1
Q
Functions of Kidney
A
- Regulation of body homeostasis
- Removal of metabolic waste products
- Removal of foreign chemicals
- Production of hormones and enzymes
2
Q
homeostasis
A
Kidneys regulate:
Water balance
Inorganic ion balance (Na⁺, K⁺, Cl⁻ etc.)
Acid–base balance
3
Q
metabolic waste products
A
Kidneys clean the blood by removing metabolic waste and excreting it in urine.
Examples of metabolic wastes:
urea
creatinine
uric acid
4
Q
- Removal of foreign chemicals
A
Kidneys eliminate substances that entered the body from outside.
Examples:
drugs (antibiotics)
food metabolites
pigments from foods (e.g., beet color in urine)
compounds causing urine odor (e.g., asparagus)
5
Q
- Production of hormones and enzymes
A
Kidneys produce or activate important regulatory molecules:
Erythropoietin (EPO)
- hormone controlling red blood cell production
Renin
- enzyme initiating the renin-angiotensin system
- regulates blood pressure and sodium balance
1,25-dihydroxyvitamin D (active vitamin D)
- produced by activation in kidney
- regulates calcium balance
6
Q
Kidney failure leads to:
A
Kidney failure leads to:
anemia (low erythropoietin)
hypocalcemia (low active vitamin D).
7
Q
What are the basic anatomical features of the kidneys?
A
Kidneys are paired organs: ~150 grams each
Behind the peritoneum on either side of the
vertebral column against the posterior abdominal
wall
Renal = pertaining to the kidneys
8
Q
Location of kidney
A
Kidneys are located:
behind the peritoneal cavity
against the posterior abdominal wall
on both sides of the vertebral column
Thus kidneys are retroperitoneal organs.
9
Q
Connection to urinary system
A
Urine flows through the following pathway:
Kidney → ureter → bladder → urethra → outside body.
Important terminology:
Renal = relating to kidneys.
10
Q
What are the major structural regions of the kidney?
A
- Renal cortex
- Renal Medulla
- renal pelvis
11
Q
renal cortex
A
outer lighter region
contains:
renal corpuscles
portions of tubules
12
Q
Renal medulla
A
inner darker region
organized into pyramids
contains:
loops of Henle
collecting ducts
13
Q
- Renal pelvis
A
central urine-collecting space
urine flows here before entering the ureter
Key exam fact:
Renal corpuscles are only found in the cortex, never in the medulla.
The cortex–medulla distinction is critical for understanding:
sodium handling
water regulation
urine concentration.
14
Q
How does blood flow through the kidney?
A
- Renal artery
- Interlobar arteries
- Arcuate arteries
- Interlobular arteries
- Afferent arterioles
- Glomerular capillaries
- Efferent arterioles
- Peritubular capillaries
- Venous system → renal vein
~20% of cardiac output goes to the kidneys.
The afferent arteriole is especially important because it supplies blood to the nephron, the kidney’s functional unit.
Venous drainage generally mirrors the arterial pattern, so separate memorization is not required.
15
Q
Nephron
A
The nephron is the functional unit of the kidney.
Each kidney contains about:
~1 million nephrons
Thus a person with two kidneys has roughly:
~2 million nephrons total.
16
Q
Each nephron has two major components
A
- Renal corpuscle
Initial filtration structure.
Components:
Glomerulus
Bowman’s capsule
- Renal tubule
Long tubular system where filtrate is modified.
Overall structure:
Renal corpuscle → tubule → collecting duct → renal pelvis.
This system performs filtration, reabsorption, and secretion, producing urine.
17
Q
What are the segments of the nephron tubule?
A
What are the segments of the nephron tubule?
After the renal corpuscle, filtrate flows through several segments.
Proximal tubule
Two parts:
Proximal convoluted tubule (PCT)
Proximal straight tubule (PST)
Often simplified as proximal tubule.
Loop of Henle
Hairpin-shaped structure.
Segments:
Descending thin limb
Ascending thin limb
Thick ascending limb (TAL)
The thick ascending limb is physiologically important.
Distal convoluted tubule (DCT)
Occurs in cortex.
Collecting duct system
Two segments:
Cortical collecting duct (CCD)
Medullary collecting duct (MCD)
Final urine enters the renal pelvis.
Important spatial rule:
Nephron begins in cortex
descends into medulla
returns to cortex
then enters collecting duct → medulla.
18
Q
What is the renal corpuscle?
A
The renal corpuscle is the initial filtration unit of the nephron.
It consists of:
Glomerulus: network of entangled capillary loops
Bowman’s capsule surrounds the glomerulus and collects filtrate.
Between them is:
Bowman’s space where filtered plasma accumulates before entering the tubule.
Terminology confusion:
Renal corpuscle = glomerulus + Bowman’s capsule
In practice many clinicians use glomerulus to refer to the whole structure.
But technically they are different
19
Q
What are podocytes and what is their role?
A
Podocytes are specialized epithelial cells forming the visceral layer of Bowman’s capsule.
Characteristics:
have foot processes
these interdigitate around capillaries
form filtration slits
Function:
Podocytes are part of the glomerular filtration barrier.
Name origin:
Podo = foot
They resemble cells with many feet surrounding capillaries.
These cells are essential for preventing protein loss in urine
20
Q
glomerulus
A
Entangled capillary loops surrounded by Bowman’s
capsule
Glomerulus filters blood to make urine.
21
Q
Glomerular capillary wall
A
22
Q
What are the three layers of the glomerular filtration barrier?
A
- Capillary endothelial cells
contain fenestrations (pores) - Glomerular basement membrane (GBM)
fine mesh barrier
blocks large proteins
- Podocyte filtration slits
formed by interdigitating foot processes.
Together these layers prevent passage of:
- blood cells
- large proteins
Thus glomerular filtrate is cell-free and protein-poor
23
Q
What is the juxtaglomerular apparatus?
A
The juxtaglomerular apparatus (JGA) is a specialized region where:
the tubule returns to the glomerulus
near the afferent arteriole
Components include specialized cells such as:
macula densa
juxtaglomerular cells
Functions:
regulate renin secretion
control blood pressure
regulate glomerular filtration
The JGA links tubular function to vascular control.
24
Q
segments of the nephron
A
25
Three processes of urine
formation
1. Glomerular filtration
2. Tubular secretion
3. Tubular reabsorption
26
Glomerular filtration
Urine formation begins with the filtration of
plasma from the glomerular capillaries into
Bowman’s space (glomerular filtration).
Glomerular filtrate (fluid in Bowman’s space) is
cell-free and except for proteins, contains all the
substances in plasma in virtually the same
concentrations as in plasma
27
Tubular secretion/reabsorption
As the glomerular filtrate passes through the
tubules, its composition is altered by movements
of substances.
Tubules --> Peritubular capillaries Reabsorption
Peritubular capillaries --> Tubules Secretion
28
What is glomerular filtrate?
Glomerular filtrate is the fluid in Bowman’s space.
Properties:
- cell-free
- almost protein-free
- contains small solutes at plasma concentration
Examples of filtered substances:
Na⁺, K⁺, Cl⁻, glucose, urea, water
Large molecules like albumin normally cannot cross the filtration barrier
29
What is the relationship between filtration, secretion, reabsorption, and excretion?
Excreted = Filtered + Secreted − Reabsorbed
Definitions:
Filtered
movement from blood → Bowman’s space
Secreted
movement from peritubular capillaries → tubule
Reabsorbed
movement from tubule → blood
Excreted
final elimination in urine.
Important distinction:
Secretion ≠ excretion
secretion = movement into tubule
excretion = final urine output
30
Example 1 — Completely excreted
Filtered + secreted.
Example:
PAH (para-aminohippurate)
Used to measure renal plasma flow
31
Example 2 — Mostly reabsorbed
Example:
sodium
water
Small portion is excreted.
32
Example 3 — Completely reabsorbed
Example:
glucose
Normally no glucose appears in urine
33
How do kidneys maintain homeostasis through urine formation?
The rate of filtration, reabsorption, or secretion is subject
to physiological control.
When the body content of a substance goes above or
below normal, homeostatic mechanisms can regulate the
substance’s bodily balance by changing these rates.
e.g. If a normal person drinks a lot of water, reabsorption
of water is decreased and excess water will be excreted in
the urine
Key principle:
If body has too much of a substance → kidneys excrete it
If body has too little → kidneys reabsorb it
34
What is filtered by glomerular
filtration?
35
Forces involved in filtration
favoring filtratuin (glomerular capillary blood pressure)
- opposing filtration (fluid pressure in Bowman's space)
- net glomerular filtration pressure = PGC - PBS - pi(GC)
36
Glomerular filtration rate
Glomerular filtration rate (GFR): the volume of fluid filtered
from the glomeruli into Bowman’s space per unit time
37
what is the glomerular filtration rate regulated by
GFR is regulated by net filtration pressure
membrane permeability
surface area available for filtration
Normal GFR (70 kg person): 180 L/day (125 ml/min)
N.B. plasma volume of this person: 3.5 L
180/3.5 = 51
Plasma is filtered 51 times a day at glomeruli!
38
filtered load
Filtered load: total amount of any freely filtered substance
Filtered load = GFR x plasma concentration of the substance
e.g.
Filtered load of glucose = 180 L/day x 1 g/L = 180 g/day
Filtered load > amount excreted in the urine: net reabsorption
Filtered load < amount excreted in the urine: net secretion
39
Reabsorption: tubular lumen to peritubular capillary
40
average values for several components that undergo filtration and reabsorption
41
Important facts about tubular
reabsorption-1
1. Filtered loads are enormous, generally greater
than the amounts of the substance in the body.
2. Reabsorption of waste products is relatively
incomplete (e.g. urea).
3. Reabsorption of most useful plasma
components (e.g. water, inorganic ions, and
organic nutrients) is relatively complete.
4. Reabsorption of some substances are not
regulated (e.g. glucose, amino acids), while
others are highly regulated (water, inorganic
ions)
42
Two mechanisms of reabsorption:
diffusion and mediated transport
Reabsorption by diffusion: often across the tight
junctions connecting the tubular epithelial cells
e.g. urea reabsorption in the proximal tubule
Urea is freely filtered at glomerulus.
-->In the proximal tubule, water reabsorption occurs.
-->Urea concentration in the tubular fluid becomes
higher.
-->Urea diffuses into the interstitial fluid and peritubular
capillaries
43
Two mechanisms of reabsorption:
diffusion and mediated transport
Reabsorption by mediated transport occurs across tubular
cells (transcellular epithelial transport).
Requires the participation of transport proteins in the
plasma membrane of tubular cells. Usually coupled to the
reabsorption of sodium.
44
Mediated Transport
45
Mechanisms of solute transport
(different way to classify)
Passive: spontaneous, down an electrochemical gradient (no energy required)
Active: against an e-c gradient (requires input of
energy)
46
Transport maximum (Tm)
When the membrane transport proteins become
saturated, the tubule can not reabsorb the substance any
more. This limit is called transport maximum (Tm)
e.g. in people with uncontrolled diabetes mellitus, the
plasma concentration of glucose can become very high
and the filtered load of glucose exceeds the capacity of
the tubules to reabsorb glucose (Tm is exceeded). As a
result, glucose appears in the urine (glucosuria
47
Tubular secretion
Tubular secretion moves substances from peritubular
capillaries into the tubular lumen (opposite of
reabsorption).
Also mediated by the two mechanisms, i.e. diffusion
and transcellular mediated transport.
Most important substances secreted by the tubules:
hydrogen ion and potassium.
Tubular secretion is usually coupled to the reabsorption
of sodium
48
Division of labor in the tubules-1
In order to excrete waste products adequately, the GFR
must be very large. Thus, the filtered volume of water
and the filtered loads of all the nonwaste plasma
solutes are also very large.
Proximal tubule: reabsorbs most of this filtered water
and solutes. It is also a major site of secretion for
various solutes, except K+.
Henle’s loop: also reabsorbs relatively large quantities
of the major ions (less water
49
Division of labor in the tubules-2
DCT/CD: volume of water and masses of solutes
reaching here are relatively small. Fine-tuning.
Determines the final amounts excreted in the urine by
adjusting the rates of reabsorption, and, in a few cases,
secretion. Most homeostatic controls are exerted here
50
Concept of clearance
Clearance: the volume of plasma from which
that substance is completely removed
(“cleared”) by the kidneys per unit time
51
Inulin clearance
Inulin (not insulin) is a polysaccharide that would be
administered intravenously. It is freely filtered at
glomerulus but is NOT reabsorbed, secreted, or
metabolized by the tubule. Thus, the clearance of inulin
(CIN) is equal to the volume of plasma originally filtered
(GFR)
CIN = GFR
(most accurate marker of GFR
52
Creatinine clearance
Creatinine is a waste product produced by
muscle.
It is filtered freely at glomerulus and is NOT
reabsorbed.
It is secreted at the tubule but the amount is
small. It is NOT metabolized by the tubule.
Thus, creatinine clearance is used as a clinical
marker for GFR
53
Creatinine clearance formula
54
example of creatinine clearance
Urine volume: 2 L per day
Urine concentration of creatinine: 9.6 mmol/L
Plasma concentration of creatinine: 0.3 mmol/L
Creatinine clearance = UcrV = 9.6 x 2 = 64 L/day
Pcr 0.3
This person has lost ~2/3 of GFR
55
Clearance vs GFR
Clearance of a substance > GFR
It is secreted at the tubule.
Clearance of a substance < GFR
It is reabsorbed at the tubule
56
Total-body balance of sodium
and water
Sodium (Na) and water are important
components of the body fluids.
Total-body balance of Na and water has to
be maintained to sustain normal blood
pressure and life
57
insensible vs sensible losses in a day water gain and loss
58
daily sodium chloride intake and loss
59
water-sodium balance
water intake = water output
sodium intake = sodium output
Depending on intake:
water output can vary from 0.4 L/day to 25 L/day;
sodium chloride output can vary from 0.05 g/day
to 25 g/day
60
Basic renal processes for sodium
and water
Both sodium and water are freely filtered but
~99% is reabsorbed (no secretion).
The majority of sodium and water reabsorption
(~2/3) occurs in the proximal tubule.
But the major hormonal control of reabsorption
occurs on the DCT and CD
61
sodium reabsorption
1) Sodium reabsorption is an active process
occurring in all tubular segments (except the
descending thin limb of Henle’s loop
62
water reabsorption
2) Water reabsorption is by diffusion and is
dependent upon sodium reabsorptio
63
active sodium reabsorption on the basolateral membrane
On the basolateral membrane:
Active Na+/K+-ATPase pumps transport sodium out of
the cells and keep the intracellular concentration of sodium
low
64
active sodium reabsorption on the apical membrane
On the apical (luminal) membrane:
Sodium moves downhill from the tubular lumen into the
tubular epithelial cells. Each tubular segment has different
mechanisms.
e.g. In the proximal tubule: Na+-H+ antiporter
(counterporter)
Na+-glucose cotransporter
In the CCD: diffusion via Na+ channel
65
Renal sodium regulation
increase of sodium intake, increase urinary sodium excretion
decrease sodium intake, urinary sodium excretion
We are in sodium balance (keeping total body sodium
constant)
66
What is sensing total body
sodium?
Sodium is the major extracellular solute, thus changes in
total body sodium result in similar changes in extracellular
fluid volume
Total body sodium is sensed as intravascular filling by
baroreceptors in the cardiovascular system
67
IMPORTANT THINGS FOR PLASMA CONCENTRATION
Plasma concentration of sodium is
NOT a marker for total body
sodium.
PNa only reflects the relative
relationship of total body Na and
water
68
Renal regulation of sodium
Sodium excreted = Sodium filtered - Sodium reabsorbed
(sodium is NOT secreted in the tubules
69
Sodium excretion could be regulated by
1. GFR (minor role)
2. Sodium reabsorption (most important
70
Renal regulation of
sodium-control by GFR
71
Renal regulation of sodium
-control by reabsorption
Key hormone: aldosterone (steroid hormone secreted by
the adrenal cortex, zona glomerulosa )
Aldosterone stimulates sodium reabsorption in the DCT
and CCD.
No aldosterone: ~2 % of filtered load is excreted
(equivalent to 35 g of sodium chloride).
High aldosterone: ~0 % of filtered load is excreted
72
Na reabsorption
73
74
Regulation of aldosterone
secretion: renin-angiotensin
system
75
Juxtaglomerular apparatus
76
Regulation of renin
secretion
by extracellular fluid volume
Aldosterone does NOT
stimulate H2O
reabsorption directly in
the CCD
important mechanisms for Na balance
77
Other factors influencing renal
sodium excretion
Atrial natriuretic peptide (ANP)
Blood pressure
78
Atrial natriuretic peptide (ANP)
Other factors influencing renal
sodium excretion
Atrial natriuretic peptide (ANP)
* ANP is a peptide hormone secreted by cells in the cardiac
atria.
* ANP acts on the tubules to inhibit sodium reabsorption
(opposite actions of aldosterone) and increases GFR.
* Increased total body sodium (thus increased extracellular
fluid/plasma volume) stimulates ANP secretion
79
Blood pressure
* Increased blood pressure increases sodium excretion (pressure
natriuresis)
80
Action of ANP
81
Osmolarity
total solute concentration of a solution; measure of water concentration in that the higher the solution osmolarity, the lower the water concentration
82
Hypoosmotic
having total solute concentration less
than that of normal extracellular fluid (300 mOsm
83
Isoosmotic
having total solute concentration equal to that of normal extracellular fluid
84
Hyperosmotic
having total solute concentration
greater than that of normal extracellular fluid
85
average daily water gain and loss in adults
86
Renal regulation of water balance
* Water is freely filtered but ~99% is reabsorbed
- balance of 1% makes up the urine
* The majority of water reabsorption (~2/3)
occurs in the proximal tubule.
* But the major hormonal control of reabsorption
occurs in the CD
87
Water reabsorption depends on Na reabsorption (proximal tubule)
MEMORIZE DIAGRAM
1. Na is reabsorbed from the tubular lumen to the
interstitial fluid across the epithelial cells.
2. The local osmolarity in the lumen decreases, while the
local osmolarity in the interstitium increases.
3. This difference in osmolarity causes net diffusion of
water from the lumen into the interstitial fluid.
via tubular cells’ plasma membranes via tight junctions
4. From the interstitium, water, sodium, and everything
else dissolved in the interstitial fluid move together by
bulk flow into peritubular capillaries
88
Maintenance of water balance
The body has to maintain water balance.
* When the water intake is small, the kidney reabsorbs
more water (e.g. urine output 0.4 L per day).
* When the water intake is large, the kidney reabsorbs less
water (e.g. urine output 25 L per day).
This dynamic regulation takes place in the medullary
collecting duct
89
Urine concentration:
countercurrent multiplier system
* The kidney has the ability to concentrate urine up to 1400
mOsm/L.
* Urinary concentration takes place as tubular fluid flows through
the medullary collecting ducts.
* Urinary concentration depends on the hyperosmolarity of the
interstitial fluid. In the presence of vasopressin, water diffuses out
of the ducts into the interstitial fluid in the medulla to be carried
away.
* How does the medullary interstitial fluid become
hyperosmotic ?
90
Urine concentration:
countercurrent multiplier system
The medullary interstitial fluid becomes hyperosmotic
through the function of Henle’s loop
91
Countercurrent multiplier system step 2
91
Countercurrent multiplier system Step 1
92
Countercurrent multiplier system (MOVE)
93
Countercurrent multiplier system (AFTER THE MOVE)
94
summary of interstitial hyperosmolarity and gradient
vascular system helps maintain
95
Vasa recta
blood vessels in the
medulla
Its hairpin-loop
structure, minimizes
excessive loss of
solute from the
interstitium
In addition to NaCl,
urea also contributes
to medullary
hyperosmolarity
- vessels make hairpin curve identical to the limb
- blood washes the solutes away
- loss is minimized due to hairpin curve
96
Water permeability of the tubules
* Water reabsorption depends on the water permeability of
the tubules.
* Permeability of the epithelium depends on the tubular
segment.
e.g. proximal tubule: high permeability to water
* Permeability largely depends on the presence of water
channels (termed aquaporins) in the plasma membrane.
* Water permeability (regulated by the amount of
aquaporins in the plasma membrane) in the CCD and
MCD is subject to physiological control and vasopressin
is the key hormone in this control
97
Hormonal
control
(vasopressin)
98
Vasopressin
Peptide hormone, also called anti-diuretic hormone (ADH)
- Produced by a group of hypothalamic neurons
- Released from the posterior lobe of the pituitary gland
- Couples to GPCR V1 (smooth muscle) and V2 (kidney)
- Vasopressin stimulates the insertion of aquaporins in the
luminal membrane of the collecting duct cells and
increases the water permeability
99
when vasopressin is present
When vasopressin is present, collecting ducts become
permeable to water ----> water reabsorption
100
when vasopressin isn't present
When vasopressin is not present, collecting ducts
become impermeable to water ----> water diuresis
101
Diabetes insipidus
Diabetes insipidus (DI) is caused by malfunction of the
vasopressin system (vasopressin does NOT work
- constant peeing
- could be caused by deficiency in vasopressin or defect
102
diagram with vasopressin
when fluid enters cortical collecting duct, the surrounding osmolarity is hypo-osmotic
- as fluid moves down medullary part, it is surrounded by increasing osmolarity
- since vasopressin is present, water is pulled from tubular lumen to the interstitial, then taken away by vasopressin to be recycled
- active water reabsorption occurs when vasopressin is there
103
diagram without vasopressin
when you don't have vasopressin, then the fluid that enters cortical collecting duct is as low as 50. altho tubule is surrounded by high osmolarity, since there is no vasopressin, water can't move back to interstitial space
- so osmolarity is low, and person will do diluted urine
104
Regulation of vasopressin
Water excretion is mainly regulated by the rate of water
reabsorption from the tubules. Vasopressin regulates this
rate. Hence, vasopressin is a major regulator of water
excretion
105
2 mechanisms to regulate vasopressin secretion
1. Osmoreceptor control (most important)
2. Baroreceptor control (less sensitive
106
Osmoreceptor
control of
vasopressin
secretion
very sensitive
107
Baroreceptor
control of
vasopressin
secretion
108
Why do we feel thirsty ?
sensed by osmoreceptors, increase of plasma osmolarity
- if plasma volume is low, then baroreceptors kick in (less sensitive than the osmoreceptors)
109
severe sweating
plasma solute concentration isn't a good marker
- high sodium concentration means that water loss is larger than sodium loss
- looking at the person at a whole means not enough sodium
- heat wave = lots of elderly people died
- many people got sick rapidly (hypernatremia)
110
Hyperkalemia
high concentration of K in the
extracellular fluid (>5 mEq/L)
cause abnormal rhythms of the heart and
abnormalities of skeletal muscle contraction
111
Potassium regulation
Potassium (K) is the most abundant intracellular ion.
98% Intracellular fluid
2% Extracellular fluid
The K concentration in the extracellular fluid is
extremely important for the function of excitable
tissues (nerve and muscle).
Reason: the resting membrane potentials of these
tissues are directly related to the relative intracellular
and extracellular K concentrations
112
Hypokalemia
low concentration of K in the
extracellular fluid (<3.5 mEq/L
Both cause abnormal rhythms of the heart and
abnormalities of skeletal muscle contraction
113
Effect of hyperkalemia on the
electrocardiogram- pre cardiac arrest
114
115
Potassium balance
maintained by kidney
of dietary intake, 90% is excreted in urine, and 10% is excreted by feces and sweat
116
Renal regulation of potassium
K is freely filtered at glomerulus.
Normally, the tubules reabsorb most of this
filtered K so that very little of the filtered K
appear in the urine.
However, unlike sodium or water, K can be
secreted at the cortical collecting ducts
117
Changes in K excretion
are due mainly to
changes in K secretion in the CCD (some in the
DCT)
118
119
120
Potassium secretion is regulated by
1. Dietary intake of potassium
2. Aldosterone
121
Regulation of K+
secretion by
dietary intake
and aldosterone
122
K+ secretion can
occur when renin-
aldosterone system
is activated by
other causes
123
Hyperaldosteronism
* The conditions in which the adrenal hormone
aldosterone is released in excess.
* The most common cause: adenoma of the
adrenal gland that produces aldosterone
autonomously.
* Increased fluid volume, hypertension,
hypokalemia. Renin is suppressed. Metabolic
alkalosis is often seen
124
Hydrogen ion regulation
Metabolic reactions are highly sensitive to the
hydrogen ion concentration of the environment.
Thus, the hydrogen ion concentration of the
extracellular fluid is tightly regulated.
pH: ~7.4 ([H+]: ~40 nmol/L)
125
Important mass reaction
When bicarbonate ion is lost from the body, it is the
same as if the body had gained a hydrogen ion.
Conversely, when the body gains a bicarbonate ion, it is
the same as if the body had lost a hydrogen iron
126
Hydrogen Gain
1. Generation of hydrogen ions from CO2
2. Production of non-volatile acids from metabolism of protein and other organic molecules
3. gain of hydrogen ions due to loss of bicarbonate in diarrhea or other nongastric GI fluids
4. Gain of hydrogen ions due to loss of bicarbonate in the urine
127
Hydrogen loss
1. utilization of hydrogen ions in the metabolism of various organic anions
2. loss of h ions in vomitus
3. loss of h ions in urine
4. hyperventilation (loss of CO2)
128
Nonvolatile acids
Phosphoric acid
Sulfuric acid
Lactic acid
Average net production: 40-80 mmol of H+ per day
129
Buffer of hydrogen ion
Any substance that can reversibly bind hydrogen ions is
called a buffer. Most hydrogen ions are buffered by
extracellular and intracellular buffers.
pH = -log [H+]
Normal ECF pH 7.4 corresponds to 40 nanomoles/L of H+.
Without buffering, hydrogen ion concentrations changes a
lot
130
Major extracellular buffer is the CO2/HCO3- system.
Major intracellular buffers are phosphates and
proteins.
Buffering does not eliminate hydrogen ions from the
body. It only keeps them “locked up
131
Ultimate balance of hydrogen ion
is controlled by
Respiratory system (by controlling CO2)
Kidneys (by controlling HCO3-)
Both systems work together to minimize the
change of hydrogen ion concentration (pH)
132
Low H+ concentration (alkalosis)
Kidneys excrete HCO3-
(high pH: alkalosis)
Respiratory alkalosis (results from altered respiration)
Metabolic alkalosis (results from other causes)
133
High H+ concentration (acidosis)
Kidneys produce new
(low pH: acidosis) HCO3- and add to the
plasma
Respiratory acidosis (results from altered respiration)
Metabolic acidosis (results from other causes
134
Renal mechanisms of hydrogen
ion control: via control of HCO3-
135
Henderson-Hasselbalch equation
136
Ka
dissociation constant for CO2/HCO3- system
0.03 is solubility of CO2 at 37OC
137
Renal handling of HCO3
HCO3- excretion =
HCO3- filtered (+ HCO3- secreted) - HCO3- reabsorbed
Normally, the kidneys
reabsorb all filtered
HCO3-.
Exception: alkalosis
Also mediated by
H+/K+-ATPase
Na+/H+ antiporter
138
139
Addition of new HCO3- to the plasma
is achieved
1. by H+ secretion and excretion on
nonbicarbonate buffers (such as phosphate).
2. by glutamine metabolism with NH4+ excretion.
Both processes could be viewed as H+ excretion by the
kidney.
The kidneys normally contribute enough new HCO3- to the
plasma to compensate for the hydrogen ions from
nonvolatile acids generated in the body (40-80 mmol/day
140
Addition of new HCO3- to the plasma-1
This happens only
after all the HCO3-
has been
reabsorbed and is
no longer
available in the
lumen
141
Addition of new HCO3- to the plasma-2
Mainly in
proximal
tubule
This process is
also called “H+
excretion bound
to NH3”
142
Renal responses to acidosis
Responses to acidosis (high H+ concentration)
1. Sufficient H+ are secreted to reabsorb all the filtered HCO3-.
2. Still more H+ are secreted and this contributes new HCO3- to
the plasma as these H+ are excreted bound to non-HCO3- buffer
such as HPO42-.
3. Tubular glutamine metabolism and ammonium excretion are
enhanced, which also contributes new HCO3- to the plasma.
143
result of Renal responses to acidosis
Net result: More new HCO3- than usual are added to the plasma,
thereby compensating for the acidosis. The urine is highly acidic
(lowest attainable pH = 4.4)
144
Responses to alkalosis (low H+ concentration)
1. Rate of H+ secretion is inadequate to reabsorb all the filtered
HCO3-, so the significant amounts of HCO3- are excreted in the urine.
2. There is little or no H+ secretion on non-HCO3- urinary buffers.
3. Tubular glutamine metabolism and ammonium excretion are
decreased, so that little or no new HCO3- is contributed to the plasma
from this source.
145
result of Responses to alkalosis
Net result: Plasma HCO3- will decrease, thereby compensating for
the alkalosis. The urine is highly alkaline (pH > 7.4
146
Classification of acidosis and
alkalosis
147
148
Respiratory acidosis
Respiratory acidosis: respiratory failure with CO2 retention
149
Respiratory alkalosis
Respiratory alkalosis: hyperventilation (e.g. high altitude)
150
Metabolic acidosis:
Metabolic acidosis: diarrhea (loss of HCO3- in diarrhea),
renal failure (accumulation of inorganic acids
151
Metabolic alkalosis
vomiting (loss of H+ in vomits),
hyperaldosteronism (increased H+ secretion in DCT and
CCD)
152
Diuretics
Drugs used clinically to increase the volume of urine
excreted are known as diuretics.
Diuretics act on the tubules to inhibit the reabsorption of
sodium, along with chloride and/or bicarbonate, resulting
in increased excretion of these ions. Water excretion
increases, too
153
Loop diuretics
* Acts on the thick ascending limb of the loop of Henle.
* Inhibits cotransport of sodium, chloride and
potassium (Na+-K+-2Cl- cotransporter).
* One of the commonly used diuretics.
* e.g. furosemide
154
Potassium-sparing diuretics
* Inhibit sodium reabsorption in the CCD, and also
inhibits potassium secretion there. Thus, unlike the other
diuretics, plasma concentration of potassium does not
decrease.
* Either block the action of aldosterone or block the
(aldosterone-regulated) epithelial sodium channel in the
CCD.
* e.g. amiloride, spironolactone
155
Clinical use of diuretics
* Renal retention of salt and water: abnormal expansion
of the extracellular fluid (edema
156
congestive heart failure
Example 1: congestive heart failure (cardiac failure
leading to lower cardiac output
157
hypertension
Example 2: hypertension. In some patients with
hypertension, renal retention of salt and water
contribute to high blood pressure
158
Common features of kidney disease/kidney failure
Proteinuria (protein in the urine)
Accumulation of waste products in the blood
(urea, creatinine, phosphate, sulfate)
High potassium concentration in the blood
Metabolic acidosis
Anemia (decreased secretion of erythropoietin)
Decreased secretion of 1,25-(OH)2vitamin D
(leading to hypocalcemia
159
Treatment of kidney (renal)
failure
When more than 90 % of nephrons stop
working, one can not sustain life. In order to
continue living, one has to have renal
replacement therapy
160
Renal replacement therapy:
1. Hemodialysis
2. Peritoneal dialysis
3. Kidney transplantation
161
Hemodialysis
162
163
Peritoneal dialysis
The lining of the patient’s own abdominal cavity
(peritoneum) is used as a dialysis membrane.
Fluid is injected into the cavity via a tube inserted
through the abdominal wall.
Solutes diffuse into the fluid from the person’s
blood.
Fluid is exchanged several time per day
164
Kidney transplantation
Either from recently deceased persons (cadaveric
transplant) or from a living related/unrelated
donor.
Anti-rejection treatments have improved
dramatically in recent years. Organ shortage is a
problem.
Donors can function quite normally with one
kidney
PHGY 210
flashcards
Decks in class (5)
# Cards
