RENAL PHYSIOL-

OGY

Dr I.G
BODY FLUID COMPARTMENT
 Total body water (40L=60%) is found being distributed inside the body in the fluid
compartments
 Fluid compartments:
 Intracellular fluid compartment (25L) =40%
 Extracellular fluid compartment (15L) =20%

 The ECF furthermore has two sub-compartments:

 Interstitial fluid compartment =15%

 Intravascular compartment (plasma) =5%

 Others....

 The proportion of fluid in each of the fluid compartments should be

maintained constant.
 The maintenance of a relatively constant volume and a stable
composition of the body fluids is essential for homeostasis.

 The relative constancy of the body fluids is remarkable be-

cause there is continuous exchange of fluid and solutes with
the external environment as well as within the different com-
partments of the body.
 For example, there is a highly variable fluid intake that must be

carefully matched by equal output from the body to prevent

body fluid volumes from increasing or decreasing.
 Daily Intake of Water
 Water is added to the body by two major sources:

 It is ingested in the form of liquids or water in the food, which

is about 2100 ml/day
 It is synthesized in the body as a result of oxidation

of carbohydrates, adding about 200 ml/day.

 This provides a total water intake of about 2300 ml/day .

Daily Loss of Body Water
 This can be via sensible means or insensible water Loss.

About 700 ml/day of water is lost through evaporation from the

respiratory and diffusion through the skin under normal condi-
tions.
 This is termed as insensible water loss because we are not

consciously aware of it, even though it occurs continually in all

living humans.
Water is also lost via sensible route i.e., in the form of urine and
sweat.
The relative amounts of ECF distributed between
the plasma and interstitial spaces are mainly controlled by two
forces:
 Hydrostatic pressure: it is the force exerted by a fluid against

the surface of the compartment containing fluid.

 Osmotic pressure: Is the pressure that must be applied to a so-

lution on one side of a selectively permeable membrane to pre-

vent the Osmotic flow of water across the membrane from a
compartment of pure water.
 The distribution of fluid between ECF and ICF compartments,
in contrast, is determined mainly by the osmotic effect of the
smaller solutes— especially sodium, chloride, and other elec-
trolytes— acting across the cell membrane.
 The reason for this is that the cell membranes are highly per-

meable to water but relatively impermeable to even small ions

such as sodium and chloride.

 Therefore, water moves across the cell membrane rapidly, so

that the ICF remains isotonic with the ECF; 280 to
DISTURBANCE IN BODY FLUIDS
 This can be
 Fluid excess (hypervolemia) or
 Fluid deficit (hypovolemia) also called dehydration
 Hypervolemia may be caused as a result of:
 Heart disease
 Renal disease
 Liver disease
 Protein malnutrition
 Mismanagement of intravenous fluid
 Hypovolemia may be caused due to
 Hemorrhage
 Excessive diarrhea
 Excessive vomiting
 Excessive sweating .....
ELECTROLYTES
 Electrolytes are compounds that dissociate in to ions when in
solutions.
 Acids, bases & salts are electrolytes.

 Most electrolytes are dissolved in the body fluids.

 However, some are found attached to proteins and other places.

 The most physiologically important electrolytes are the cations

(Na+, k+, ca2+ mg2+ and H+) and anions bicarbonates

(HCO3-), chloride (cl-) phosphate (HP04 2) & sulfate (SO42-)
FUNCTIONS.
 Necessary for cell metabolism & contribute to body struc-
ture.
 Facilitate movement of water between the body compartments

 Together with the soluble proteins, they maintain the hydrogen

ion Concentration (acid-base balance)

 Sodium, potassium, chlorides and magnesium are crucial to

the production and maintenance of membrane potentials (n-

erve & muscle potentials)
 Na, K and Cl ions present in the highest concentration in the

body.
 Major Functions of the Kidneys
14

 1. Regulation of:
 Body fluid osmolarity and volume
 Electrolyte balance
 Acid-base balance
 Blood pressure
 2. Excretion of
 Metabolic products
 Foreign substances (drugs and other chemicals etc.)
 Excess substances (water, etc)
15

3. Secretion of
Erythropoeitin


1,25-dihydroxy vitamin


D3 (vitamin D activation)


Renin


Prostaglandin


4. Involved in gluconeogenesis

 Gross Anatomy of the Kidney
16

• Kidneys are paired brownish structures

• Are bean-shaped
• are located retroperitoneally in the ab-
dominal cavity
• Vertically extend from T12-L3
• Positionally, the right kidney is slightly
lower than the left because of mass of
liver pushing it down
 Microanatomy of the Kidneys
17
 The Nephron
Nephrons are functional and structural
units of the kidney i.e. individually
and collectively they perform the
functions of the kidneys. Glomerulus
Each kidney is made up of about 1 mil-
lion nephrons

Each nephron has two major compo-

nents:
 A glomerulus
 A long tube (Renal tubules)

Dr Gemechu. T 08/17/202218
19

 Glomerulus → Proximal tubule (cortex) →loop of Henle (medulla)

→distal tubule (cortex) → cortical collecting tubule → medullary col-
lecting tubule → collecting duct.
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 Blood Supply to the Kidney
21
22

T
 The Juxtaglomerular Apparatus
23

 The juxtaglomerular apparatus is a place where the distal con-

voluted tubule lies close to the glomerulus as well as the affer-
ent and efferent arterioles.
 Within the JGA is a group of cells lining the distal tubule called
the macula densa (chemoreceptors)
 Macula densa cells sense the glomerular filtration rate via the salt
(Na+) concentration in the distal tubule.
 Juxtaglomerular cells secrete renin into the blood of the arterioles.
24

Dr Gemechu. T 08/17/2022
 Response to ↓GFR and ↓glomerular pressure
25

 macula densa causes the juxtaglomerular cells lining to secrete

renin.
 Renin acts as an enzyme to cause a substance already in

the blood, angiotensinogen, to undergo change to

become angiotensin I, which is then converted to angiotensin II
by angiotensin converting enzyme.

Dr Gemechu. T 08/17/2022
26

 Angiotensin II acts as a vasoconstrictor, first causing vasoconstric-

tion in the efferent arteriole. Since the efferent arteriole is the out -
flow from the glomerulus, constricting it rapidly raises glomerular
pressure.
 Angiotensin II also causes the adrenal cortex to release aldos-
terone.
 Aldosterone acts on the distal convoluted tubule to increase Na+
reabsorption. More sodium reabsorption means more water reab-
sorption, and more water reabsorption means and increase in blood
pressure.
27

 The macula densa also acts directly on the afferent arteriole and
cause it to vasodilate. So at the same time the efferent arteriole is
constricting, the afferent arteriole is dilating bringing in more blood
and the combination dramatically raises glomerular pressure and
GFR.
 Response to ↑ Glomerular Pressure
28

 Myogenic response: ↑ glomerular pressure in the AA causes the

JGCs which are modified smooth muscle cells, to constrict, reducing
BF into the glomerulus.
 The only mechanism responsive to ↑ BP is the direct myogenic au-
toregulation of the AA.
 Mechanisms of Urine Formation
29

Urine formation and adjustment

of blood composition involves
three major processes
Glomerular filtration

Tubular reabsorption

Tubular Secretion
 Glomerular Filtration
30

 Fluid pressure forces water and dissolved substances out of the

blood into Bowman's capsule.
 Occurs as fluids move across the glomerular capillary in response to
glomerular hydrostatic pressure blood enters glomerular capillary.
 GFR averages 125 ml/min for your two kidneys.
 This amounts to about 180 L per day. GFR = Kf x Net Filtration Pres-
sure
 Determinants of GFR are:
31

 Glomerular hydrostatic pres-

sure
 Glomerular colloid oncotic
pressure
 BMC hydrostatic pressure
32

 Changes in GCHP are the primary

means by which GFR is altered
under physiological conditions
Determined by
 Arterial pressure
 Afferent arteriolar resistance
 Efferent arteriolar resistance
33

 Filtration involves the small molecules:

Water,Electrolytes ,Urea,Glucose & Amino acids.
 It does not involve the blood proteins and blood cells.
 The large amount of filtration is the result of the porous glomerular
membrane and filtration slits in the visceral layer of Bowman's cap-
sule.
34

Factors determining the glomerular filterability:

 Molecular weight
 Substances with small molecular weight will be filtered

 Charges of the molecule

 Negatively charged substances are repelled
 Use of Clearance Methods to Quantify KidneyFunction
35
 By definition, the renal clearance of a substance is the volume of
plasma that is completely cleared of the substance by the kid-
neys per unit time.
 Cs = Us x V units = ml/min
Ps
 Where: Cs = The clearance rate of the substance
 Us = Urine concentration of the substance
 V = Urine flow rate
 Ps = Plasma concentration of the substance

 e.g. of substances used for this purpose include: insulin, creati-

nine.These substances are neither reabsorbed nor secreted
 Concept of reaborption
36

Reabsorbtion: 2nd Step in urine forma-

tion
•Process of returning filtered materi-
als to the blood stream
•99% of what is filtered
•May involve transport proteins)
•Normally amino acids and
glucose is totally reabsorbed

Dr Gemechu. T 08/17/2022
37

 Most reabsorption occurs in Proximal convoluted tubules

 Reabsorption of water also occurs from the descending limb of the
Loop of Henle,
 Reabsorption of salt from the ascending limb and the DCT
 more water from the Collecting Duct.
38

 Proximal Tubules (PT) Have a High Capacity for Active and Passive
Reabsorption.
 H20 is pulled by osmosis into hypertonic blood. 65% occurs in PCT
 NaCl – active transport of either Na+ or Cl-, pulls water along.
 65% of NaCl reabsorption occurs in PCT
 100% of glucose and amino acid transported occurs in PCT by active
co-transport.
39

 Glucose has a treshold for its

reabsorption (i.e., 200mg%).
When BGL exceeds this value,
it starts appearing in the urine.

Dr Gemechu. T 08/17/2022
 Reabsorption from the Loop of Henle
40

 Active reabsorption of NaCl from the ascending limb →osmosis of

H2O from the descending limb by making the medulla hypertonic.
 As the filtrate enters the descending limb of the loop of Henle, it is
exposed to increasingly hypertonic medulla→pulls at least another
20% of absorbable water out of the filtrate.
 Reabsorption here is termed obligatory because it must occur due to
the ↑osmolarity of the surrounding interstitial fluid.
41
 The countercurrent exchange of salt in the vasa recta
42
43

 NaCl is picked up by the descending limb of the vasa recta.

 NaCl is released into the medulla by the ascending limb of the vasa
recta.
 This mechanism recycles the salt and keeps the deep medulla hy-
pertonic.
 From the ascending limb of Henle’s loop through the distal convo-
luted tubule the nephron is impermeable to water.
 This prevents the reabsorbed water from being lost to the urine.
 Reabsorption of NaCl from DCT
44

 Reabsorption of salt continues

into the DCT under the control
of the hormone called aldos-
terone. Aldosterone is one of
the group of hormones from
the adrenal cortex called min-
eralcorticoids which regulate
salt levels in the body.
45

Dr Gemechu. T 08/17/2022
 Reabsorption of water from the CD
46

 When the filtrate, now nearly urine,

passes through the medulla again in
the collecting tubule it is once again
exposed to the hypertonicity of the
deep medulla.
 This has the potential to pull more
water out by osmosis.
 But reabsorption of water from the
collecting tubule is facultative be-
cause it is under control of the
hormone ADH.
 K+ regulation
47
 K+ is reabsorbed in the PCT & ALH
only about 8 % of the filtered load
is delivered to DCT
 Secretion of potassium late distal
tubules CD daily excretion is about
12% of the K filtered at the
glomerularcapillaries. K+ secretion
is influenced by aldosterone
 Control of Renal Ca2 Concentration
48

 ECF Ca2 concentration normally remains tightly controlled within a

few percentage points of its normal level, 2.4 mEq/L.
 Almost all the Ca2 in the body (99 %) is stored in the bone
 only about 1 percent in the ECF
 0.1 percent in the ICF
 One of the most important regulators of bone uptake and release of
calcium is Parathyroid hormone (PTH).
49
Dr Gemechu. T 08/17/202250
 Secretion
51

 Secretion is the 3rd process in urine formation (transport of sub-

stances from the tissue to the renal tubules)
 Occurs as an active transport by the cells of the nephron tubule in
which they transport substances obtained from the peritubular
blood or interstitial fluid into the nephron tubule.
a. It occurs in the proximal convoluted tubule, distal convoluted
tubule, and collecting tubule.
52

 Secretion is done for three

purposes:
1. To release any residues from
toxins and drugs which
haven't been filtered
2. To establish electrolyte bal-
ance
3. To maintain ABB
 Mechanism of formation of concentrated urine
53 When there is a shortage of H2O in the body
↓
↓ECF volume, ↑Osmolality
Stimulates osmoreceptors in the HT
↓
↑ADH secretion
↓
↑ H2O reabsorption in the DT and CD
↓
↑Excretion of solutes
↓
Concentrated (1200 mosm/l), in
small volume of urine is produced
 Mechanism of formation of diluted urine
54 When there is excess H2O in the body
↓
↑ECF vlume, ↓Osmolality
↓
Aldosterone secretion
↓ADH secretion
↓
NaCl reabsorption in the DCT & CD
↓
↑H2O excretion
Diluted urine (50-100 mosm/l)
55