Week 10: liver diseases Flashcards
what are the 2 sources of blood flow to the liver?
- oxygenated blood flows in from the hepatic artery (25% blood supply)
- nutrient-rich blood flows in from the hepatic portal vein (75% blood supply)
- hepatic portal vein located in the abdominal cavity
- channels blood from the GI tract and spleen -> capillary beds in the liver
what is the sources of blood flow out of the liver
hepatic vein drains blood back to the heart from liver to Inferior Vena Cava
hepatice portal vein - deoxygenated from intestines
whats the only vein that takes blood back to the heart
hepatic vein takes blood back to the heart
R sided HF causes back up and increased pressure in the hepatic vein and liver. causes congestion in the liver and impacts blood supply into the liver as well. congestion of blood flow also causes portal hypertension.
can the liver regenerate/cells regenerate
yes! however this process can get damaged (i.e fibrosis)
thru cellular replication
is the liver usually a low or high pressure system
low - so with inflammation/portal hypertension this can lead to increased pressure and varices and other abnormalities
R sided HF failure causes what to the liver
will cause congestion in the liver
what does the liver produce/what is it required for
- bile
- proteins for blood plasma
- coagulation factors
- immune factors
- carbohydrate, protein, and fat metabolism
- clears blood of: drugs, toxins, bacteria
- conjugates bilirubin
- processes hemoglobin for use of its iron content
- ammonia -> urea
- storage
bile
helps with digestion, breaks down fats to fatty acids
what protein does the liver produce
albumin
if coagulation factor in liver is damaged what happens
unlikely to clot, at risk for bleeding
when our liver is not functioning what builds up
drugs, toxins, bacteria and have a negative impact on our bodies function
what happens with unconjugated bilirubin if the liver does not do this
not water soluble, cannot be filtered by the kidneys, and is not excreted therefore in urine
what sys does elevated ammonia impact most
neuro!
what can the liver store
- glucose in the form of glycogen
- fat soluble vitamins
- water soluble vitamins
- minerals like iron and copper
- folic acid
- fatty acids
- beta globulin
what is hepatitis
- inflammation of the liver
- most often caused by a virus (A, B, C, D, E, and G) - focus on A, B, C
other causes: - chemicals and drugs: alcohol
- autoimmune disorders
- metabolic disorders
- genetic abnormalities - wilson’s disease, hemocromatosis, biliary cirrhosis
- rarely bacteria
what is wilson’s disease
copper metabolism problem -> liver cell damage from copper
what is hemochromatosis
iron absorption dysfunction
what bacteria usually affect the liver
streptococci, e. coli, salmonella
what happens in hepatitis
- widespread inflammation of liver tissue
- attacks the liver cells specifically - invaded and marked by virus, immune system begins to attack cells and snowballs into cell death and liver inflammation
- spreads into the bloodstream: fever, rash, malaise
what is the damage in acute infection of hepatitis mediated by
cytotoxic cytokines and natural killer cells
what happens in acute infection from hepatitis
- lysis of infected hepatocytes
- liver cell death (necrosis)
- results in inflammation of periportal
- liver cells can normally regenerate through cellular replication, but this may be impaired through cellular replication but this may be impaired if liver cell loss is massive
- immune-complex reaction -> rash, angioedema, arthritis, fever, malaise
clinical manifestations of acute phase of hepatitis
- maximally infective
- lasts from 1-4 mo
- mostly GI symptoms
- may have no symptoms (30% with acute hepatitis B, 80% with acute hep C)
- immunosuppressed may also have no symptoms
clinical manifestations of chronic phase of hepatitis
- begins as jaundice is disappearing
- lasts wks to mo
- many chronic pts are asymptomatic
- major complaints: malaise, easily fatigability, myalgia and arthralgia, hepatomegaly
which of the heps are more likely to result in chronic disease
hep b and c
almost all cases of hep A resolve without progression to chronic phases
does the absence of jaundice in chronic phase hepatitis mean recovery?
absolutely not
s/s pts complain of with hepatitis
- anorexia
- n/v
- RUQ discomfort/pain
- constipation or diarrhea
- altered taste and smell
- fever
- malaise
- headache
- arthralgia
- urticaria
- hepatomegaly
- splenomegaly
- wt loss
- jaundice
- pruritus
- dark urine
- light stools
- fatigue
- distaste for food, alc, cigs
what causes hepatitis dark urine and light stools
bilirubin
why do pts w hepatitis get itchy
from bile build up
state the different 3 tests for pts suspected with hepatitis
- viral serological tests
- antigens and antibodies - serum liver enzymes
- determine injury to liver vs. bile duct
- AST & ALT liver cell injury
- ALP & GGT: bile duct injury - liver function tests
- albumin, bilirubin, prothrombin time (INR)
what do serological tests show
can differentiate the diff btwn types of hepatitis
antigens and antibodies
what does AST & ALT show us
are released w liver damage (similar concept to cardiac enzymes)
what does ALP & GGT show us
are injured to a lesser extent until the liver function caused bile back up
bile duct injury
how is hep A transmitted
- ingestion of contaminated food and water, often acquired by travellers, infectious for 28 days.
- most infective in the 2 wks before symptoms, and remain so for 1-2 wks
- fecal-oral
transmission of hep b & c
- contact w infected bodily fluids
- sharing of contaminated needles (IV drug use/needle stick injury/tattoos)
- mom to baby during birth
- sexual transmission
- blood transfusions before 1985
- hep b: infectious before and after symptoms appear about 4-6 mo, and infectious for life if they are a carrier
- hep c: infectious 1 wk prior to symptoms occurring, and continues thru the clinical course - 70% of people develop chronic hep c and remain infectious for life
whats albumin levels like w normal functioning liver
normal to high (35-50g/L)
when diseased liver what happens to bilirubin
levels rise bc liver metabolizes the bilirubin
who should get tested for hep a
- pts w onset of prodromal s/s (n, anorexia, fever, malaise, abdo pain) and jaundice or elevated serum aminotransferase levels, particularly in the setting of known risk factors for hep a transmission
- travellers to places w high levels, drug use, crowded conditions, poor personal hygiene, sexual contact
who should get tested for hep b
- s/s of acute or chronic hepatitis
- asympt pts who are at high risk exposure to HBV
- unvaccinated, previous HBV that continue to engage in high-risk behaviours (rescreen q1-2 yrs)
- birth places w higher prevalence, preg women, needle use, immunosuppressed ppl, infants w infected mother, drug use, sexual activity w infected partner, end stage kidney disease, inmates, close-contact/household
who should get tested for hep c
one time screening for all adults and repeat for those w ongoing risk
- drug use, sexual activity, blood transfusions before 1985, inmates, etc
how do we
1. prevent
2. manage acute:
3. manage chronic
hep a
- vaccine IVIG. good hygiene and safe food/water.
- usually no hospital admission. mainly supportive. full recovery within 2-3 mo max 6 mo latest usually. 10% become sick again at 6 mo following acute illness.
IVIG works for 6-8 wks, passive immunity. - N/a
how do we
1. prevent
2. manage acute:
3. manage chronic
hep b
- vaccine, IVIG
- supportive management > 4 wks antiviral. low risk for liver failure. many no symptoms. spontaneous resolution. antiviral meds for symptoms longer than 4 wks. goal is to suppress viral load and normalize liver enzymes and slow disease prevention. worried about cirrhosis and liver failure.
- monitor liver function for signs of worsening condition. cannot be cured, no antivirals (rarely used) for chronic hep B. delaying and managing progression of liver disease.
how do we
1. prevent
2. manage acute:
3. manage chronic
hep c
- no vaccine. modify high risk behaviours.
- supportive management. treatment delayed x12 wks. ~50% cases clear spontaneously. rarely results in liver failure.
- monitor liver function for signs of worsening condition. antivirals. can be completely cured. more likely to cause long-term damage.
meds - many have side effects have brutal side effects.
what meds can be taken for hep c
interferons (boosts immunity in viral infection), ribaviran (stops viral replication) DAA (kills virals), protase inhibitor (slows multiplication), direct inhibitors.
know the basic mechanisms in the text!
what is our symptomatic care for hepatitis
- ensure adequate nutrition
(antiemetics: metoclopramide, small frequent meals) - headaches/arthralgias: mild analgesics
- pruritus: benadryl
- adequate rest
+ assess liver function and appropriate screening
prevent re-infection
pt education for hepatitis
- home directions, assessment of symptoms
- transmission risks - safe needle handling
- immunization for hep A and B
which types of hepatitis have vaccines?
A and B
when is non-alcoholic fatty liver disease (NAFLD) determined and what can it progress too
determined when no other causes for secondary hepatic fat accumulation (ex: heavy alcoholic consumption) are present
ranges from asympt to signs of severe liver disease
can progress to severe liver inflammation and fibrosis (cirrhosis)
steatosis =
fatty built up
2 subdivides of NAFLD just state
- non-alcoholic fatty liver (NAFL)
without inflammation - nonalcoholic steatohepatitis (NASH)
with inflmmation
non-alcoholic fatty liver (NAFL)
hepatic steatosis is present w/o evidence of significant inflammation
nonalcoholic steatohepatitis (NASH)
hepatic steatosis is associated w hepatic inflammation
in NAFLD what causes liver inflammation and damage
buildup of fat in the liver - at risk for advanced fibrosis
what modifiable risk factor is linked to fatty liver disease
obesity
what are the AST ALT and ALP levels like in NAFLD
liver enzymes elevated
AST/ALT 2-5x upper limit. ALP 2-3x.
what are albumin and bilirubin like in NAFLD
usually norm unless cirrhosis has developed
NAFLD can also present w signs of liver failure what are s/s of this
- fatigue, malaise, vague pain in the abdomen RUQ
- enlarged liver and enlarged spleen
- jaundice occurs late and is an indication of severe liver disease
- as disease progresses reduced albumin and increased bilirubin and INR, thrombocytopenia, neutropenia (low platelets and neutrophils in late stage_
overall NAFLD usually have one or more component of the metabolic syndrome
advanced fibrosis =
cirrhosis
how do we diagnose NAFLD
- hepatic steatosis by imaging or biopsy
- exclusion of significant alcohol consumption or other causes
- absence of co-existing chronic liver disease
how do we manage NAFLD
no definitive treatment is available*
1. reduce risk factors
- treat diabetes, wt loss, cholesterol, elimination of harmful meds
- wt loss (bariatric sx, drug tx)
- maintain healthy wt, diet, and exercise
- limit alc intake
2. immunizations (hep a and b)
3. rarely - vit E - improves steatosis and inflammation
4. when liver fails - liver transplant
*monitor enzymes every 3-6 mo to track progress of disease
age common for cirrhosis
40-60 yrs of age
is cirrhosis more common in men or women
twice as common in men
how is cirrhosis characterized
- by fibrosis (scar tissue) and conversion of normal liver architecture to abnorm nodules
(overgrowth-lobules irregular-impede blood flow) - irreg and disorganized regeneration, poor cellular nutrition and hypoxia = decreased liver function
- progression of liver injury to cirrhosis may occur over wks to yrs
- final stage of chronic liver disease
- potentially reversible-fibrosis regression in early stages
- impedes blood flow - increased pressure in vascular sys
- poor cellular nutrition and oxygenation
- can take wks-yrs
common causes of cirrhosis
- chronic viral hepatitis (hep b, c)
- alcoholic liver disease
- hemochromatosis (hereditary)
- nonalcoholic fatty liver disease
what is alcoholic cirrhosis
- alc has a direct hepatotoxic effect
- from both alc and associated malnutrition
- accumulation of fat cells in the liver
- leads to widespread scar formation
- most common cause of cirrhosis
- controversy-alcohol or malnutrition
- combo of chronic hepatitis and excessive alc use accelerates the degree of liver damage
- most common cause of necrosis
describe compensated clinical manifestations of cirrhosis
- liver is able to continue to function
- often no s/s
- liver tests are normal in compensated cases
describe decompensated clinical manifestations of cirrhosis
one or more complications present - cirrhosis occurs
describe compensated clinical manifestations of cirrhosis early s/s
- can be asymptomatic
- onset usually insidious
- abdo pain
- weakness
- fever
- lethargy/fatigue
- wt loss
- enlarged liver or spleen
describe decompensated clinical manifestations of cirrhosis early s/s
- s/s can be abrupt
- GI disturbances: n/v, flatulence, changes to bowel habits, anorexia
- jaundice
- pruritus
- skin lesions (spider angiomata)
- endocrine disturbances
- hematological problems
- ascites/edema
- confusion from high ammonia levels (encephalopathy)
- gynecomastia
- hepatomegaly
- hepatocellular failure
- portal vein hypertension (blood from GI - liver and spleen)
describe clinical manifestations of cirrhosis late s/s - jaundice
- jaundice
- decreased ability of liver cells to conjugate and excrete bilirubin
- minimal or severe, depending on liver damage
- functional derangement of liver cells
- if obstruction of the biliary tract occurs, obstructive jaundice may also occur and is usually accompanied by pruritus: caused from accumulation of bile salts underneath the skin
describe clinical manifestations of cirrhosis late s/s - skin manifestations
- spider angiomas
- small dilated blood vessels
- most frequently found on the trunk, face, and upper limbs
- believed to result from alterations in sex hormone metabolism - palmar erythema
- red area that blanches w pressure
- increased circulating estrogen
cant metabolize steroid hormones
describe clinical manifestations of cirrhosis late s/s - endocrine disorders
- steroid hormones (adrenal cortex, testes, ovaries) metabolized and inactivated by the normal liver
- damaged liver - unable to metabolize results in various manifestations
- increase estrogen levels
- amenorrhea or vaginal bleeding in older women
- high aldosterone - sodium and water retention, potassium loss
describe clinical manifestations of cirrhosis late s/s - peripheral neuropathy
dietary deficiencies of thiamine, folic acid, and cobalamin (vit B12)
describe clinical manifestations of cirrhosis late s/s - hematological manifestations
- splenomegaly
- from backup of blood from portal vein into spleen
- thrombocytopenia, leukopenia, anemia - bleeding tendencies
- decreased production of hepatic clotting factors
low platelets indicate cirrhosis
cirrhosis diagnostic studies
- hx and physical exam
- lab tests (liver enzymes, lytes, WBC, RBC, platelets, PT/INR, albumin, stool for occult blood, analysis of ascitic fluid)
- liver imaging - U/S, MRI, CT
- liver biopsy
for liver enzyme (AST, ALT, ALP, GGT)
1. what is the result and
2. rationale for cirrhosis
- increased
- released from damaged liver cells and bile duct
for lytes for cirrhosis
1. what is the result and
2. rationale for cirrhosis
- increased or decreased
- malnutrition and poor absorption
for WBC for cirrhosis
1. what is the result and
2. rationale for cirrhosis
- decreased
- splenomegaly
for RBC for cirrhosis
1. what is the result and
2. rationale for cirrhosis
- decreased
- splenomegaly, poor diet, poor absorption of folic acid, bleeding from varices
for platelets for cirrhosis
1. what is the result and
2. rationale for cirrhosis
- decreased
- splenomegaly
for PT/INR for cirrhosis
1. what is the result and
2. rationale for cirrhosis
- increased
- lack of clotting factors
for albumin
1. what is the result and
2. rationale for cirrhosis
- decreased
- liver unable to produce proteins
cirrhosis management
- slow or reverse progression of disease
- preventing superimposed insults to the liver
- identifying meds that require dose adjustments or should be avoided entirely
- managing symptoms and lab abnormalities
- preventing, identifying, and treating the complications of cirrhosis
- determining the appropriateness and optimal timing for liver transplantation
avoid/adjust meds that require liver to metabolize
list 7 cirrhosis complications
- portal HTN
- esophageal and gastric varices
- peripheral edema and ascites
- hepatic encephalopathy
- hepatorenal syndrome
- spontaneous bacterial peritonitis
- hepatocellular carcinoma
what are varices
dilation/stretching of veins
what is portal HTN
- elevated pressure in the portal vein
- collateral circulation develops in an attempt to:
1. reduce high portal pressure
2. reduce the increased plasma volume and lymphatic flow
3. common areas for collateral circulation
a) lower esophagus, anterior abdominal wall, the parietal peritoneum, and the rectum
b) esophageal and gastric varices, caput medusae and hemorrhoids may develop
4. normal portal pressure is 5 to 10 mm Hg
5. bleeding >12 mmHg - 2 veins going in, one going out bleeding is an emergency
- structural changes to liver compress and damage the portal and hepatic vein, obstruct blood flow
- pressure = venous inflow and resistance to outflow of portal venous system
caput medusa
varices around the umbilicus - distention of epigastric veins
portal HTN collaborative care
- nonselective β-blockers (propranolol, nadolol)
- nitrate-isosorbide mononitrate
- combined long-term endoscopic and drug therapy
- transjugular intrahepatic portosystemic shunting (TIPS) or portacaval shunt
- prevent bleeding is the primary goal
- choose beta blockers that inhibit beta 2 receptors to decrease portal and collateral blood flow
- nitrates for vasodilation
- endoscopic treatments - ligation at the base of the varices to limit pressure and bleeding
TIPS procedure
- catheter from jugular punctures hepatic vein and goes to the portal vein, stents extend that whole way
- redirects blood flow from portal sys to reduce pressure
- increases risk of hepatic encephalopathy from ammonia - not getting metabolized through the liver
esophageal and gastric varices
- complexes of tortuous veins, enlarged and swollen as a result of portal HTN
- location
a) esophageal (80%) - distal esophagus
b) gastric (20%) - gastric fundus - contains little elastic tissue and are fragile
- can rupture, causing sudden, catastrophic GI bleeding
- contributing factors
a) alc ingestion, poorly masticated foods, coarse foods, acid regurg from stomach, increased intra-abdo pressure - pt may have melena or hematemesis (assess Hgb)
low Hgb + bleeding = bad
1/3 turn into hemorrhage
serious and common complication
varices collaborative care minus drug therapy
goal is to prevent bleeding!
- risk factors for esophageal bleeding include:
- variceal size
- decreased wall thickness
- degree of liver dysfunction - preventative strategies
- avoid alc, ASA, NSAID’s and irritating foods
- resp infection promptly treated
- meds to reduce pressure in the portal vein: nonselective β-adrenergic blockers (ex: propranolol or nadolol) - if bleeding occurs stabilize pt, manage airway, provide IV therapy
- endoscopic therapies
- sclerotherapy
- ligation of varices (banding)
- shunt therapy (more common after 2nd bleed) - balloon tamponade
- controls hemorrhage by compression of varices
- prevention and control
- increased size = bleeding risk
- control coughing and other things increasing abdo pressure
what is sclerotherapy
clots the distended vein
what to do if varices start bleeding
stabilize first - airway, IV fluids, blood products
varices interventions during active bleeding
- admin of blood products
- fresh frozen plasma
- PRBC - Vitamin K
- PPI
- pantoloc - histamine H2-receptor blockers
- ranitidine - lactulose - Lactulose draws out ammonia - not for constipation
- neomycin - antibiotic that decreased bacterial flora which helps produce ammonia
Plasma - clotting factors
drug therapy for varices
- vasoconstrictors
- somatostatin, octreotide, vasopressin (+nitroglycerin) - β-adrenergic blockers
- propranolol or nadolol
describe long term management for varices
- β-adrenergic blockers (propranolol and nadolol)
- repeated sclerotherapy/band ligation
- shunt therapy
a) portosystemic shunts (non surgical)
- used to redirect portal blood flow
- decreases portal venous pressure and decompresses varices
b) portacaval shunt (surgical)
- decreases bleeding episodes
- does not prolong life; pt at risk for hepatic encephalopathy
what is portocaval shunt connecting
connects portal vein to the inferior venacava
what does splenorenal do
leaves flow somewhat intact - splenic vein is attached to left renal vein
with shunts there is a risk for
occlusion
what is the most common complication of cirrhosis
peripheral edema and ascites
describe to me peripheral edema
- peripheral edema precedes, occurs at the same time or occurs after ascites
- edema - decrease colloidal pressure-impaired synthesis of albumin and increased portocaval pressure from portal HTN
- reduced oncotic pressure from lower albumin levels
- high portocaval pressure also contributes - fluid pushed out
- retaining sodium and water - increased circulating volume
describe to me ascites
accumulation of serous fluid in the peritoneal or abdo cavity
- most common complication of cirrhosis
- portal pressure increase, proteins shift from blood to lymph space
- hypoalbuminemia - inability of liver to synthesize albumin - decrease colloidal oncotic pressure
- hyperaldosteronism - aldosterone not metabolized, increased aldosterone levels leads to increased sodium and water reabsorption in the renal tubules
ascites treatment
- sodium restriction
- high-carbohydrate, low Na+ diet (2g/day)
- fluid restriction not usually needed unless severe ascites develops - diuretics
- spironolactone + furosemide - fluid removal
a) paracentesis
- removes fluid from abdominal cavity
- temp measure
b) peritoneovenous shunt
- assess fluid and lyte balance
- may need frequent paracentesis as fluid builds
- shunt moves fluid out of the abdominal cavity continuously
abdominal paracentesis
- ostomy appliance around the site can be used if drainage continues after puncture
what is hepatic encephalopathy
- neuropsychiatric manifestation of liver damage, manifested as changes in neuro and mental function
- ammonia enters the systemic circulation w/o detoxification by the damaged liver
- ammonia levels rise
blood is shunted past liver, liver unable to convert ammonia to urea - ammonia crosses BBB
- nutrient rich blood goes from the gi to the liver from processing before it goes to the heart so toxins are not circulated through the whole body
- w/o this, ammonia levels in the body increase
- neurotoxic, lethargy, delirium-like, coma
how does hepatic encephalopathy clinically manifest
- changes in neuro and mental responsiveness
- sleep disturbance - lethargy - coma
- extrapyramidal dysfunction
- fetor hepaticus: musty, sweet breath odour
- asterixis: flapping tremors of arms and hands
acute onset - bleeding
gradual - ammonia toxicity
stiffness, bradykinesias
hepatic encephalopathy diagnosis
west haven criteria gold standard
hepatic encephalopathy collaborative care + goal
goal: decrease ammonia formation
- antibiotics
- reduce bacterial flora results decreased ammonia
- neomycin, metronidazole, vancomycin, rifaximin - lactulose
- traps ammonia in gut and then expels from the colon - cathartics/enemas
- decreased bacterial action - treatment of precipitating cause
- GI bleeding
- constipation
- lyte disorders
- acid-base imbalances
- infections
- maintain safe environment
hepatorenal syndrome signs
serious complication of cirrhosis
1. functional renal failure w
- azotemia
- oliguria
- intractable ascites
- no kidney structural abnormality
decreased MAP
hepatorenal syndrome cause
- portal HTN and liver decompensation lead to splanchnic and systemic vasodilation and decreased arterial blood volume
- renal vasoconstriction occurs, leading to kidney failure
hepatorenal syndrome management
- treatment of liver disease
- liver transplant
azotemia
excess nitrogen/waste in blood
intractable ascites
treatment resistant, reoccuring
spontaneous bacterial peritonitis
- an infection of preexisting ascitic fluid w/o evidence for an intra-abdominal secondary source
- almost always seen in the setting of end-stage liver disease
s/s of spontaneous bacterial peritonitis
fever, abdo pain, abdo tenderness and altered mental status
management of spontaneous bacterial peritonitis
- antibiotics
- broad-spectrum therapy - cefotaxime - antibiotics prophylaxis for pts at high risk for developing SBP
what is hepatocellular carcinoma
a primary tumor of the liver that usually develops in the setting of chronic liver disease
80-90% of ppl w this carcinoma also have cirrhosis
asympt until tumor is very large - usually detected very late
hard to diagnose visually w liver scarring and nodules
hepatocellular carcinoma diagnosis
- imaging (CT, MRI, U/S)
- serum tumor markers
- liver biopsy
hepatocellular carcinoma management
- liver resection
- liver transplant
- molecularly targeted agents
- chemotherapy
cirrhosis collaborative care
- rest
- can reduce metabolic demands on the liver
care of complications
- nutritional therapy
a) diet w/o complicatinos
- high in calories (3000 kcal/day)
- high carbs
- moderate to low fat
- protein restriction rarely justified
- protein supplements if protein-calorie malnutrition
- low sodium w ascites and edema - enteral feeds or TPN if necessary
risk for anorexia and n/v - inadequate nutrition
ongoing assessment and management of cirrhosis
- accurate I/O
- daily wts
- abdo girth
- lab values
- paracentesis - monitor dressing site
- observe for bleeding
- resp status - coughing and deep breathing exercises
- neurological assessment q2h
- positioning
- symptom relief
- prevention of constipation
- liver transplant
- pt edu
- age related considerations
