Transcript Keto acid + Amino acid

Renal System Physiology and Fluid,
Electrolyte, and Acid-Base Balance
Human
Anatomy and
Physiology II
Proteinuria
 Ellen, a 47 year old woman who has suffered from
kidney disease for several years has been diagnosed
with proteinuria. Her legs and feet are so swollen that
she has difficulty walking. Her hands and her left arm
are also swollen. What is proteinuria, and could this
condition play a role in her swollen limbs?
 Proteinuria: abnormal urine constituents of protein.
Nonpathological proteinuria: excessive physical
exertion, pregnancy
 Pathological (over 150 mg/day): heart failure, severe
hypertension, glomerulonephritis (often initial sign of
asymptomatic renal disease)
Chemical Composition of Urine
 95% water and 5% solutes
 Nitrogenous wastes: urea, uric acid, and creatinine
 Other normal solutes
 Na+, K+, PO43–, and SO42–,
 Ca2+, Mg2+ and HCO3–
 Abnormally high concentrations of any constituent
may indicate pathology
Nitrogenous Wastes
 Harmful to body/ primary component of urine
 Before amino acids can be oxidized for energy, they
must be deaminated (removal of NH2 (amine group) )
 Transamination: transfer of amine group to another acid,
thereby forming a new keto acid
 Oxidative deamination: liver removes amine group as ammonia
(NH3) which then combine with CO2 to become urea
 Keto acid modification: making keto acids to go into Krebs cycle
 Creatinine: from breakdown of creatine P
 Uric acid: end product of nucleic acid metabolism
Transamination
Amino acid + Keto acid
(a-ketoglutaric acid)
Liver
3 During keto
acid modification
the keto acids
formed during
transamination are
altered so they can
easily enter the
Krebs cycle
pathways.
1 During
transamination
an amine group
is switched from
an amino acid to
a keto acid.
2 In oxidative
deamination, the
amine group of
glutamic acid is
removed as
ammonia and
combined with CO2
to form urea.
Keto acid + Amino acid
(glutamic acid)
Oxidative
deamination
NH3 (ammonia)
Keto acid
modification
Urea
CO2
Modified
keto acid
Blood
Enter Krebs
cycle in body cells
Krebs
cycle
Urea
Kidney
Excreted in urine
Figure 23.16
Keto acids ≠ Ketones
Keto-acids
 Associated with protein
metabolism
 Proteins are metabolized into
amino acids usually for other
proteins
 Some amino acids are glucogenic
and can be used for
gluconeogenesis
 Some are ketogenic and can be
modified to produce acetyl-CoA
and enter Krebs cycle
Ketones
 Associated with lipid metabolism
 Usually for gluconeogenesis
 Liver metabolizes fatty acids and
produces ketones which it releases
into blood
 Ketones can then be used to make
acetyl-CoA and put into Krebs
cycle
 Both ketones and keto-acids can
ultimately cause ketoacidosis, but
usually from ketones and lack of
insulin
ID the ketogenic vs glucogenic amino acids
Glycolysis
Glucose
Stored fats
in adipose
tissue
Dietary fats
Glycerol
Triglycerides
(neutral fats)
Lipogenesis
Fatty acids
Ketone
bodies
Ketogenesis (in liver)
Glyceraldehyde
phosphate
Pyruvic acid
Certain
amino
acids
Acetyl CoA
CO2 + H2O
+
Steroids
Bile salts
Catabolic reactions
Cholesterol
Krebs
cycle
Electron
transport
Anabolic reactions
Figure 23.15
Creatine Phosphate
Renal Homeostatic Imbalances
 Rachael has been complaining of frequent and
burning urination, fever, chills and back pain. She
also reported seeing some blood in her urine. Her
physician suspects cystitis. What is cystitis and how
can it cause these symptoms? How is cystitis related
to urinary tract infections? Name two preventive
behaviors for UTI.
 Cystitis: Inflammation of the urinary bladder. Most
often caused by bacterial infection and called UTI.
 UTI: technically an infection (bacterial) of any part of
urinary system, most often urethra and bladder
Peritoneum
Ureter
Rugae
Detrusor
muscle
Ureteric orifices
Bladder neck
Internal urethral
sphincter
External urethral
sphincter
Urogenital diaphragm
(b) Female.
Trigone
Urethra
External urethral
orifice
Figure 25.21b
Hematuria
 Urinary Tract Infections




(includes persistent urge to
urinate, pain and burning with
urination, strong smelling
urine)
Kidney infections
(pyelonephritis)…more likely to
include fever and back pain)
Bladder or kidney stone:
excruciating pain when
blockage and must pass
Medications such as aspirin,
penicillin, heparin.
Kidney injury
 Enlarged prostate compressing
urethra, includes difficulty
urinating, persistent need to
urinate
 Kidney disease
(glomerulonephritis), can be
result of systemic disease like
diabetes or triggered by viral or
strep infections
 Cancer
 Strenuous exercise, maybe due
to trauma to bladder,
dehydration, break down of
RBCs,…runners most affected
Prevention of UTI/ cystitis
 Drink plenty of water
 Drink cranberry juice



Acidity
Antioxidants
Slippery coating?
 Avoid coffee and other
stimulants, alcohol and
tobacco
 Honeymoon
cystitis…urinate before
and after
Edema
 A pregnant woman complains to her doctor that her
ankles and feet stay swollen all of the time. She is
very worried about this. As her doctor, what would
you tell her?
Fluid Compartments
 Total body water = 40 L
1.
Intracellular fluid (ICF) compartment: 2/3 or 25 L in
cells
1.
2.
In cells
Extracellular fluid (ECF) compartment: 1/3 or 15 L
 Plasma: 3 L
 Interstitial fluid (IF): 12 L in spaces between cells
 Other ECF: lymph, CSF, humors of the eye, synovial
fluid, serous fluid, and gastrointestinal secretions
Total body water
Volume = 40 L
60% body weight
Extracellular fluid (ECF)
Volume = 15 L
20% body weight
Intracellular fluid (ICF)
Volume = 25 L
40% body weight
Interstitial fluid (IF)
Volume = 12 L
80% of ECF
Figure 25.1
Fluid Movement Among Compartments
 Regulated by osmotic and hydrostatic pressures
 Water moves freely by osmosis; osmolalities of all




body fluids are almost always equal
Two-way osmotic flow is substantial
Ion fluxes require active transport or channels
Change in solute concentration of any compartment
leads to net water flow
Obviously changes in blood volume (as in pregnancy)
will change hydrostatic pressure gradients
Disorders of Water Balance: Edema
 Atypical accumulation of IF (interstitial fluid) 
tissue swelling
 Due to anything that increases flow of fluid out of
the blood or hinders its return

 Blood pressure

Capillary permeability (usually due to
inflammatory chemicals)
 Incompetent venous valves, localized blood vessel
blockage
 Congestive heart failure, hypertension,  blood
volume
Possible Causes of Edema
 Hindered fluid return occurs with an imbalance in
colloid osmotic pressures, e.g., hypoproteinemia (
plasma proteins)


Fluids fail to return at the venous ends of capillary beds
Results from protein malnutrition, liver disease, or
glomerulonephritis
 Blocked (or surgically removed) lymph vessels
 Cause leaked proteins to accumulate in IF
  Colloid osmotic pressure of IF draws fluid from the blood
 Results in low blood pressure and severely impaired
circulation
Dehydration
Body Water Content
 Infants: 73% or more water (low body fat, low bone
mass)
 Adult males: ~60% water
 Adult females: ~50% water (higher fat content, less
skeletal muscle mass)
 Water content declines to ~45% in old age
100 ml
Metabolism 10%
Foods 30%
250 ml
200 ml
750 ml
Feces 4%
Sweat 8%
700 ml
Insensible losses
via skin and
lungs 28%
1500 ml
Urine 60%
2500 ml
Beverages 60%
1500 ml
Average intake
per day
Average output
per day
Figure 25.4
Water Balance and ECF Osmolality
 Water intake = water output = 2500 ml/day
 Water intake: beverages, food, and metabolic water
 Water output: urine, insensible water loss (skin and
lungs), perspiration, and feces
Lungs
Gastrointestinal
tract
Kidneys
Blood
plasma
O2
CO2
Nutrients H2O,
Ions
H2O, Nitrogenous
Ions
wastes
Interstitial
fluid
O2
CO2
Nutrients H2O
Ions Nitrogenous
wastes
Intracellular
fluid in tissue cells
Figure 25.3
Regulation of Water Intake
 Thirst mechanism is the driving force for water intake
 The hypothalamic thirst center osmoreceptors are
stimulated by
 Plasma osmolality of 2–3%
 Angiotensin II or baroreceptor input
 Dry mouth
 Substantial decrease in blood volume or pressure
 Drinking water creates inhibition of the thirst center
 Inhibitory feedback signals include



Relief of dry mouth
Activation of stomach and intestinal stretch receptors
Plasma osmolality
Plasma volume*
Blood pressure
Saliva
Osmoreceptors
in hypothalamus
Dry mouth
Granular cells
in kidney
Renin-angiotensin
mechanism
Angiotensin II
Hypothalamic
thirst center
Sensation of thirst;
person takes a
drink
Water moistens
mouth, throat;
stretches stomach,
intestine
Initial stimulus
Physiological response
Result
Water absorbed
from GI tract
Plasma
osmolality
Increases, stimulates
Reduces, inhibits
(*Minor stimulus)
Figure 25.5
Regulation of Water Output
 Obligatory water losses
 Insensible water loss: from lungs and skin
 Feces
 Minimum daily sensible water loss of 500 ml in urine to
excrete wastes
 Body water and Na+ content are regulated in tandem
by mechanisms that maintain cardiovascular
function and blood pressure
Regulation of Water Output: Influence of ADH
 Water reabsorption in collecting ducts is
proportional to ADH release
  ADH  dilute urine and  volume of body fluids
  ADH  concentrated urine
 ADH controls the presence of aquaporins in the
collecting ducts.

Aquaporins are “water channels”
 Diabetes insipidus
 Result of inadequate ADH and excessive water lost through
urine
 Monitoring water intake will reduce effects
Regulation of Water Output: Influence of ADH
 Hypothalamic osmoreceptors trigger or inhibit ADH
release
 Other factors may trigger ADH release via large
changes in blood volume or pressure, e.g., fever,
sweating, vomiting, or diarrhea; blood loss; and
traumatic burns
Osmolality
Na+ concentration
in plasma
Plasma volume
BP (10–15%)
Stimulates
Osmoreceptors
in hypothalamus
Negative
feedback
inhibits
Stimulates
Inhibits
Baroreceptors
in atrium and
large vessels
Stimulates
Posterior pituitary
Releases
ADH
Antidiuretic
hormone (ADH)
Targets
Collecting ducts
of kidneys
Effects
Water reabsorption
Results in
Osmolality
Plasma volume
Scant urine
Figure 25.6
Disorders of Water Balance: Dehydration
 Negative fluid balance
 ECF water loss due to: hemorrhage, severe burns, prolonged
vomiting or diarrhea, profuse sweating, water deprivation,
diuretic abuse
 Signs and symptoms: thirst, dry flushed skin, oliguria
 May lead to weight loss, fever, mental confusion, hypovolemic
shock, and loss of electrolytes
Total body water
Volume = 40 L
60% body weight
Extracellular fluid (ECF)
Volume = 15 L
20% body weight
Intracellular fluid (ICF)
Volume = 25 L
40% body weight
Interstitial fluid (IF)
Volume = 12 L
80% of ECF
Figure 25.1
1 Excessive
loss of H2O
from ECF
2 ECF osmotic
pressure rises
3 Cells lose
H2O to ECF
by osmosis;
cells shrink
(a) Mechanism of dehydration
Figure 25.7a
Disorders of Water Balance: Hypotonic Hydration
 Cellular overhydration, or water intoxication
 Occurs with renal insufficiency or rapid excess water
ingestion
 ECF is diluted  hyponatremia (reduced
concentration of sodium ions)  net osmosis into
tissue cells  swelling of cells  severe metabolic
disturbances (nausea, vomiting, muscular cramping,
cerebral edema)  possible death
1 Excessive
H2O enters
the ECF
2 ECF osmotic
pressure falls
3 H2O moves
into cells by
osmosis; cells swell
(b) Mechanism of hypotonic hydration
Figure 25.7b
Acid-Base Balance
 pH affects all functional proteins and biochemical
reactions
 Normal pH of body fluids



Arterial blood: pH 7.4
Venous blood and IF fluid: pH 7.35
ICF: pH 7.0
 Alkalosis or alkalemia: arterial blood pH >7.45
 Acidosis or acidemia: arterial pH < 7.35
 Arterial pH between 7.35 and 7.0 is considered physiological
acidosis because it technically (chemically) is not acidic at this
pH
Alkalosis vs Acidosis/ Metabolic vs. Respiratory
 After travelling from Los Angeles to Denver, and
then enjoying some hiking, Claire finds she is not
feeling well and checks into a clinic for help. The
clinic’s diagnosis is respiratory alkalosis. What has
caused this problem?
 What do we know from this question?
 Claire went from sea level to high altitude, so
atmosphere has less oxygen than she is used to
 Claire went hiking right away, so she probably
exerted herself and was breathing rather
heavy…even hyperventilating trying to catch her
breath at those beautiful mountain peaks.
How do we get acidosis?
 Most H+ is produced by metabolism
 Phosphoric acid from breakdown of phosphorus-containing
proteins in ECF
 Lactic acid from anaerobic respiration of glucose
 Fatty acids and ketone bodies from fat metabolism
 H+ liberated when CO2 is converted to HCO3– in blood
Regulating Acid-Base Balance
 Concentration of hydrogen ions is regulated
sequentially by



Chemical buffer systems: rapid; first line of defense
Brain stem respiratory centers: act within 1–3 min
Renal mechanisms: most potent, but require hours to days to
effect pH changes
Physiological Buffer Systems
 Respiratory and renal systems
 Act more slowly than chemical buffer systems
 Have more capacity than chemical buffer systems
 Chemical buffers cannot eliminate excess acids or
bases from the body


Lungs eliminate volatile carbonic acid by eliminating CO2
Kidneys eliminate other fixed metabolic acids (phosphoric,
uric, and lactic acids and ketones) and prevent metabolic
acidosis
Respiratory Regulation of H+
 Respiratory system eliminates CO2
 A reversible equilibrium exists in the blood:
 CO2 + H2O  H2CO3  H+ + HCO3–
 During CO2 unloading the reaction shifts to the left
(and H+ is incorporated into H2O)

Resulting in respiratory alkalosis
 During CO2 loading the reaction shifts to the right
(and H+ is buffered by proteins)

Resulting in respiratory acidosis
Renal Mechanisms of Acid-Base Balance
 Most important renal mechanisms
Conserving (reabsorbing) or generating new HCO3–
 Excreting HCO3–
Slow process, takes day or more to readjust pH
Generating or reabsorbing one HCO3– is the same as losing one
H+
Excreting one HCO3– is the same as gaining one H+
Renal regulation of acid-base balance depends on H+secretion
H+ secretion occurs in the PCT and in collecting duct type A
intercalated cells:
 The H+ comes from H2CO3 produced in reactions catalyzed
by carbonic anhydrase inside the cells






FYI and review (the rest of powerpoint)
 Interesting information on
 Solutes
 Electrolytes
 Sodium control (remember aldosterone in water control)
 Three types of chemical buffers
(remember you need to know bicarbonate buffer system)
 Review for final exam
 Oxidation-redox reactions
 Digestive functions and where occur
 Messentery
 Epithelial change through digestion and urinary systems
 HDL, LDL, saturated and unsaturated fats
 Importance of CO2 in control of respiration, acidosis
Electrolyte Concentration
 Expressed in milliequivalents per liter (mEq/L), a
measure of the number of electrical charges per liter
of solution
 You do not need to know the formula, but just know
this is the unit by which electrolyte balance is
assessed.
mEq/L = ion concentration (mg/L)
 # of electrical
charges
atomic weight of ion (mg/mmol)
on one ion
Extracellular and Intracellular Fluids
 Each fluid compartment has a distinctive pattern of
electrolytes
 ECF

All similar, except higher protein content of plasma
Major cation: Na+
 Major anion: Cl–

 ICF:
 Low Na+ and Cl–
 Major cation: K+
 Major anion HPO42–
Proteins, phospholipids,
cholesterol, and neutral fats make
up the bulk of dissolved solutes
90% in plasma
60% in IF
97% in ICF
Composition of Body Fluids
 Water: the universal solvent
 Solutes: nonelectrolytes and electrolytes
 Nonelectrolytes: most are organic
Do not dissociate in water: e.g., glucose, lipids, creatinine, and
urea
 Have covalent bonds

 Electrolytes
 Dissociate into ions in water; e.g., inorganic salts, all acids and
bases, and some proteins
 The most abundant (most numerous) solutes
 Have greater osmotic power than nonelectrolytes, so may
contribute to fluid shifts
 Determine the chemical and physical reactions of fluids
 Usually move through active transport or channel proteins
Blood plasma
Interstitial fluid
Intracellular fluid
Na+
Sodium
K+
Potassium
Ca2+
Calcium
Mg2+
Magnesium
HCO3– Bicarbonate
Cl–
Chloride
HPO42– Hydrogen
phosphate
SO42–
Sulfate
Figure 25.2
Electrolyte Balance
 Electrolytes are salts, acids, and bases
 Electrolyte balance usually refers only to salt balance
 Salts enter the body by ingestion and are lost via
perspiration, feces, and urine
 Importance of salts




Controlling fluid movements
Excitability
Secretory activity
Membrane permeability
Central Role of Sodium
 Most abundant cation in the ECF
 Sodium salts in the ECF contribute 280 mOsm of the
total 300 mOsm ECF solute concentration
 Na+ leaks into cells and is pumped out against its
electrochemical gradient
 Na+ content may change but ECF Na+ concentration
remains stable due to osmosis
Central Role of Sodium
 Changes in plasma sodium levels affect
 Plasma volume, blood pressure
 ICF (intracellular fluid) and IF (interstitial fluid)volumes
 Renal acid-base control mechanisms are coupled to
sodium ion transport
Regulation of Sodium Balance
 No receptors are known that monitor Na+ levels in
body fluids
 Na+-water balance is linked to blood pressure and
blood volume control mechanisms
Regulation of Sodium Balance: Aldosterone
 Renin-angiotensin mechanism is the main trigger for
aldosterone release

Granular cells of JGA secrete renin in response to
Sympathetic nervous system stimulation
  Filtrate osmolality
  Stretch (due to  blood pressure)

Regulation of Sodium Balance: Aldosterone
 Na+ reabsorption
 65% is reabsorbed in the proximal tubules
 25% is reclaimed in the loops of Henle
 Aldosterone  active reabsorption of remaining Na+
 Water follows Na+ if ADH is present
Regulation of Sodium Balance: Aldosterone
 Renin catalyzes the production of angiotensin II,
which prompts aldosterone release from the adrenal
cortex
 Aldosterone release is also triggered by elevated K+
levels in the ECF
 Aldosterone brings about its effects slowly (hours to
days)
K+ (or Na+) concentration
in blood plasma*
Renin-angiotensin
mechanism
Stimulates
Adrenal cortex
Negative
feedback
inhibits
Releases
Aldosterone
Targets
Kidney tubules
Effects
Na+ reabsorption
K+ secretion
Restores
Homeostatic plasma
levels of Na+ and K+
Figure 25.8
Regulation of Sodium Balance: ANP
 Released by atrial cells in response to stretch (
blood pressure)
 Diuretic and Natriuretic Effects
 Decreases blood pressure and blood volume:



 ADH, renin and aldosterone production
 Excretion of Na+ and water
Promotes vasodilation directly and also by decreasing
production of angiotensin II
Stretch of atria
of heart due to BP
Releases
Negative
feedback
Atrial natriuretic peptide (ANP)
Targets
Hypothalamus
and posterior
pituitary
JG apparatus
of the kidney
Effects
Adrenal cortex
Effects
Renin release*
ADH release
Angiotensin II
Aldosterone release
Inhibits
Inhibits
Collecting ducts
of kidneys
Vasodilation
Effects
Na+ and H2O reabsorption
Results in
Blood volume
Results in
Blood pressure
Figure 25.9
Influence of Other Hormones
 Estrogens:  NaCl reabsorption (like aldosterone)
  H2O retention during menstrual cycles and pregnancy
 Progesterone:  Na+ reabsorption (blocks
aldosterone)

Promotes Na+ and H2O loss
 Glucocorticoids:  Na+ reabsorption and promote
edema
Bicarbonate Buffer System
 Mixture of H2CO3 (weak acid) and salts of HCO3–
(e.g., NaHCO3, a weak base)
 Buffers ICF and ECF
 The only important ECF buffer
Phosphate Buffer System
 Action is nearly identical to the bicarbonate buffer
 Components are sodium salts of:
 Dihydrogen phosphate (H2PO4–), a weak acid
 Monohydrogen phosphate (HPO42–), a weak base
 Effective buffer in urine and ICF, where phosphate
concentrations are high
Protein Buffer System
 Intracellular proteins are the most plentiful and
powerful buffers; plasma proteins are also important
 Protein molecules are amphoteric (can function as
both a weak acid and a weak base)


When pH rises, organic acid or carboxyl (COOH) groups
release H+
When pH falls, NH2 groups bind H+
Oxidation Reduction Reaction (Redox)
Oxidized Substance
Reduced Substance
 Loses energy (in form
 Gains energy (in form
of electron)
 Examples in cellular
respiration:
of electron, which is
negative charged)
 Examples:


FAD
NAD+
LEO goes GER


FADH2
NADH
Note: H is often coupled
with electron
Six Essential Activities of Digestive System
Add valves
or
sphincters:
Pyloric
Ileocecal
Ingestion
Mechanical
digestion
• Chewing (mouth)
• Churning (stomach)
• Segmentation
(small intestine)
Chemical
digestion
Cardioesophageal
Hepatopancreatic
Internal /
external
anal
Food
Pharynx
Esophagus
Propulsion
• Swallowing
(oropharynx)
• Peristalsis
Stomach (esophagus,
stomach,
small intestine,
large intestine)
Absorption
Lymph
vessel
Small
intestine
Large
intestine
Defecation
ID three
sections of
small
intestine
ID sections
of large
intestine
Blood
vessel
Mainly H2O
Feces
Anus
Figure 22.2
Liver
Lesser omentum
Pancreas
Stomach
Transverse
mesocolon
Duodenum
Transverse colon
Mesentery
Greater omentum
Jejunum
Ileum
Visceral peritoneum
Parietal peritoneum
(d)
Urinary bladder
Rectum
Figure 22.30d
Epithelial changes
Digestive Tract
Urinary Tract
 Stratified Squamous
 Transitional epithelium
 Simple Columnar Cells
 Psuedostratified
 Stratified Squamous
columnar
 Stratified squamous
Cholesterol: structural basis of bile salts,
steroids, vitamin D and membrane component
High Density Lipoproteins
Low Density Lipoproteins
 Higher protein lipoproteins,
 Higher fat lipoproteins
rich in phospholipids and
cholesterol
 Carry cholesterol from
peripheral tissues to liver,
where it is broken down to
produce bile
 Blood levels avg: 40-50
mg/dl males & 50-60 mg/dl
females
 VLDLs transport
triglycerides from liver to
peripheral tissues
 Once unloaded, VLDLs
become LDLs
 LDLs transport cholesterol
to peripheral tissues
 Blood levels ‹ 70-100 mg/dl
Relative amounts of fatty acids
affect blood
cholesterol
Unsaturated Fats
 Enhance excretion of
cholesterol and its
catabolism to bile salts;
reduces total cholesterol
levels
 Sources: olive oil (mono-)
& vegetable oils (poly-)
 Trans: healthy oils that
have been hydrogenated for
products
Saturated Fats
 Stimulate liver synthesis of




cholesterol
Inhibit cholesterol
excretion from body
Increases total cholesterol
Holds all the hydrogens
possible (all single covalent
bonds)
Animal fats
Role of Carbon Dioxide in Breathing Rate
 Of all the chemicals influencing respiration, CO2 is




the most potent and most closely controlled
↑CO2 …hydrated to ↑carbonic acid…↓blood pH
therefore ↑breathing rate and depth to flush out CO2
Remember CO2 is kept in the 40-45 mm Hg range
Hyperventilation designed to remove CO2
↓CO2…respiration is slowed