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dibartola - gautier > Chapter 19 - Disturbances in liver diseases > Flashcards

Chapter 19 - Disturbances in liver diseases Flashcards

1
Q

What does a change in hepatic albumin synthesis affect? (what are the effects of hypoalbuminemia?)

A
  • Oncotic pressure
  • Alterations in renal function
  • Disturbances in production and metabolism of hormones contributing to water, electrolyte, and acid-base imbalances
  • Stimulation of baroreceptors and osmoreceptors leading to changes in effective circulating volume and plasma osmolality
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2
Q

What type of molecules are bile acids?

A

Amphipathic organic anions

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3
Q

Almost all bile acids are conjugated. What are they conjugated to (cats and dogs)?

A

Bile acids are conjugated exclusively to taurine in the cat and to taurine or glycine in the dog

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4
Q

What are the most common causes for the thickening of the bile

A

Stasis of bile flow and dehydration (as water and inorganic electrolytes are absorbed from the gallbladder and biliary ducts)

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5
Q

What mechanisms regulate the canalicular secretion?

A
  • Bile salt-dependent: regulated by bile acid load

- Bile salt-independent: hormones such as glucagon

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6
Q

What are the effects of secretin in the liver?

A
  • Regulates ductular secretion (increase)
  • Influence alkalinization and dilution of bile
    (Secretin initiates expression of a Cl- transmembrane channel and subsequent activation of the Cl-/HCO3- exchanger leading to bicarbonate secretion in ductal bile)
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7
Q

How do bile acid travel from the blood to the bile (mechanisms)?

A

1- Hepatocellular uptake of bile acids is an energy- dependent process linked to sodium transport
2- Protein carriers facilitate cytosolic transport of bile acids to canalicular membranes.
3- Efflux of bile acids into canaliculi via facilitated diffusion dependent on canalicular carrier proteins, an adenosine triphosphate (ATP)-dependent mechanism, or exocytosis of cytosolic vesicles

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8
Q

What is the molecule with the greatest osmotic effects in the canalicular bile?

A

Glutathione [GSH]

–> gives three constituent amino acids (cysteine, glutamate, glycine), yielding three osmolar equivalents

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9
Q

What happens to nitrogens in the liver?

A

Nitrogens are incorporated into glutamate or aspartate in the liver, and then converted into urea (Kreb’s cycle)

https://users.humboldt.edu/rpaselk/C432.S09/C432Notes/C432nLec10.htm

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10
Q

How can albumin be lost from the circulation?

A
  • Through pathologically altered vessels (e.g., vasculitis)
  • Through gut wall (e.g., lymphangiectasia)
  • Through glomeruli (e.g., glomerulo- nephritis, amyloidosis)
  • Into the peritoneal cavity as a result of hepatic sinusoidal hypertension
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11
Q

On an healthy patients, what is the percentage of hepatocytes mobilized to produce albumin (the others are part of the reserve capacity)?

A

Normally, only 20% to 30% of the hepatocytes produce albumin, and synthesis can be increased as needed by a factor of 200% to 300%.

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12
Q

By how much does the production of albumin drop within the first 24 hours after a fast or with consumption of a protein-deficient diet? How fast will we see changes in serum albumin concentration?

A

Albumin production decreases by 50% within 24 hours.

Serum albumin concentration reflects this change only after a lag period ranging from days to weeks.

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13
Q

What are possible causes for decreased albumin production?

A
  • Hepatocellular diseases / Liver failure
  • Fast
  • Consumption of a protein-deficient diet with excessive calories ration
  • Changes in serum oncotic pressure related to hyperglobulinemia and treatment with synthetic colloids
  • Critical illness as part of a negative acute-phase response
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14
Q

How much of the albumin is located extravascularly?

A

In normal animals, 50% to 70% of albumin is located extravascularly, with the largest amounts in interstitial spaces in skin and muscle

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15
Q

What is the half-life of albumin?

A

The half-life of plasma albumin is 7 to 10 days in dogs and 6 to 9 days in cats.

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16
Q

What are the roles of albumin?

A
  • Participates to the oncotic pressure
  • Contributes to the strong ion difference (SID) (strong net negative charge of albumin)
  • Functions as a circulating depot and transport molecule for many ions and metabolites
  • Provides protection against oxidative stress.
  • Plays a role as an anticoagulant, antithrombotic, and antiinflammatory molecule
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17
Q

What are the most common conditions that lead to an acute severe hypoalbuminemia / chronic severe hypoalbuminemia

A
  • Acute: severe extracorporeal loss (e.g. hemorrhage) / aggressive fluid therapy with crystalloids
  • Chronic: PLE / PLN
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18
Q

Where is the majority of nonimmunoglobulin serum globulins synthesized?

A

The majority of nonimmunoglobulin serum globulins are synthesized and stored in the liver

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19
Q

What are the causes for an increase in the synthesis of acute-phase proteins?

A

The synthesis of acute-phase proteins rapidly and markedly increases after tissue injury or inflammation under the influence of cytokines.

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20
Q

What are proposed mechanisms for respiratory alkalosis associated with liver diseases?

A

Respiratory alkalosis in cirrhosis may evolve subsequent to:

  • Reduced arterial oxygen saturation secondary to:
      • Acquired venoarterial shunting
      • Ventilation-perfusion mismatch (derived from ascites-induced restriction of ventilatory efforts or changes in pulmonary capillaries)
      • A shift to the right in the oxyhemoglobin dissociation curve
  • Direct stimulation of the respiratory center by encephalopathic toxins (e.g., NH3)
  • Development of CNS acidosis
  • Compensation for metabolic acidemia
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21
Q

Hypoalbuminemia results in a loss of the buffering capacity of the negative charges on the albumin molecule. What is the calculated base excess (mEq/L) resulting from a decrease of 1 g/dL of plasma albumin?

A

A decrease of 1 g/dL of plasma albumin results in a calculated base excess of 3.7 mEq/L.

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22
Q

What is the most common cause for metabolic alkalosis in dogs with liver failure? In cats with liver failure?

A

Dogs: hypoalbuminemia
Cats: hypochloremia

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23
Q

What are the mechanisms that may contribute to metabolic alkalosis in patients with liver disease?

A 
Hypoalbuminemia
Hypochloremia
Loss of gastric fluid (vomiting)
Diuretics
Blood transfusion (citrate)
Secondary hyperaldosteronemia
Loss of effective extracellular  volume (concentration alkalosis)
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24
Q

In the terminal stage of cirrhosis, which one is the most common? metabolic alkalosis or acidosis?

A

Metabolic acidosis

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25
Q

What are the mechanisms that may contribute to metabolic acidosis in patients with liver disease?

A 
Lactic acidosis (hypoxia + compromised hepatic function/metabolism)
Accumulation of unmeasured anion
Dilutional acidosis
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26
Q

Briefly describe the different steps of lactate metabolism

A

Lactate use is governed by conversion to pyruvate via lactate dehydrogenase (LDH), and the pyruvate formed is either metabolized to glucose or oxidized in the tricarboxylic acid (Krebs) cycle to carbon dioxide and water

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27
Q

What is the Cori cycle?

A

Lactate generation by RBCs, brain, and skin with subsequent gluconeogenesis by liver and kidneys is known as the Cori cycle, an important mechanism of energy provision during starvation.

28
Q

What are the conditions that may increase lactate accumulation?

A 
Hypoxia
Systemic hypoperfusion
Tissue ischemia 
Severe anemia
Cardiovascular insufficiency 
Hepatic failure 
Metabolic alkalosis 
↑ Catecholamines
Thiamine deficiency (PDH cofactor)
Renal failure 
Seizures
Hypoglycemia
29
Q

What is the percentage of lactate metabolized by the liver at rest?

A

40-60%

30
Q

T/F: Reduction in systemic pH compromises hepatic uptake of lactate

A

T: Reduction in systemic pH compromises hepatic uptake of lactate, and decreased hepatic pH arising from lactic acidosis directly disables hepatic lactate metabolism in dogs

31
Q

Why may thiamine deficiency be associated with hyperlactatemia?

A

Thiamine is a cofactor for PDH (pyruvate dehydrogenase) activity

32
Q

What is the loss of functional hepatic mass (%) before we may see clinical signs compatible with hepatic encephalopathy?

A

65 - 70%

33
Q

What are the suspected/possible causes for hepatic encephalopathy?

A
  • Increased ammonia
  • Increased bile acids
  • Increased endogenous benzodiazepines levels
  • Increased GABA levels (g-aminobutyric acid)
  • Increased aromatic amino acids levels
  • Altered neuroreceptors
  • Increased methionine level and toxic metabolites (mercaptans)
  • Increased tryptophan levels
  • Increased glutamine levels
  • Increased short-chain fatty acid levels
  • Increased phenol levels
  • False neurotransmitters (octopamine, phenylethylamines)
34
Q

What are the effects of ammonia leading to HE?

A
  • Increased excitability (if mild increased in NH3)
  • Decreased ATP availability (ATP consumed in glutamine production)
  • Decreased microsomal Na+,K+-ATPase in the brain
  • Disturbed malate-aspartate shuttle: decreased energy
  • Decreased glycolysis
  • Brain edema (acute liver failure)
  • Decreased glutamate, altered glutamate receptors
  • Increased BBB transport: glutamate, tryptophan, octopamine
35
Q

What are conditions that may be associated / precipitate the development of HE?

A
  • Dehydration
  • Azotemia
  • Alkalemia
  • Hypokalemia
  • Hypoglycemia
  • Catabolism
  • Infection
  • PUPD
  • Anorexia
  • Constipation
  • Hemolysis
  • Blood transfusion
  • GI hemorrhage
  • High dietary protein diet
  • Drugs such as benzodiazepines, antihistamines, methionine, barbiturates, organophosphates, diuretic overdosage, phenothiazines, metronidazole
36
Q

What does the liver convert nitrogen to to detoxify?

A

Urea and glutamine

37
Q

Where does urea synthesis occur in the acinar zones?

A

Periportally (Zone 1)

38
Q

Where does glutamine synthesis occur in the acinar zones?

A

Perivenous hepatocytes (Zone 3)

39
Q

T/F: Most NH3 produced in the liver is turned into urea.

A

True

40
Q

T/F: Glutamine is a high affinity, low capacity system that is most important in the face of acidosis.

A

True (urea is the opposite)

41
Q

T/F: BUN is directly affected by hepatic urea synthesis.

A

True

42
Q

Name 3 extrahepatic ways that BUN can be low.

A
  1. Dietary protein restriction
  2. Expanded volume of distribution (hypoalbumin, 3rd space accumulation, splanchnic and systemic vasodilation)
  3. Increased water turnover associated with PU/PD
43
Q

From what two amino acids are creatine derived?

A

Arginine and lysine

44
Q

Where is most creatine located?

A

Muscle (98%, brah)

45
Q

T/F: Total calcium concentration does not predict iCa concentration in dogs.

A

True

46
Q

What are 4 ways that albumin can be decreased in liver failure?

A
  1. Decreased synthesis
  2. Increased distribution into ascites
  3. Malnutrition
  4. Negative acute phase (suppressed by inflammatory mediators)
47
Q

T/F: Hypoalbuminemia in liver disease is generally not accompanied by decreased globulin concentration.

A

True, globs are increased or normal due to a disproportionate increase in alpha globs and acute phase proteins

48
Q

Why do alpha globulins normally increase in liver disease?

A

Increased systemic exposure to gut derived antigens, microorganisms and debris usually removed by the Kupffer cells and presence of inflammatory and immune mediated processes associated with disease

49
Q

All of the following are reasons for hypokalemia in hepatic insufficiency EXCEPT: sufficient energy intake, enteric losses, loop diuretics, secondary hyperaldosteronism, magnesium deficiency.

A

Sufficient energy intake

50
Q

T/F: Correction of hypokalemia can improve CNS function in early HE.

A

True

51
Q

T/F: Hypokalemia arising from diuretics can cause hyperammonemia secondary to metabolic acidosis resulting from renal H+ loss.

A

False, alkalosis

52
Q

In cats with hepatic lipidosis, should you supplement glucose? Why or why not

A

Glucose supplementation is contraindicated in cats with HL because it favors metabolic adaptations that precipitate refeeding syndrome, compromises adaption to fatty acid oxidation, and can potentiate hepatic triglyceride accumulation via enhanced lipogenesis

53
Q

Why is treatment of metabolic acidosis with alkalinizing solutions avoided in patients with signs of HE?

A

alkalosis worsens hyperammonemia and increased NH3 delivery to the CNS

54
Q

Abrupt cessation of lactate metabolism doe snot result in clinically significant lactate accumulation because…

A

of a compensatory increase in lactate extraction by extrahepatic tissues

55
Q

What prognosis are patients with liver disease given when they have a respiratory acidosis?

A

Grave

56
Q

A PA-Pao2 gradient greater than what value warrants consideraton of oxygen therapy?

A

15mmHg

57
Q

Low sodium intake for dogs and cats is less that what value

A

100mg/100kcal energy requirement

58
Q

What is a typical diuretic protocol recommendation initially for ascites

A

loop diuretic (lasix 1-2mg/kg po q12) and an aldosterone antagonist (spironolactone - loading 2-4mg/kg followed by 1-2mg/kg po q12)

59
Q

True or false - Hypoalbuminemia is a dominant factor in the pathophysiology of ascites formation

A

false

60
Q

What type of hypersensitivity reaction can be seen in dogs after a human albumin transfusion?

A

type 3

61
Q

In septic patients, what fraction of an albumin transfusion moves into the interstitial space within 4 hours?

A

up to 2/3 - this promotes interstitial fluid accumulation

62
Q

What are some of the most common complications seen n humans after therapeutic abdominocentesis with liver disease?

A

HE, decreased renal function, hyponatremia

63
Q

when does anemia typically become symptomatic in dogs and in cats?

A

dogs <18%, cats <15%

64
Q

patients with liver disease can often develop a vitamin K responsive coagulopathy - why?

A

this can be related to intestinal malabsorption (secondary to abnormal enterohepatic bile acid turn over), insufficient dietary intake, or impaired enteric synthesis of vitamin K secondary to prophylactic antimicrobial therapy

65
Q

What dose of vitamin K is recommended in liver disease patients?

A

0.5-1.5mg/kg for 2-3 doses Q12, then once weekly

dibartola - gautier (11 decks)

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