This document discusses acid-base balance and the renal regulation of acid-base balance. It provides guidelines for how acids and bases obey the balance principle and how body fluids are buffered. It describes how the input and output of acids can alter bicarbonate levels but not carbon dioxide partial pressure. It explains the independent excretion of carbon dioxide and bicarbonate. It also details the roles of the kidney in regulating acid-base balance through reabsorption and secretion in different tubular segments and production of ammonium ions.

5. Guideline 1:Acids and Bases Obey the Balance
Principle.
Guideline 2: Body Fluids Are Buffered.
Guideline 3: Input and Output of Acids Alter
Bicarbonate But Not the Partial Pressure of CO2.
Guideline4:Excretion of CO2 and BicarbonateAre
Independent of Each Other.

7.  metabolism oF dietary protein.
 metabolism oF dietary weak acids.
 GI Secretions.
 Anaerobic metabolism of Carbohydrate and Fat.

12. Normal contributions of tubular segments to renal hydrogen ion balance:
Proximal tubule
- Reabsorbs most filtered bicarbonate (normally about 80%)*
-Produces and secretes ammonium
Thick ascending limb of Henle’s loop
- Reabsorbs second largest fraction of filtered bicarbonate (normally about 10–15%)*
Distal convoluted tubule and collecting-duct system
-Reabsorbs virtually all remaining filtered bicarbonate as well as any secreted
bicarbonate (Type A intercalated cells)*
- Produces titratable acid (Type A intercalated cells)*
- Secretes bicarbonate (Type B intercalated cells)
* Processes achieved by hydrogen ion secretion.

13. Renal HCO3- Reabsorption Bicarbonate is freely fi ltered at the glomerulus and is reabsorbed
along the nephron through a process involving secretion of H+. Under normal conditions, 100% of
the fi ltered bicarbonate is reabsorbed.

14. Predominant proximal tubule mechanism for reabsorption of bicarbonate.
Hydrogen ions and bicarbonate are produced intracellularly. The hydrogen ions are
secreted via an Na-H antiporter (member of the NHE family), while the bicarbonate is
transported into the interstitium via an Na-3HCO3 symporter (member of the NBC family).
As more sodium enters via the Na-H antiporter than leaves via the Na-3HCO3 symporter,
additional sodium is removed via the Na-K-ATPase.

15. Type A and Type B intercalated cells. A,
Predominant collecting tubule
mechanisms in Type A intercalated cells
for the secretion of hydrogen ions that
result
in the formation of titratable acidity. The
apical membrane contains H-ATPases,
which
transport hydrogen ions alone or in
exchange for potassium.
B, The Type B intercalated cell secretes
bicarbonate and simultaneously transports
hydrogen ions into the interstitium.
The difference between this cell type and the
Type A cell and those in the proximal
tubule is that the location of the transporters
for hydrogen ions and bicarbonate are
switched between apical and basolateral
membranes. ATP, adenosine triphosphate.

16. Excretion of hydrogen ions on
filtered phosphate. Divalent
phosphate (baseform) that has been
filtered and not reabsorbed reaches
the collecting tubule, where it
combines with secreted hydrogen
ions to form monovalent phosphate
(acid form) and is
then excreted in the urine. The
bicarbonate entering the blood is
new bicarbonate, not merely a
replacement for filtered
bicarbonate. ATP, adenosine
triphosphate.

17. Ammoniagenesis and excretion. A,
Ammonium production from
glutamine.
Glutamine is originally
synthesized in the liver from NH4
+ and bicarbonate. When
it reaches the proximal tubule
cells, it is converted back to NH4
+ and bicarbonate.There are more
biochemical steps in the
conversion of glutamine to
ammonium and bicarbonate
than indicated here; only the end
result is shown.

18. B, Ammonium reabsorption in the
thick ascending limb. Ammonium
reaches the thick ascending limb from
two sources. Most comes from
secretion in the proximal tubule.
Some also enters the thin limbs from
the medullary interstitium in the form
of neutral ammonia and is
subsequently reprotonated in the
lumen (ammonium recycling).
Ammonium is reabsorbed in the thick
ascending limb by several
mechanisms,the predominant one
being entrance
via the NKCC multiporter
(where ammonium substitutes for
potassium).

19. C, Ammonium secretion in the
inner medulla. Several
mechanisms are involved.
A prominent one involves uptake
and secretion of neutral
ammonia via specific
transporters in parallel with
hydrogen ion secretion, resulting
in reformation of ammonium in
the lumen. In the innermost
medulla, the high interstitial
ammonium concentration allows
ammonium to substitute for
potassium on the Na-K-ATPase.

20. Summary of renal ammonia
metabolism. The proximal
tubule produces ammonia, as
NH 4 + , from glutamine.
NH 4 + is then secreted
preferentially into the luminal
fluid, primarily by NHE-3. It is
then reabsorbed by the
TAL, primarily by NKCC2. This
results in ammonia delivery
to the distal nephron
accounting for ~20% of final
urinary ammonia; the
remaining ~80% is secreted in
the collecting duct through
parallel NH 3 and
H + transport.
Numbers in red indicate
proportion of total urinary
ammonia present at the
indicated sites under baseline
conditions

21.  Glutamine metabolism and NH4 excretion are
increased during acidosis and decreased during
alkalosis. The signal is unknown.
 Tubular hydrogen ion secretion is
-Increased by the increased blood Pco2 of
respiratory acidosis and decreased by the decreased
Pco2 of respiratory alkalosis.
-Increased, independently of changes in Pco2, by the
local effects of decreased extracellular pH on the
tubules; the opposite is true for increased
extracellular pH

22. -How much bicarbonate is excreted in the urine?
- How much new bicarbonate is contributed to the
plasma by secretion of hydrogen ions that combine in
the tubular lumen with non-bicarbonate urinary
buffers?
-How much new bicarbonate is returned to the plasma
by secretion of hydrogen ions that are excreted as
ammonium?

23. Summary of processes that acidify or alkalinize the blood
Nonrenal mechanisms of acidifying the blood
-Consumption and metabolism of protein (meat) containing acidic or sulfur-containing amino acids
-Consumption of acidic drugs
- Metabolism of substrate without complete oxidation (fat to ketones and carbohydrate to lactic
acid)
-GI tract secretion of bicarbonate (puts acid in blood)
Nonrenal mechanisms of alkalinizing the blood
-Consumption and metabolism of fruit and vegetables containing basic amino acids or the salts of
weak acids
- Consumption of antacids
- Infusion of lactated Ringer’s solution
-GI tract secretion of acid (puts bicarbonate in the blood)
Renal mechanisms of acidifying the blood
-Allow some filtered bicarbonate to pass into the urine
- Secrete bicarbonate (Type B intercalated cells)
Renal means of alkalinizing the blood
- Secrete protons that form urine titratable acidity (Type A intercalated cells)
-Excrete NH4
-synthesized from glutamine

25. High anion gap type
Ketoacidosis
Diabetic
Alcoholic
Starvation
Lactic acidosis
Type A
Type B
D-Lactic acidosis
Intoxications
Ethylene glycol
M ethanol
Salicylate
Pyroglutamic acidosis from acetaminophen
Advanced renal failure

26. Normal anion gap type
I. Gastrointestinal bicarbonate loss
A. Diarrhea
B. External pancreatic or small-bowel drainage
C. Ureterosigmoidostomy, jejunal loop, ileal loop
D. Drugs
1. Calcium chloride (acidifying agent)
2. Magnesium sulfate (diarrhea)
3. Cholestyramine (bile acid diarrhea)
III. Drug-induced hyperkalemia (with
renal insufficiency)
A. Potassium-sparing diuretics
(amiloride, triamterene, spironolactone)
B. Trimethoprim
C. Pentamidine
D. ACE-Is and ARBs
E. Nonsteroidal anti-inflammatory
drugs
F. Cyclosporine and tacrolimus
Renal acidosis
A. Hypokalemia
1. Proximal RTA (type 2)
Drug induced: acetazolamide, topiramate
2. Distal (classic) RTA (type 1)
Drug induced: amphotericin B, ifosfamide
B. Hyperkalemia
1. Generalized distal nephron dysfunction (typ4 RTA)
a. Mineralocorticoid deficiency
b. Mineralocorticoid resistance (autosomal
dominant PHA
c. Voltage defect (autosomal dominant PHA I and
PHA II)
d. Tubulointerstitial disease
IV. Other
A. Acid loads (ammonium chloride,
hyperalimentation)
B. Loss of potential bicarbonate: ketosis
with ketone excretion
C. Expansion acidosis (rapid saline
administration)
D. Hippurate
E. Cation exchange resins

27. Volume-depleted type
Gastric acid loss
Vomiting
Gastric suction
Renal chloride loss
Diuretics
Posthypercapnia
Cystic fibrosis
Volume-replete type
Mineralocorticoid excess
Hyperaldosteronism
Gitelman's syndrome
Bartter's syndrome
Cushing's syndrome
Licorice excess
Profound potassium depletion

28. I . A l k a l o s i s
A. Central nervous system stimulation D-Stimulation of chest receptors
1. Pain
2. Anxiety, psychosis
3. Fever
4. Cerebrovascular accident
5. Meningitis, encephalitis
6. Tumor
7. Trauma
1. Hemothorax
2. Flail chest
3. Cardiac failure
4. Pulmonary embolism
B. Hypoxemia or tissue hypoxia E. Miscellaneous
1. High altitude
2. Pneumonia, pulmonary edema
3. Aspiration
4. Severe anemia
1. Septicemia
2. Hepatic failure
3. Mechanical hyperventilation
4. Heat exposure
5. Recovery from metabolic acidosis
C. Drugs or hormones
1. Pregnancy, progesterone
2. Salicylates
3. Cardiac failure

29. A c u t e :
A i r w a y o b s t r u c i o n t
—aspiration of foreign body or vomitus , laryngospasm , generalized bronchospasm ,
obstructive sleep apnea.
Re s p i r a t o r y c e n te r d e p r e s s i o n
general anesthesia , sedative overdosage , cerebral trauma or infarction,central sleep apnea
C i r c u l a t o r y c a ta s t r o p h e s
— cardiac arrest , severe pulmonary edema.
N e u r o m u s c u l a r d e f e c t s
— high cervical cordotomy , botulism , tetanus , Guillain-Barrй syndrome , crisis in
myasthenia gravis , familial hypokalemic periodic paralysis , hypokalemic myopathy , toxic
drug agents
(eg , curare , succinylcholine , aminoglycosides , organophosphates ).
R e s t r i c t i v e d e f e c t s
— pneumothorax , hemothorax , fl ail chest , severe pneumonitis , hyaline membrane
Disease , adult respiratory distress syndrome.
P u l m o n a r y d i s o r d e r s
— pneumonia , massive pulmonary embolism , pulmonary edema , mechanical
Underventilation.

30. C h r o n i c :
A i r w a y o b s t r u c t i o n :
— chronic obstructive lung disease (bronchitis , emphysema) .
R e s p i ra to r y ce n te r d e p r e s s i o n :
— chronic sedative depression , primary alveolar hypoventilation , obesity
hypoventilation syndrome , brain tumor , bulbar poliomyelitis .
Ne u r o m u s c u l a r d e f e c t s :
— poliomyelitis , multiple sclerosis , muscular dystrophy , amyotrophic lateral
sclerosis , diaphragmatic paralysis , myxedema, myopathic disease (eg , polymyositis ,
acid maltase deficiency ) .
R e s t r i c t i ve d e f e c t s :
— kyphoscoliosis , spinal arthritis , fi brothorax , hydrothorax , interstitial fi brosis ,
decreased diaphragmatic movement (eg, ascites) , prolonged pneumonitis , obesity .

31. II. Acidosis
A. Central
Drugs (anesthetics, morphine, sedatives)
2. Stroke
3. Infectio
B. Airway
Obstruction
2. Asthma
Parenchyma
1. Emphysema
2. Pneumoconiosis
3. Bronchitis
4. Adult respiratory distress syndrome
5. Barotrauma
D. Neuromuscular
Poliomyelitis
2. Kyphoscoliosis
3. Myasthenia
4. Muscular dystrophies
E. Miscellaneous
1. Obesity
2. Hypoventilation
3. Permissive hypercapnia

32. Step 1: assess oxygenation status .
Step 2: Measure pH. This identifies acidemia or alkalemia.
Step 3: Determine partial pressure of CO2 .
Step 4: Determine The change in bicarbonate .
simple or mixed. Calculate the serum anion gap (AG)
Step 5: Determine the cause of the acid–base disorder from
the clinical setting and laboratory tests.
Treat the underlying disorder .

33. pH PaCO2 HCO3
-
normal 7.35 – 7.45 (35–45 mmHg) 22 – 26 mmol l-1
acidotic <7,35 >45 <22
Alkalotic >7,45 <35 >26
Expected PaO2 FiO2 * 5

35. *Metabolic acidosis with compensation
respiratory
*Respiratory acidosis with compensation
kidney
NMetabolic alkalosis
NRespiratory alkalosis


pH
N

PaCO2
Metabolic acidosis
Respiratory acidosis

N
HCO3
-

36. Metabolic and respiratory
alkalosis
Metabolic and respiratory
acidosis
 *
 *
pH


PaCO2
metabolic alkalosis with
compensation respirtory
Respiratory alkalosis with
compenasation kidney


HCO3
-

37.  56 F with vomiting and diarrhea 3 days ago her last
urine output was 12 hours ago .
 BP 80/60 HR 110 RR 28
 Poor skin turgor
NA 130 PH 7,30
K 2,5 P co2 30
CL 105 Hco3 15
BUN 42 Po2 90
CREA 2

38.  Pre-renal azotemia.
 Metabolic acidosis.
 Simple.
 NAG.
 Hydrate + Correct hypokalemia.