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PHAR 255 Exam 1 > Liver > Flashcards

Liver Flashcards

1
Q

Where is live Located?

A

Located in RUQ of abdomen
2 lobes made up of thousands of lobules

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2
Q

Lobules function:

A

centered on a branch of the hepatic vein (“central vein”)

interconnected by small ducts

contain hepatocytes, separated by sinusoids

“portal triads”at the corners of adjacent lobule–>branches of the bile duct , portal vein, hepatic artery

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3
Q

What is the heaptic duct?

A

Transports bile produced by liver cells to the gallbladder and duodenum

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4
Q

Unique function of liver cells

A

Liver cells can regenerate

About 70% of the liver tissue can be destroyed before the body is unable to eliminate drugs and toxins via the liver

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5
Q

Blood flow to liver

A

~25% of the cardiac output (~1500 mL of blood flow/minute)
Has a dual blood supply

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6
Q

Describe the blood supply flow to the liver

A

venous flow in from the portal vein*
venous blood from the small intestine (absorbed nutrients, drugs, toxins) directly to the liver
pancreatic venous drainage (pancreatic hormones)
spleen (bacteria, byproducts of blood-cell recycling)

arterial flow in from the hepatic artery
liver oxygenation

venous flow out through the hepatic vein
Blood from both portal vein and hepatic artery mixes together in sinusoids and exits the liver through the hepatic vein

Connected to the GI tract via portal veins and bile ducts

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7
Q

Major functions of the liver

A

Excretion
Bile* - produced by hepatocytes; metabolizes cholesterol and fat and detoxifies drugs and toxins

Metabolism
Bilirubin, drugs, nutrients, hormones
CHO, lipids, amino acids, hormones/steroids

Storage
Vitamins/minerals (B12, iron), CHO

Synthesis
Plasma proteins (albumin, coagulation proteins, other transport proteins)

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8
Q

Responsibility of gallbladder

A

Stores and concentrates bile (typically concentrated 5 fold in the gallbladder by absorption of water and electrolytes)

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9
Q

Bile Functions

A

Bile functions:
Emulsification: dietary fat, chol, vitamins
Elimination of waste: excess chol, xenobiotics, bilirubin

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10
Q

contraction of Gallbladder and bile duct is by…..

A

Stimulus (food in duodenum)  Cholecytikinin

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11
Q

What is enetrohepatic recirculation?

A

enterohepatic recirculation (95% of bile acids reabsorbed) – some lost in feces, body makes up for it

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12
Q

What is Bilirubin? What is its metabolism?

A

End product of heme degradation
From breakdown of RBC in spleen/liver
Free bilirubin –> Insoluble-bound to albumin for transport to liver (measured as “indirect bilirubin”)

Bilirubin Metabolism:
Glucuronidated in liver (“direct bilirubin”)
Excreted in bile

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13
Q

Describe billirubin process

A
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14
Q

Liver Dx can be….

A

Can be acute or chronic, focal or diffuse, mild or severe, and reversible or irreversible…

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15
Q

Describe liver damage and the types? Is it reversible?

A

Acute damage to the functional cells of the liver without destruction of the liver’s capacity for regeneration is generally reversible (may be irreversible)

Fulminant liver failure/end-stage disease
insufficient residual hepatocytes to maintain minimal essential liver functionsirreversible

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16
Q

Descirbe the pattern of hepatocellular injury?

A
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17
Q

Etyiology of Hepatic Injury

A

Viruses (HAV, HBV, HCV, HDV, other Epstein bar virus as example )

Drugs (Rx, OTC, herbals)

Environmental toxins (chlorinated pesticides, insecticides, etc.)

Alcohol

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18
Q

What are the two types of hepatic injury?

A

CHOLESTASIS
HEPATOCELLULAR

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19
Q

Define cholestasis.Leads to?

A

A failure of normal amounts of bile to reach the duodenum’

Leads to accumulation of bile in liver cells and biliary passages (intra vs extrahepatic)

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20
Q

Causes of cholestasis

A

Cholelithiasis (gall stones) - most common
Tumor, viral hepatitis, alcohol-related liver disease, drugs
Primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC)

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21
Q

What is primary biliary cholangitis. Stat?

A

Caused by the slow, immune-mediated destruction of small bile ducts within the liver (impaired excretion of bile)

Leading cause of liver transplant in women in Canada

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22
Q

What is primary sclerosing cholangitis?What is it associated with?

A

Involves progressive inflammation and fibrosis affecting any part of the biliary tree

Leads to the progressive destruction of bile ducts

Commonly associated with inflammatory bowel disease

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23
Q

What is choletstaic syndrome? Sx?

A

Blockage of bile flow

Pruritis
Jaundice
Dark Urine
Light coloured stools (greenish)
Steatorrhea (fatty stools)
Xanthoma (growths under skin due to bile salts) and xanthelasma (little growths around the eyelids)
Hepatomegaly

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24
Q

Treatment of choleithiasis?

A

Ursodeoxycholic acid (ursodiol

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25
Q

MOA of Urosodiol

A

Naturally occurring bile acid (bile salt) – small amount endogenously
MOA unclear: decrease chol saturation

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26
Q

How are gall stones formeda nd removed?

A

Gall stones – super-saturation of cholesterol which causes precipitation

  • Eliminated on their own, or they can be removed through laparoscopic surgery
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27
Q

Cholethialisis Urosodiol and Counselling

A

Stones often recur after drug d/c

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28
Q

Urosodiol Dose, A/E

A

Dose is often 250-500 mg BID – take until stones are gone or 1-3 months after

Genrally well tolerated; limited D.I. – may complain of some pruritis

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29
Q

Urosodiol can also be used in…. to…

A

Also used in chronic forms of cholestasis such as PBC or PSC

Improves serum biochemical tests
Limited efficacy in preventing disease progression in PSC

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30
Q

Alternative to ursodiol in PSC

A

Obeticholic acid (OCA) – may use as alternative in PBC
Semi-synthetic bile acid

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31
Q

Pruritis

A

Often associated wit long standing cholestasis
Rule out local cutaneous causes of pruritus such as eczema

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32
Q

Tx of Pruritis Algorithm

A

Cholestyramine (best drug – bile acid sequestrant)
will benefit about 90% of patients; must be continued as long as pruritus is present
Binds to bile salts and prevents reabsorption
Antihistamines

(e.g., hydroxyzine) are of no proven benefit, but their sedative properties may help

Naltrexone (opiod antagonist), rifampin (antibio) or sertraline (anti-depressant)
may be tried if refractory

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33
Q

Hepatiocellular damage definition

A

Direct damage to hepatocytes

Injury may be acute or chronic

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34
Q

Cuases of heaptocellular damage

A

Toxic agents: Alcohol, drugs, toxins
Infections: Hepatitis
Longstanding cholestasis (can lead to hepatocellular injury as well)
Ischemic injury: Thrombosis
Other Diseases (autoimmune, iron overload)

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35
Q

Course of Heaptocellular DamageDepends on n

A

Duration of assault (cells can regenerate)
Intensity of assault (massive: fulminant hepatic failure vs mild to moderate: hepatitis)
Tremendous reserve capacity of liver

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36
Q

When hepatocytes are destroyed, what happens?

A

contents of cells are released into the circulation

functional ability of the liver may be compromised (if enough damage has occurred)

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37
Q

Conditions that can lead to heaptocellular damage?

A

Autoimmune Hepatitis – autoimmune dx characterized by chronic inflammation of the liver with genetic component

Hemochromatosis – excessive absorption of iron; different types; think of inherited type; may be heterozygous and may not know they have; if homozygeous – will develop sx that may be severe – lead to accumulation of iron in liver, hearts, lungs, joints, ect. –> Could lead to liver transpant TX: Phlebotomy (removal of blood once over twice per month initially)

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38
Q

Evaluating liver function iclcudes:

A

Liver Enzyme measurement
Testing for enzymes residing inside hepatocytes (release from damaged hepatocytes)

Liver Function tests (LFTs) - abc’s
Evaluate synthetic capacity of liver
Albumin, Bilirubin, Clotting

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39
Q

Liver enzyme measurement includes:

A

Released into circulation after injury
ALP, AST, ALT, GGT

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40
Q

Liver enzymes measurements are what to liver cells? What do we use them for?

A

Relatively specific to liver cells

When look at pattern to them -Helps to distinguish type of injury.
Cholestatic
Hepatocellular
Other

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41
Q

Indicators of cholestatic injury

A

Liver Enzyme elevations in: ALP & GGT

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42
Q

What is ALp? Where is it found?

A

ALP (Alkaline phosphatase)
Present in bile duct > hepatocytes
High concentrations also found in bone
Marker of cholestatic issues

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43
Q

What is GGt?Also elevated in?

A

GGT (Gamma glutamyl transpeptidase) – non-specific liver enzyme

Elevated in all liver disorders
Confirms hepatic origin of ALP
Also: EtOH, pancreatitis, MI, COPD, renal

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44
Q

Pattern of ALP and GGT

A

Ifr ALP is elevated, but GGT is low –> May not be liver

If elevated with GGT, indicates liver involvement –> More conerned

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45
Q

ASTabd ALt are….

A

Aminotransferases (AST, ALT)
(aspartate aminotransferase, alanine aminotransferase)

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46
Q

Which is more specific, ALT or AST?

A

ALT more specific than AST

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47
Q

Aminotransferases Correlation and Severity

A

Poor correlation with severity, prognosis
May be minimally elevated in cholestatic syndromes (if long enough, may increase by direct toxic insult of hepatocytes)

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48
Q

LDH

A

LDH  (LDH5)
very nonspecific

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49
Q

Benefit of liver enzymes.Disadvantage?

A

often go up before clinical sx goes up so allow for early detection of liver injury – poorly correlated with a severity or prognosis of liver injury

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50
Q

LFT’s measure what?

A

Test the synthetic capability of the liver

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51
Q

Albumin Normal Lifespan

A

20 days

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52
Q

Albumin in liver impairement.Sx?

A

Reduced after sustained assault

Sx: edema, ascites (because you can’t maintain oncotic pressure)
Effects on calcium, highly bound drugs (phenytoin).

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53
Q

When do see albumin decreasing?

A
  • Delay before you see a change in serum albumin following liver injury
  • Sustained assault to the liver – will not see this in acute hepatitis
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54
Q

Bilirubin does what in liver damage? Sx?

A

‘Bilirubin’ (Goes up)
Result of bilirubin retention

Deposits in skin and tissues
Dark urine, pale stools, yellow skin (jaundice)

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55
Q

Causes of Bilirubin increase?

A

Obstruction: Cholestasis
Impaired metabolism: Hepatocellular
Excessive production: e.g hemolytic anemia (increased breakdown of RBC, increase in unconjugated biliiribuin)

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56
Q

Unconjugated Bilirubin

A

Unconjugated bilirubin HIGH – bound to albumin and not soluble in water; measured as indirect

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57
Q

Conjugated by the liver

A

Conjugated bilirubinemia – conjugated by the liver, soluble in the liver, measured as direct

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58
Q

Clootting PT?

A

Liver synthesizes coagulation factors (I, II, V, VII, IX, and X) in excess. Increased bleeding times.

80% of capcity needs to be lost before see a change
- Acute: would not see this as well

Only seen after moderate to significant damage

Note: Vit K deficiency

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59
Q

Big 7 Lab Tests

A
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60
Q

Alcohol Related Enzymes

A

Modest incr <10x

AST>ALT – 2:1

Chronic if albumin low

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61
Q

Define Cirrhosis

A

A chronic diffuse disease characterized by fibrosis and nodular formation

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62
Q

Cirrohosis is a result of…How long to dvelop?Effects the livers ability to what?

A

Result of continuous liver injury

Takes a long time to develop
Overwhelms the body’s ability to regenerate

63
Q

Cirrohosis effect on liver presentation?Leads to?

A

liver becomes hard, shrunken, and nodular

Loss of normal structure and function
Irreversible fibrosis (scarring) – can’t go back as so much scarring (liver transplant)

64
Q

Causes of cirrohos?

A

alcohol, viral, autoimmune, inherited, drugs/toxins, Non-alcoholic fatty liver disease, etc

65
Q

Different types of liver dx??

A

Alcohol-related liver disease (ALD)

Non-alcoholic fatty liver disease (NAFLD); now known as Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Non-alcoholic steatohepatitis (NASH); now known as Metabolic Dysfunction-Associated Steatohepatitis (MASH)

MASLD and increased alcohol intake (MeALD)

66
Q

Guidelines for alchol intake?

A

All levels of alcohol consumption are associated with some risk, so drinking less is better for everyone.

Among healthy individuals, there is a continuum of risk :

Negligible to low for individuals who consume ≤ two standard drinks /wk

Moderate for those who consume between 3 and 6 standard drinks /wk

Increasingly high for those who consume ≥ six standard drinks /wk

67
Q

Recommendations for alcoohol?

A

On any occasion, any level of consumption has risks, and with >2 standard drinks, most individuals will have an increased risk of injuries or other problems

Disproportionately more injuries, violence and deaths result from men’s drinking.

Above low levels of alcohol consumption, the health risks increase more steeply for women than for men.

It is safest not to drink alcohol while pregnant and during the pre-conception period.

For women who are breastfeeding, it is safest not to use alcohol.

68
Q

Are the recommendations specific to alcohol?

A

hese recommendations are to minimize all alcohol-related risks, not just those related to the liver

69
Q

Drink Equivalents

A

12 oz. (341 ml) of beer
12 oz. (341 ml) of a cider or cooler
5 oz. (142 ml) of wine
1 ½ oz. (43 ml) of spirits

70
Q

Alcohol needed for cirrhosis quantity?

A

Metanalysis

No increased risk for occasional drinkers.
Consumption of 1 drink per day in = increased in women, but not men
Drinking ≥5 drinks per day = substantially increased risk in women + men

71
Q

How is cirrhosis diagnosed?

A

Biochemical Marker

Scoring Systems using biochemical marker

Fibrosis-4 (FIB-4) score
helps to estimate the amount of scarring in the liver/risk of fibrosis using age, platelet count, AST and ALT

AST to Platelet Ratio Index (APRI)
Used to estimate liver fibrosis specifically in patients with hepatitis C

Abdominal ultrasound
generally the first imaging modality recommended when liver disease is suspected

Elastography (e.g., FibroScan)
Relatively new, non-invasive way to determine liver stiffness
Measures propagation speed of mechanical waves through liver parenchyma

Limitations = low reliability in patients with obesity, ascites and artificially elevated stiffness due to severe liver inflammation or steatosis

Liver Biopsy
Rarely needed now for diagnosis
Still has a role in definitive diagnosis of underlying cause
Invasive

72
Q

Cirrohsosis results in:

A

↓ functioning liver tissue
impaired function and diminished reserve

Portal HTN (portal-to-systemic shunting)

73
Q

Death Cirrohosis

A

Patients will die ~5-15 years after dx of cirrhosis

74
Q

TX Cirrohosis

A

Of the specific disease
Of the complications (bleeding esophageal varices, ascites, encephalopathy)
Liver transplantation

75
Q

Cirrhosis presnetation types:

A

Compensated, Decompensated

76
Q

Compensated Cirrohosi

A

body functions fairly well despite scarring of the liver

May be asymptomatic

Nonspecific symptoms:
Anorexia, weight loss, weakness, NV, GI upset, muscle wasting
LETs may be abnormal (or normal)

77
Q

Decomensated cirrohosis

A

severe scarring & disruption of function

Symptoms
confusion, edema, fatigue, bleeding

Abnormal LFTs
INR, albumin, bilirubin

Abnormal exam
Signs of chronic liver disease
Portal HTN, ascites, varices, encephalopathy

78
Q

Signs and sx of cirrohosis

A

Asymptomatic
Splenomegaly (enlarged liver)
Jaundice, palmar erythema, and spider nevi (collection of vessels close to the skin)
Ascites and edema
Malaise, anorexia, and weight loss
Encephalopathy (disturbance in brain; accumulation of gut compounds in systemic circulation)
Testicular atrophy, loss of body hair, ammenorrhea, gynecomastia

79
Q

Laboratory findings cirrhosis

A

Hypoalbuminemia
Elevated prothrombin time (PT)
Thrombocytopenia
Elevated alkaline phosphatase (ALP)
Elevated aspartate transaminase (AST), alanine transaminase (ALT), and γ-glutamyl transpeptidase (GGT)
Elevated bilirubin

80
Q

Compplications cirrohois

A

Portal hypertension
Ascites
Spontaneous Bacterial Peritonitis
Hepatorenal syndrome
Varices
Encephalopathy

81
Q

What is the portal system normally?

A

Normally self-contained, low-pressure venous system

82
Q

Describe portal HTN?

A

If blood flow through the liver is obstructed, pressure is increased (“portal HTN”)
Opens “detours” between the portal and systemic circulation
blood is diverted around the liver rather than filtered through the liver
Portal blood bypasses the liver and directly enters systemic circulation (“portal-to-systemic shunting”)

83
Q

What causes portal HTN?

A

Results from increase in resistance to portal flow and increase in portal venous inflow
Splanchnic dilatation
Increase in NO leading to vasodilated state
RAAS

84
Q

Result of portal HTN on vasculature?

A

End up with “back flow” of blood and widening of the venous channels that connect the portal and systemic circulation

85
Q

Portal HTN can lead to….. which can lead to….

A

Spleen enlarges 3-6x
May be uncomfortable/painful to patient

↑ sequestering and destruction of RBCs
Anemia (common finding with someone in cirrhosis but also nutritional deficiencies)
thrombocytopenia

86
Q

Consequences of Portal-to-systemic shunting

A

Portal blood bypassing the liver:

metabolites/toxins in the blood have not been processed by the liver first

↑ sensitivity to noxious substances absorbed from the GI tract (encephalopathy)

malabsorption of fat in the stool (↓ bile flow)

Contributes to all other complications as well: ascites, SBP, varices, hepatorenal sx

87
Q

What is ascites?

A

Collection of fluid in the peritoneal cavity
Many liters may collect (up to 20L +)
Can cause massive distension

88
Q

Pathology of ascites?

A

Hydrostatic pressure
Hypoalbuminemia (reduced oncotic pressure)
Causes relative hypovolemiaaldosterone secretion in response
Renal retention of Na+ and water

89
Q

Patients with ascites should be considred for?

A

Patients with ascites should be evaluated for liver transplant b/c of poor prognosis

90
Q

Aspiration of Ascitic Fluid?

A

Aspiration of ascitic fluid and laboratory analysis is an essential step in the management of patients with newly diagnosed ascites

Review: wbc, total protein concentration and albumin

91
Q

What test can be used to analyze the need for aspiration of ascitic fluid?

A

SAAG (serum-ascites albumin gradient)
= serum albumin – ascitic fluid albumin

If ≥11 g/L indicates portal hypertension
Likely responsive to diuresis

If <11 g/L likely other causes (e.g. infection, malignancy
Not typically responsive to diureses

Total protein concentration
If ascitic>25g/L associated with a SAAG of >11 g/L suggest cardiac dysfunction as the etiology of ascites

92
Q

Goal of management of ascites

A

Remove abdominal fluid
Prevent sx and maintain reasonable QOL

93
Q

Management of ascites

A

Salt restriction
Diureses
Paracentesis
TIPS
Liver Transplant (only true cure)

94
Q

Algorithm for tx of adscites

A
95
Q

For diuresis of ascites, what med is used?

A

spironolactone +/- furosemide
Spironolactone is diuretic of choice here

96
Q

What is paracentesis?

A

Aspiration of peritoneal fluid with a needle

97
Q

Risks and solution with paracentesis

A

Large volume aspiration may result in “fluid steal” from the vascular space – hypovolemia –> acute renal failure

Paracentesis + Albumin may be helpful (often give albumin to maintain oncotic pressure)

May help ↓ discomfort

Risk of abdominal perforation and infection (risk is low; clinicians are good at this)

NOT a cure; will come back  refractory ascites paracentesis on a scheduled basis

98
Q

What is TIPS?

A

Transjugular Intrahepatic Portosystemic Shunt

Create an artificial tunnel through the use of a stent from inflow portal vein and outflow hepatic vein

99
Q

Only cure of ascites

A

Transplant

100
Q

What is no longer recommended for ascites?

A

bed rest no longer recommended
fluid restriction is no longer
recommended unless serum sodium is <120-125 mEq/L (hyponatremia)

101
Q

Spironolactone MOA

A

Inhibits the effects of aldosterone
Generally a weak diuretic and anti-HTN med unless aldosterone levels are ↑

102
Q

Spironlactone Onset

A

Onset generally delayed 3-5 days

103
Q

A/e Spironolactone

A

Hyperkalemia (cause of many DIs)
Dehydration (not common from monotherapy)
Estrogen-like side effects (gynecomastia, decreased libido in males; menstrual irregularities and breast tenderness in females)

104
Q

D.I. Spironolactone

A

DI: Drugs affecting K & may incr digoxin level

105
Q

Furosemide MOA

A

MOA:
Loop diuretic

106
Q

Furosemide A/E

A

Caution with over-diuresis
Potent diuretic: hypovolemia much more common

107
Q

Diuretic Dosing and Titration

A

Usual diuretic regimen consists of a single am dose of spironolactone 100mg & furosemide 40mg od (much lower in HTN, generally this regimen for cirrohosis)

Titrate therapy q3-5d using ratio of 100mg:40mg to max of 400mg spironolactone & 160mg furosemide.

108
Q

Other diuretics qand usage for ascites

A

Metolazone can be added if ascites is refractory to spironolactone and furosemide
Amiloride can be substituted for spironolactone if intolerable side effects

109
Q

Monitoring diuretics for ascitees

A

Monitoring is important!! (watch renal function; risk of hypovolemia, post hepatic renal syndrome)
SCr, Na, K
Weights and blood pressure

110
Q

What is refractory ascites? Prognosis and avoid?

A

Unresponsive to sodium-restricted diet and high-dose diuretic treatment
(400 mg/day of spironolactone and 160 mg/day of furosemide)

Recurs rapidly after a therapeutic paracentesis & high-dose diuretics

Poor prognosis

AVOID NSAIDS

111
Q

Tx refractory ascites

A

serial therapeutic paracentesis, (+/- albumin)
transjugular intrahepatic portasystemic shunt (TIPS),
or liver transplantation

112
Q

Monitoring therapy of ascites

A

Patients should monitor daily weights
Gradual weight loss is the goal
<0.5kg/d if no peripheral edema, more if edema
Edema with ascites; go a bit faster
*Assumes 1kg body wt = 1L of fluid

If no response, check urinary sodium
if low - more diuretic
if high – non-adherence to low Na diet: counsel

Monitor creatinine, serum Na & K frequently
Consider SBP – treatment and prophylaxis (spontaneous bacterial peritonitis)

113
Q

What is SBP? Cause?

A

Infection in ascitic fluid without obvious cause

Thought to be from bacteria translocation (the passage of bacteria from the gut to the bloodstream and other extraintestinal sites, together with decreased host defenses

114
Q

Sx of SBP

A

Sx of fever, chills, abd pain, etc..
Although typical symptoms may be absent

115
Q

SBP Risks

A

Mortality rates are high and presentation is variable so a diagnostic paracentesis should be performed as soon as a patient with ascites and cirrhosis is hospitalized emergently, of has suggestive symptoms

116
Q

Most common bacteria of SBP?

A

E coli, Klebsiella pneumoniae, Streptococcus pneumoniae

117
Q

Tx of SBP

A

Empirically treat:
Culture positive
PMN >250/uL OR a high degree of suspicion for SBP (do not wait for culture if you don’t have one)

Use broad spectrum empiric therapy

Community acquired
Cefotaxime or ceftriaxone x 5 days

Hospital acquired
Piperacillin/tazobactam
meropenem±vancomycin
Albumin infusions may be added as well

118
Q

Monitoring of EMpirirc Anti-bio for SBP.Clinical Response?

A

Second ascitic fluid collection recommended 48h after initiation

Clinical response=decrease in PMN count by 25%

119
Q

Prophylaxis of SBP. WHich ones?

A

Consider prophylaxis for pts having survived an episode of SBP (secondary prophylaxis), or those at high risk (primary prophylaxis)

(High risk= low ascitic fluid total protein ascites or variceal hemorrhage)

ex: norfloxacin, septra or ciprofloxacin

120
Q

After SBP, pt should be considered for:

A

Patients should be referred for liver transplant if eligible after experiencing SBP

121
Q

What is hepatorenal syndrome?Due to?

A

Renal failure in patients with severe liver dz

Characterized by severe vasoconstriction of the renal circulation (activation of RAAS)

122
Q

In hepatorenal, would see kidney changes?

A

No pathologic changes are identifiable in the kidney (due to hemodynamic changes)

renal abnormalities associated with liver disease are functional (usually improve with transplant)

123
Q

When does hepatorenal syndrome occur?

A

Typically occurs in patients with massive, tense ascites
may be precipitated by aggressive diuresis or SBP

124
Q

Tx Hepatorenal Syndrome

A

Stop diuretics

Avoid all potential nephrotoxins such as NSAIDs & aminoglycosides

125
Q

What are varices?

A

High pressure in portal vein

Creates “bypasses” or shunts (collaterals – collateral veins)

Relatively small veins become engorged with an excess of blood (Varices)

126
Q

Principal sites of varices

A

Veins in rectal area (hemorrhoids)
Abdominal wall (umbilicus)
Esophageal varices (Most common here)

127
Q

Esophogeal Veins rates

A

65% of patients with advanced cirrhosis

Veins become enlarged and tortuous (twisted)

Can easily rupture causing massive bleeding

Complicated by clotting disorders
Causes massive hematemesis

7-15% mortality

128
Q

Risks of esophogeal varices?

A

Very difficult to stop the bleeding
High risk of recurrent hemorrhage
Possible prophylaxis (primary/secondary prevention)

129
Q

A variceal bleed is an….;

A

acute medical emergency

130
Q

Tx Goals of variceal blees

A

Adequate blood volume resuscitation
Protection of airway from aspiration of blood
Prophylaxis against SBP and other infections
Control of bleeding
Prevention of re-bleeding
Preservation of liver function/prevention of hepatic encephalopathy
Prevention of acute kidney injury

131
Q

Treatmennt of variceal bleeds

A

Packed red blood cells
To resuscitate blood volume
Goal hemoglobin 70-90g/L

Antibiotic prophylaxis for SBP
greater chance of infection with bleeding
Ceftriaxone, cipro, septra, norfloxacin (during acute event)

Octreotide or somatostatin IV

Vasoconstrictors which decreased splanchic blood flow
Used to stop or slow bleeding
Can be discontinued once free of bleeding for at least 24 hours (ICU tx setting)

Endoscopic therapies
band ligation
More effective > control of hemorrhage, less risk for rebleeding, decreased likelihood of adverse events, decreased mortality) – tie off the bleed with band
Sclerotherapy – inject sclerosing agent into the vein to stop it from bleeding by endoscope –>Gastric varices

TIPS
For those who fail to achieve or maintain hemostasis despite combined endoscopic and pharmacologic therapy

132
Q

Prevention of variceal bleed?

A

Prophylaxis should be given to

Patients with small varices + increased risk of bleeding

Child Pugh C (severe cirrhosis), Portal pressure >12mmHg

Previous bleed, continued alcohol use

Patients with medium/large varices

133
Q

Non-selective beta-blocker examples

A

Propranalol and Nadalol

134
Q

MOA of Nadalol and Propranalol

A

decreased portal venous pressure via
decreased cardiac output
unopposed alpha vasoconstriction leading to arteriolar splanchnic vasoconstriction

135
Q

Effectiveness of Non-selective beta-blockers

A

Reduces bleeding incidence by up to 50%
Portal pressure <12mmHg?

136
Q

Sqafety Non-selective ebta-blockers

A

Asthma (beta-agonsists), mask sx diabetes
Beta blocker s/e
Refractory ascites (watch hypotension)

137
Q

Nadalol Dosing Regimen

A

Initial 20mg OD
- Max: 240mg/day (or 120mg with ascites)
- Titrate q3-4 days
- Minimal CNS effects
- 70% excreted unchanged (primarily renally unchanged)

138
Q

Propranalol Dosing regimen

A

Initial 20mg BID
- Max: 320mg/day (or 160mg with ascites)
- Titrate q3-4 days
- 0.5% excreted unchanged (1A2 substrate)

139
Q

Titration of betablocker

A

***Titrate Bbl to 25% decrease in resting HR or pulse 55bpm

140
Q

Prevention of Variceal bleeding primary and secondary

A

Primary prophylaxis:
Non-selective beta blockers
EVL
May be preferred if high risk of bleed, refractory ascites, SBP

Secondary prophylaxis:
Non-selective beta blocker + EVL
TIPS for those who have re-bleeding despite therapy

141
Q

What is hepatic encephalopathy?

A

CNS dysfunction observed in late-stage cirrhosis

142
Q

Cause of encephalopathy?

A

Accumulation in the bloodstream of neurotoxic substances that are normally removed by the liver

MOA not entirely clear but a number of substances have been implicated

Ammonia pathway (treatment targeted here as of rn)
Tryptophan pathway
GABA’ergic compounds pathway

143
Q

Encephalopathy Presentation Stages

A

Grade 1:
Changes in behavior, mild confusion, slurred speech, disordered sleep
Mild Tremor, anxiety, impaired hand writing

Grade 2:
Lethargy, moderate confusion
Ataxia, asterixis, personality changes

Grade 3:
Marked confusion (stupor), incoherent speech, sleeping but arousable
Seizures, muscle twitching, delirium, bizarre behavior

Grade 4:
Coma, unresponsive to pain

144
Q

Management of encephalopathy started when?

A

Be alert for signs and symptoms
Confusion, drowsiness, asterixis

Treatment should start ASAP if symptoms appear

145
Q

Management of encephalopathy?

A

identify and correct precipitant
restrict dietary protein (and then re-add once tolerated)

avoid CNS depressants ex: BZD

most therapies aimed at lowering blood ammonia []’s
lactulose, antibiotics
Other

146
Q

What is lactulose?

A

Synthetic disaccharide (galactose + fructose)
Not absorbed in the gut(can be used in diabetes)

147
Q

MOA of lactulose

A

Degraded by colonic bacteria to formic, acetic, and lactic acids
Reduces pH reducing ammonia absorption, decreases production of urease-producing bacteria
Reduces GI transit time

First line (cheap, readily available, safe except for diarhhea)

148
Q

Dosage of Lactulose. Onset?

A

Dosage: (15ml=10g lactulose)
15-45ml tid-qid
Onset 12-48 hours

149
Q

MD of Lactulose

A

Maintenance dose: 2-3 soft formed stools/day (or less if mental status improves at a lower dose)
Can ↓ dose once mental state improves, often d/c within days to weeks (rarely may see long term usage)

150
Q

Lactulose Tolerance

A

Very sweet (fruit juices or pop may help)
GI: Nausea, gas, bloating, diarrhea

151
Q

Alternatives to lactulose?

A

Metronidazole
Sterilizes GI tract & inhibits activity of urease-producing bacteria, decreasing production of ammonia
Limited used due to adverse effects (e.g. peripheral neuropathy associated with long term use)
Bacterial resistance

Rifaximin
non-absorbable derivative of rifampin (MOA as above)
at least as effective as lactulose, but costly
Used in com bo with lactulose

152
Q

Cirrohosis Gneral Approach

A

Discontinue alcohol (higher risk; bleeding, medical emergency) – may help improve reversible sx

Avoid ASA/NSAIDS
may contribute to gastritis or GI bleed
blunting diuretic effects in ascites

Avoid sedatives/narcotics if possible

Adequate nutritional intake

Deficiencies are common

153
Q

Nutritional Deficiences in Liver DX

A

Protein calorie and micronutrient deficiencies are common
Multifactorial
Decreased dietary intake
Malabsorption/Digestion

Overall loss sof protein ADEK vitamins

154
Q

N=Deficiences with hevay alcohol use

A

Thiamine (vitamin B1)
Deficiency–> Wernicke’s Encephalopathy

Prevention:
200mg/day (oral)

Pyridoxine (vitamin B6)
Supplementation of 2mg od suggested

Folate
Supplementation of 400 ug od suggested

Consider multivitamin

PHAR 255 Exam 1 (8 decks)

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