DAVENPORT DIAGRAMS:

• Davenport diagrams are graphic displays of acid-base states.
• They illustrate the dynamic relationships between arterial blood pH, bicarbonate and non-bicarbonate buffers, and the partial pressure of carbon dioxide.
• An isopleth represents all possible combinations of bicarbonate and pH values at a given carbon dioxide partial pressure.

4 simple acid-base disorders prior to compensation

Graph Features:

• The x-axis tracks pH; the healthy homeostatic arterial blood value = 7.4
• Values less than this reflect acidosis; values higher reflect alkalosis.
• The y-axis tracks bicarbonate concentration; the healthy homeostatic value 24 millimolar.
• Recall that, as bicarbonate concentration increases, pH becomes more alkaline.
• Isopleth for a partial pressure of carbon dioxide of 40 mmHg.
• A straight line to represent the combination of all non-bicarbonate buffer titration curves.

Disorders that cause the blood to become more acidic.

• Metabolic acidosis occurs when the reduction in bicarbonate concentration lowers the pH.
  • Notice that, because this is a non-respiratory disorder, PaCO2 is unaffected.
• Respiratory acidosis occurs when the lungs retain excess carbon dioxide, so the partial pressure of carbon dioxide is elevated above normal, which lowers the pH. – Recall that respiratory acidosis produces an elevated bicarbonate concentration, which is reflected in our graph.

Disorders that cause the blood to become alkalotic (aka, basic).

• Metabolic alkalosis occurs when bicarbonate concentration is elevated.
  • As in metabolic acidosis, the PaCO2 remains on the 40 mmHg isopleth.
• Respiratory alkalosis occurs when the lungs release too much carbon dioxide
  • Lowers the PaCO2 and increases pH.

Compensatory Mechanisms

• The lungs and kidneys respond to acid-base disorders via compensatory mechanisms that bring pH back to normal.

When metabolic acidosis triggers release of carbon dioxide from the lungs, PaCO2 falls and pH increases.

• Thus, our point of interest lies lower and to the right than on our original graph.
  • Shaded area represents all possible outcomes of partial compensation for metabolic acidosis; the extent of the original disturbance and the magnitude of compensation determine the specific blood outcome.

When respiratory acidosis triggers increased renal excretion of hydrogen ions and conservation of bicarbonate, pH increases.

• The partial pressure of carbon dioxide remains elevated until the source of the disorder is treated, because the lungs are unable to expel CO2.

When metabolic alkalosis triggers respiratory and renal mechanisms to conserve hydrogen ions, pH lowers.

• However, because the respiratory component of compensation requires conservation of carbon dioxide, its partial pressure remains elevated.

When respiratory alkalosis triggers renal mechanisms that conserve hydrogen ions, pH lowers.

• But, until the source of the disorder is treated, the partial pressure of carbon dioxide will remain below 40 mmHg.

Perfect Compensation – Blood pH returned to 7.4

• The blood profile end-states reflect both the original disorders and the compensatory mechanisms.

If the original disorder was metabolic acidosis or respiratory alkalosis, both the bicarbonate concentration and the partial pressure of carbon are reduced (isohydric hypocapnia).

• In the case of metabolic acidosis, this new state is accounted for by:
  • The cause of the disorder, which was a low concentration of bicarbonate
    relative to hydrogen ions.
  • The respiratory component of compensation, which required increased release
    of carbon dioxide.
• In the case of respiratory alkalosis, this new state is accounted for by:
  • The cause of the disorder, which was the excessive release of carbon dioxide, and,
  • Renal compensatory mechanisms that excreted bicarbonate.

If the original disorder was respiratory acidosis or metabolic alkalosis, both the bicarbonate concentration and the partial pressure of carbon dioxide are elevated above normal (isohydric hypercapnia).

• In the case of respiratory acidosis, this is state is accounted for by:
  • The cause of the disorder, which was over-retention of carbon dioxide, and,
  • Renal compensatory mechanisms that conserved bicarbonate.
• In the case of metabolic alkalosis, this state is accounted for by:
  • The cause of the disorder, which was an increased bicarbonate to hydrogen ion ratio
  • The respiratory component of compensation, which required increased carbon
    dioxide retention in the lungs.

Compound Disturbances:

• If both metabolic and respiratory acidosis are in play, pH is reduced more so than if just one disorder was influencing pH; the shaded area shows the range of possible values that could result.
• When alkalosis results from both metabolic and respiratory origins, pH is elevated more so than if only one disorder was present.
  • Be aware that while this information can tell us if there are one or two sources of the pH disturbance, it cannot tell us which preceded the other.

• The enteric viruses we’ll learn about are naked capsids that can withstand harsh stomach acids.
• When symptomatic, illness is characterized by diarrhea and vomiting.
• Outcomes are often worse for children and infants, due to malnutrition and dehydration stemming from fluid and electrolyte loss.
• The causative viruses are transmitted via the fecal/oral route.
• Hepatic viruses cause tissue damage and trigger inflammatory responses that produce the symptoms of infection.

Enteric Viruses

• Cause acute gastroenteritis and are typically ingested via contaminated food and water.
  – Vomiting and diarrhea.
  – Other symptoms include possible fever, nausea, abdominal pain or cramping, and myalgia and malaise.
  – Rehydration and electrolyte therapy are common treatments.
• Key viral causes of gastroenteritis:
  –  Norovirus is a leading cause of gastroenteritis in all age groups in the United States; outbreaks have been associated with contaminated shellfish.
  –  Adenovirus accounts for approximately 15% of hospitalized gastroenteritis cases, especially in infants. Recall that adenovirus also causes respiratory and ocular infections.
  – Astrovirus causes mild, watery diarrhea, most commonly in children.
  However, extra-intestinal infections can occur in immune-compromised patients; some viral genotypes, for example, have been associated with central nervous system infections.
  – Rotavirus is the leading cause of severe diarrhea worldwide in children under five years old; in premature neonates, rotavirus can manifest as necrotizing enterocolitis or hemorrhagic gastroenteritis.
  Because of the high morbidity and mortality associated with rotavirus, vaccination is recommended for all infants.
• In immune compromised patients, particularly AIDS patients and transplant recipients, cytomegalovirus (CMV) and Epstein-Barr Virus are associated with gastroenteritis.
• For a list of bacterial pathogens that induce enteric illnesses, see here.

Hepatic Viruses: Hepatitis Viruses A, B, C, D, and E,

• Hepatitis is characterized by inflammation of the liver.
  – Acute hepatitis = Inflammation that lasts less than 6 months
  – Chronic hepatitis = Inflammation that lasts 6 months or longer
  – In some cases, hepatitis can lead to fulminant liver failure; write that this is characterized by rapid, acute livery injury with hepatic encephalopathy.
• Vaccine availability varies for the hepatitis viruses, and there is no vaccine for Hepatitis C virus due to its heterogeneous nature.

Acute hepatitis

• Hepatitis A, B, C, D, and E can cause acute hepatitis.
• Symptoms include: Jaundice, nausea and vomiting, abdominal pain, dark urine, and joint pain, as well as low or no appetite and fatigue.
  – Liver failure is possible with acute hepatitis, but rare.
• General features of acute hepatitis histopathology:
  – Ballooning degeneration: hepatocytes are unusually large, with a “whispy” look
  – Spotty necrosis throughout the liver tissue
  – Mononuclear cell infiltrate
  – Councilman bodies, which are shrunken, acidophilic cells.

• Hepatitis A and E only cause acute hepatitis, not chronic.
  – Both viruses are transmitted via the fecal-oral route, often via contaminated water.
  – No carrier state for these Hepatitis viruses.
  – Both typically cause mild and self-limiting acute hepatitis; fulminant liver failure is possible but rare.
  – An important exception is that Hepatitis E infection has high mortality rates in pregnant women, especially during the third trimester.

Chronic hepatitis

• Caused by Hepatitis B, D, and C.
• Chronic infections can lead to scarring, cirrhosis, and cancer.
  – Smoking, alcohol use, age, sex, and population seem to increase the risk of disease progression.
• Hepatitis viruses B, D, and C are transmitted via body fluids
  – Carrier states exist
  – Hepatitis B can be transmitted from mother to neonate during childbirth.
  – Hepatitis C often produces extra-hepatic effects, including cryoglobulinemia vasculitis and B-cell non-Hodgkin’s lymphoma, and other immune mediated and inflammation mediated diseases.
  – Hepatitis D is often called the “Delta agent”; though infection with Hepatitis D, alone, does not produce illness, when combined with Hepatitis B, it makes infection worseand increases the risk of Fulminant liver failure.
• Hallmarks of Hepatitis B and C histopathology:
  – Hepatitis B often produces “ground glass” hepatocytes; the tiny grains in the cytoplasm are from viral protein accumulation.
  – Hepatitis C infection is characterized by lymphocyte aggregates and follicles, especially around the portal tracts;
  bile ducts are often damaged, and, steatosis (also called fatty change) can also occur.