption
of specific biochemicals
 Or Impairment of urine dilution and
concentration mechanisms
 Renal Tubular Acidosis — most
important
 Low values of phosphorus in serum,
and presence of glucose and amino
acids in urine
30
Urinary Tract Infection






31
Bladder — cystitis
Kidneys — pyelonephritis
Bacterial concentrations >100,000
colonies/mL is considered
diagnostic for infection
Increased number of white blood
cells
Increased number of red blood
cells may be present
White blood cell casts is
considered diagnostic of
pyelonephritis
Acute Renal Failure
Defined as occurring when the GFR is
reduced to less than 10 mL/minute.
 Prerenal — before blood reaches the
kidney




Renal — occuring in kidney



Acute tubular necrosis
Glomerulonephritis
Postrenal — after urine leaves kidney

32
Hypovolemia
Cardiovascular failure
Obstruction
 Usually
accompanied by oliguria
 Associated with varying degrees of
proteinuria, hematuria, and
presence of red cell casts and other
casts
 BUN and creatinine increase rapidly
 Can progress to chronic renal
insufficiency or failure
33
34
Renal Calculi

35
Renal calculi, or
kidney stones, are
formed by the
combination of
various crystallized
substances. Of
these, calcium
oxalate stones are
by far the most
commonly
encountered
Renal Function Tests


Tests of Glomerular Function

Creatinine Clearance

Most sensitive method of assessing renal function
Tests of Tubular Function


Non-protein nitrogen compounds




Urea nitrogen
Creatinine
Uric acid
Urinalysis and Microscopy

36
Concentration — Dilution Studies
pH, Chemical Analyses (glucose, protein,
bilirubin/urobilinogen & others)
Renal Function Tests

Cystatin C is a low-molecular-weight protein
produced by nucleated cells.






37
It is freely filtered by the glomerulus, reabsorbed, and
catabolized by the proximal tubule.
Produced at a constant rate, levels remain stable if
kidney function is normal.
Plasma concentrations appear to be unaffected by
gender, race, age, and muscle mass.
Studies have shown measurement of cystatin C to be at
least as useful as serum creatinine and creatinine
clearance in detecting early changes in kidney
function.
A rise in cystatin C is often detectible before there is a
measureable decrease in GFR or increase in creatinine.
Cystatin C can be measured by immunoassay methods.
Renal Function Tests

β2-Microglobulin




38
is a small, peptide found on the surface of most
nucleated cells
levels of β2-M remain stable in normal patients
β2-M is easily filtered by the glomerulus. About
99.9% is then reabsorbed by the proximal
tubules and catabolized.
Measurement of serum β2-M is used clinically to
assess renal tubular function in renal transplant
patients, with elevated levels indicating
organ rejection
Microalbumin




39
The term microalbuminuria describes small amounts of
albumin in urine
Urine microalbumin measurement is important in the
management of patients with diabetes mellitus, who
are at serious risk of developing nephropathy over
their lifetimes
Increased glomerular capillary permeability. This
permeability allows small (micro) amounts of albumin
to pass into the urine.
If detected in this early phase, rigid glucose control,
along with treatment to prevent hypertension, can be
instituted and progression to end-stage renal disease
(ESRD) prevented.
Case Study
Jennie had a sore throat. She did not go
to the doctor and recovered without
medication.
 However, a few weeks later Jennie was still
listless and unwell.
 She noticed that her urine was very dark
and tinged red; she was also not
producing much urine.
 Jennie’s mother took her to their primary
care physician.

40
Test
Antistreptolysin-O (ASO) titer
Plasma creatinine
Blood urea nitrogen
Plasma sodium
Creatinine clearance.
Protein in urine
Red blood cell casts
41
Result
Positive
Increased
Increased
Increased
Increased
Positive
Positive
Comment



42
As a consequence of Jennie’s streptococcal
infection, a portion of the functional units in
Jennie’s kidney lost their ability to filter waste
products from her blood.
The infection provoked an antibody response,
which resulted in the formation of antigenantibody complexes circulating in her blood, as
indicated by her high ASO titer.
The complexes caused inflammation of the renal
glomeruli, which resulted in reduction of the
filtration capability of the glomeruli and,
consequently, the reduction of the flow of waste
products from blood to urine.