Acid-Base & Liver Function Flashcards
acid
substance that can donate hydrogen ions when dissolved in water
base
substance that can accept hydrogen ions
pH
negative log of the H+ concentration
normal body pH
7.35-7.45
normal concentration of H+ in extracellular body fluid
36-44 nmol/L
pKa and how it compares to pH
negative log of the dissociation constant/ionization constant
- pH=pKa: solution is in equilibrium
- pH<pKa: majority of components are protonated because of excess H+
what organs help the body control and excrete H+ to maintain balance?
lungs and kidneys
henderson-hasselbalch equation
pH=pKa + log ([A-]/[HA])
- the interrelationship of the weak acid, conjugate base, and pH
- [A-]=proton acceptor/base
- [HA]=proton donor/weak acid
bicarbonate-carbonic acid buffer system
H2CO3 <-> HCO3- + H+
buffer
consists of a weak acid and salt of its conjugate base; allows solution to resist changes in pH upon adding acid or base
how do the tissues regulate the acid-base balance of the body?
- produces CO2 that diffuses into plasma and rbcs of surrounding capillaries
- CO2 reacts with water and catalyst carbonic anhydrase to form H2CO3
- H2CO3 dissociates into H+ and HCO3- to form concentration gradient
- HCO3- diffuses from rbcs to plasma while Cl- diffuses into rbcs (chloride shift)
- H+ binds with deoxygenated hemoglobin to form deoxyhemoglobin
how do the lungs regulate the acid-base balance of the body?
- O2 diffuses from alveoli into blood and binds with hemoglobin to form O2Hb (oxyhemoglobin)
- H+ combines with HCO3- to form H2CO3
- H2CO3 dissociates into H2O and CO2 for CO2 to be ventilated
- hypoventilation and hyperventilation help regulate the blood pH
what do the kidneys do to help regulate the acid-base balance?
- reabsorbs HCO3- from glomerular filtrate in proximal tubules
**if not reabsorbed, would see markedly increased H+
what is a major mediator of the kidneys’ buffering capacity?
sodium and hydrogen exchange
what happens if the lungs eliminate the CO2 too fast or too slow compared to its rate of production?
- too fast: increased H+
- too slow: decreased H+
what is the respiratory component?
dissolved CO2
what is the metabolic component?
bicarbonate
reference range for pCO2
35-44 mm Hg
reference range for HCO3-
23-29 mmol/L
reference range for pO2
85-105 mmol/L
acidemia/acidosis
when blood pH is less than reference range (<7.35)
- when H+ is increased through increased pCO2 or decreased HCO3-
alkalemia/alkalosis
when blood pH is greater than reference range (>7.45)
- when H+ decreases through decreased pCO2 or increased HCO3-
compensation
the body’s attempt to return the pH toward normal whenever an imbalance occurs
- accomplished by the organ not associated with the primary process
if the imbalance has a metabolic origin, with which organ does the body compensate and how?
lungs respond by altering ventilation by either retaining or expelling carbon dioxide
**compensates immediately but response only short term and often incomplete
if the imbalance has a respiratory origin, with which organ does the body compensate and how?
kidneys respond by selectively excreting or reabsorbing specific ions
**compensates slowly (2-4 days) but response is long term and sustained
mixed acid-base disorders
the presence of more than one process or compensatory mechanism in response to the primary disorder
fully compensated status
pH has returned to normal range with ratio of HCO3-:H2CO3 being 20:1
partially compensated status
pH is approaching normal
uncompensated status
pH is abnormal and body has not started compensating for acid-base imbalance
causes of metabolic acidosis
- overdose of acid-producing substances (alcohols)
- excess production of acidic ketone bodies (diabetic ketoacidosis)
- reduced excretion of hydrogen ions (renal tubular acidosis)
- excessive loss of bicarbonate from diarrhea
causes of respiratory acidosis
- ineffective removal of CO2 from blood (asthma)
- airway obstruction (COPD)
- overdose of drugs that slow respiratory center causing hypoventilation
- decreased cardiac output (congestive heart failure)
causes of metabolic alkalosis
- excessive loss of stomach acid (vomiting)
- prolonged use of diuretics
- excess administration of sodium bicarbonate or excess ingestion of antacids
- hypokalemia
causes of respiratory alkalosis
- high altitudes
- anxiety-induced hyperventilation
- aspirin overdose
- pulmonary embolism or pulmonary fibrosis
respiratory acidosis
- results from decrease in alveolar ventilation (hypoventilation) causing decreased elimination of CO2 by the lungs
- compensated by kidneys excreting H+ and reabsorbing HCO3-
metabolic acidosis
- results from amount of acid exceeding capacity of buffer system and a decrease in bicarbonate
- compensates through hyperventilation
- secondary compensation through kidneys excreting hydrogen ions and reabsorbing bicarbonate ions
metabolic alkalosis
- results from gain in HCO3-
- compensates hypoventilation and increased retention of CO2
respiratory alkalosis
- results from increased rate of alveolar ventilation causing excessive elimination of CO2 by lungs
- compensated by kidneys excreting HCO3- in urine and reabsorbing H+ to blood
conditions for adequate tissue oxygenation
- available atmospheric oxygen
- adequate ventilation
- gas exchange between the lungs and arterial blood
- binding of oxygen onto hemoglobin
- adequate hemoglobin
- adequate blood flow to tissues
- release of oxygen to tissues
oxyhemoglobin (O2Hb)
hemoglobin containing ferrous iron (Fe2+)
deoxyhemoglobin (HHb)
aka reduced hemoglobin; hemoglobin without O2
carboxyhemoglobin (COHb)
hemoglobin bound to carbon monoxide which makes it unavailable for oxygen transport
methemoglobin (MetHb)
hemoglobin unable to bind oxygen because iron is in an oxidized (Fe3+) rather than a reduced state (Fe2+)
four parameters used to assess patient’s oxygen status
- oxygen saturation
- fractional (percent) oxyhemoglobin
- trends in oxygen saturation assessed by transcutaneous and pulse oximetry
- amount of oxygen dissolved in plasma
oxygen saturation
percentage of functional hemoglobin that is saturated with oxygen compared with the total amount of hemoglobin capable of binding oxygen
- measured by pulse oximetry
electrodes
macroelectrochemical or microelectrochemical sensors used to measure pO2, pCO2, pH
which of the following measurement is/are amperometric: pO2, pCO2, pH?
pO2
which of the following is/are potentiometric: pO2, pCO2, pH?
pCO2 and pH
amperometry
reduction of oxygen produces a current that is proportional to the amount of oxygen present in the sample
potentiometry
measures the electrical potential between two electrodes, in which a change in voltage indicates the concentration of each analyte
what type of sample is collected for blood gases?
arterial blood
important notes about handling blood gas samples
- mix tube as soon as possible to prevent clots
- air bubbles will affect results
- must be analyzed within half an hour
- can only be on ice for half an hour or else pO2 will be affected
where does the liver get its blood supply?
hepatic artery and portal vein
major functions of the liver
- excretion/secretion of waste products into bile or blood for excretion
- metabolism of carbohydrates, lipids, proteins, bilirubin
- detoxification of harmful substances
- storage of essential compounds
microscopic anatomy of liver
made up of lobules (functional units responsible for all metabolic and excretory functions of the liver)
two major cell types of the liver
hepatocytes and kuppfer cells
hepatocytes
- make up 80% of the volume of the liver
- perform the major functions associated with liver and are responsible for liver’s regenerative properties
kuppfer cells
macrophages that line the sinusoids of the liver and act as active phagocytes capable of engulfing bacteria, debris, toxins, and other substances
process of excreting endogenous and exogenous substances
substances get excreted into bile or urine with major heme waste product bilirubin
what is the only organ that has the capacity to rid the body of heme waste products?
liver
bilirubin
- principal pigment in bile and heme waste product
- derived from breakdown of red blood cells
what does hemoglobin can degraded into?
heme, globin, iron
how is bilirubin transported to the liver?
unconjugated and bound by albumin
characteristics of unconjugated bilirubin
- insoluble in water
- cannot be removed from the body until it has been conjugated by the liver
- bound by albumin
what converts unconjugated bilirubin into conjugated bilirubin?
uridine diphosphate glucuronosyltransferase (udpgt)
characteristics of conjugated bilirubin
- water soluble
- can be secreted from the hepatocytes into the bile canaliculi
- expelled through the common bile duct to the intestines
urobilingoen
a colorless product or derivative of bilirubin formed by the action of bacteria
what happens to most of the urobilinogen formed?
roughly 80% is oxidized to an organ-colored product known as urobilin (stercobilin) and is excreted in the feces
what are the two things that can happen to the remaining 20% of the urobilinogen?
- absorbed by extrahepatic circulation to be recycled through the liver and re-excreted
- enter systemic circulation and will subsequently be filtered by kidney and excreted in the urine
three ways the liver metabolizes carbohydrates
- use glucose for its own cellular energy requirements
- circulate glucose for use at the peripheral tissues
- store glucose as glycogen within the liver itself or within other tissues
first pass
every substance absorbed in the gastrointestinal tract must pass through the liver before reaching the rest of the body
why is detoxification of waste processes important?
allows important substances to reach systemic circulation and serves as important barrier to prevent toxic or harmful substances from reaching systemic circulation
mechanisms for detoxification
- binds the material reversibly to inactivate the compound
- chemically modifies the compound so it can be excreted in its chemically modified form
where do most detoxifications processes occur?
liver microsomes via the cytochrome p-450 isoenzymes
jaundice
yellow discoloration of skin, eyes, mucous membranes, most often resulting from retention of bilirubin
prehaptic jaundice
when the problem causing the jaundice occurs prior to liver metabolism
common causes of prehepatic jaundice
- an increased amount of bilirubin being presented to the liver
- hemolytic anemia causes an increased amount of red blood cell destruction and the subsequent release of increased amounts of bilirubin for processing
hepatic jaundice
when the primary problem causing the jaundice resides in the liver
hepatic causes of jaundice that result in elevations in unconjugated bilirubin
- crigler-najjar syndrome
- gilbert’s disease
- jaundice of the newborn
hepatic causes of jaundice that result in elevations in conjugated bilirubin
- dubin-johnson
- rotor syndrome
posthepatic jaundice
results from biliary obstructive disease, usually from physical obstructions (gallstones/tumors) that prevent the flow of conjugated bilirubin into the bile canaliculi
cirrhosis
irreversible scarring process by which normal liver architecture is transformed into abnormal nodular architecture
- increased AST/ALT
- increased ammonia
- decreased albumin
signs and symptoms of deteriorating liver function from cirrhosis
fatigue, nausea, unintended weight loss, jaundice, bleeding from the gastrointestinal tract, intense itching, welling in the legs and abodomen
most common cause of cirrhosis
chronic alcoholism
gilbert’s syndrome
characterized by intermittent unconjugated hyperbilirubinemia, underlying liver disease due to a defective conjugation system in the absence of hemolysis
crigler-najjar syndrome
an inherited disorder of bilirubin metabolism resulting from a molecular defect within the gene involved with bilirubin conjugation
dubin-johnson syndrome
a rare, autosomal recessive-inherited disorder where the liver’s ability to uptake and conjugate bilirubin is functional, but the removal of conjugated bilirubin from the liver cell and excretion into the bile are defective
rotor syndrome
an autosomal recessive disease where the proteins that mediate the cellular uptake of compounds are abnormally short, where bilirubin is less efficiently taken up by the liver and removed
neonatal hyperbilirubinemia
a deficiency in udpgt, the enzyme responsible for bilirubin conjugation, because it is one of the last liver functions to be activated in prenatal life since the mother processes bilirubin until birth
reye’s syndrome
- a group of disorders caused by infectious, metabolic, toxic, or drug-induced disease found almost exclusively in children
- characterized by noninflammatory encephalopathy and fatty degeneration of the liver with clinical presentation of profuse vomiting accompanied with varying degrees of neurological impairment
what often precedes reye’s syndrome?
a viral syndrome like varicella, gastroenteritis, an upper respiratory tract infection like influenza
what has strong epidemiological associates with reye’s syndrome?
ingestion of aspirin during a viral infection
what makes up a one-third to one-half of all reported cases of acute liver failure?
drug-induced liver disease
hepatitis type with fecal-oral transmission route
A, E
hepatitis with parenteral transmission route
B, C, D
hepatitis associated with hepatitis b
D
what bilirubin results are measured or calculated?
- measured: total bilirubin and direct bilirubin
- calculated: indirect bilirubin
how to calculate indirect bilirubin?
total bilirubin - direct bilirubin = indirect bilirubin
malloy-evelyn procedure
performed at pH 1.2, bilirubin pigments in the specimen are reacted with a diazo reagents which splits bilirubin into two molecules of azobilirubin which will produce a red-purple color with maximum absorption of 560 nm
jendrassik-grof method
individual fractions of bilirubin are determined by reacting one aliquot with diazo reagent only and reacting another aliquot with diazo reagent and accelerator, caffeine-benzoate
what does caffeine-benzoate do?
solubilizes the water-insoluble fraction of bilirubin and will yield a total bilirubin value
urobilinogen
colorless end product of bilirubin metabolism that is oxidized by intestinal bacteria to the brown pigment, urobilin
what happens to urobilinogen in a normal individual?
excreted in feces and remainder is reabsorbed into portal blood and returned to liver
what does the absence of urobilinogen from the urine and stool often indicate?
complete biliary obstruction
two most common aminotransferases
AST and ALT
what are aminotransferases responsible for?
catalyzing the conversion of aspartate and alanine to oxaloacetate and pyruvate
where are ALT and AST found?
- ALT: mainly in the liver (MORE LIVER SPECIFIC MARKER)
- AST: widely distributed in equal amounts in heart, skeletal, muscle, liver
what is the clinical utility of ALP?
helps differentiate hepatobiliary disease from osteogenic bone disease
what is 5’-Nucleotidase responsible for?
catalyzing the hydrolysis of nucleoside=5’-phosphate esters
gamma-glutamyltransferase
a membrane-localized enzyme used to help differentiate whether elevated ALP levels are due to skeletal or hepatobiliary disease
lactate dehydrogenase
an enzyme released into circulation when cells of the body are damaged or destroyed, serving as a general, nonspecific marker of cellular injury
hemochromatosis
an autosomal recessive disorder leading to abnormally high iron absorption, culminating in iron overload which accumulates in liver, heart, pancreas
- increased serum ferritin
- increased serum iron
- decreased tibc
ceruloplasmin
copper-containing, alpha2-glycoprotein synthesized in the liver
wilson’s disease
an inherited autosomal recessive disorder
- decreased ceruloplasmin
- increased free copper
- increased urinary excretion of copper
laboratory testing for biliary obstruction
- increased ALP
- increased GGT
- increased 5’N
- slightly increased ALT/AST
what condition would AST be significantly increased?
hepatobiliary disorder
