2. Should be able to define cirrhosis
Should be able to classify cirrhosis
Should be able to work up CLD
be able to mention complications of CLD
4. liver -- receives a dual blood supply; ~20% of
the blood flow is oxygen-rich blood from the
hepatic artery, and 80% is nutrient-rich blood
from the portal vein arising from the
stomach, intestines,pancreas,andspleen
(almost from entire GI- through Superior /
Inferior mesentry)
5.
6.
7.
8.
9. hepatocytes, constitute 2/3
stellat(13% )
Kupffer cells
endothelial cells and blood vessels, bile
ductular cells, and supporting structures
10. Liver cells :
1-- hepatocytes, constitute 2/3.has distinct
polarity; Disse space & microvilli with passive
and active uptake of nutrients, proteins, and
other molecules.
Plays vital roles in maintaining homeostasis and
health; synthesis serum proteins
(albumin, carrier proteins, coagulation
factors, many hormonal and growth factors), the
production of bile and its carriers (bile
acids, cholesterol, lecithin, phospholipids), the
regulation of nutrients
(glucose, glycogen, lipids, cholesterol, amino
acids), and metabolism and conjugation of
lipophilic compounds
(bilirubin, anions, cations, drugs) for excretion in
the bile or urine.
11. 2-- Kupffer cells (reticuloendothelial
system), lie within the sinusoidal vascular
space and represent the largest group of
fixed macrophages in the body.
3---stellate (Ito,fat-storing ) 13%-
(retinoid;vitA metabolite storage), not
prominent unless activated, when they
produce collagen and matrix in large.
4-- endothelial cells and blood vessels, bile
ductular cells, and supporting structures.
12.
13.
14.
15. Def : cirrhosis is irreversible hepatic damage
; histologically characterized by loss of
hepatic architecture with fibrosis & nodular
regeneration.
26. Primary biliary cirrhosis(PBS) :
progressive granulomatous inflamm
interlobular bile ducts damage cirrhosis
Cause : unknown ? Autoimmune ,
Affect : 90% middle age women
27. Primary sclerosing cholangitis(PSC)
Progressive obliterative inflamm of intra &
extra hepatic bile ducts fibrosis cirrhosis
Cause : unknown ? Autoimmune
>70% asssociate with Ulcerative colitis
28. Hemochromatosis:
Autosom disorder of Fe metabol X-ed by high
Fe absorption deposition in multiple organs
(LIVER, PANCREASE, HEART
,PITIUTARY, JOINT)
Affect : middle age men, loss through mensus
protect women.
29. Wilson’s Disease :
Inherited disorder X-ed by failure to
excrete copper(failure to prepare
Cu,transportingATPase , for biliary excretion)
accummulation of toxicCu in LIVER&BRAIN
Kayser-Fleischer ring : pathognomonic(usually)
brownish pigment ring at the periphery of
cornea
43. Spiderangiomata/ spider
telangiectasias-- are vascular lesions consisting of
a central arteriole surrounded by many smaller vessels on
trunk, face, and upper limbs.
pathogenesis is incompletely understood, believed to
result from alterations in sex hormone metabolism; in men
increase in the estradiol/free testosterone ratio
not specific for cirrhosis can be seen during pregnancy
, severe malnutrition.
As a general rule, the number and size of spider angiomata
correlate with the severity of liver disease . Patients with
numerous and large spider angiomata may be at increased
risk for variceal hemorrhage.
44.
45. Palmar erythema — exaggeration of the normal
speckled mottling of the palm, believed to be
caused by altered sex hormone metabolism . on
the thenar and hypothenar eminences while
sparing the central portions of the palm. not
specific for liver disease ,can be seen in
pregnancy rheumatoid
arthritis, hyperthyroidism, and hematological
malignancies.
46. Muehrcke's nails --paired horizontal white
bands separated by normal color. caused by
hypoalbuminemia .not specific for
cirrhosis, also be seen in other conditions
with hypoalbuminemia.
Clubbing — angle b/n nail plate and proximal
nail fold >180degree. severe form[grade4] is
drum stick. more common in biliary causes of
cirrhosis (particularly primary biliary
cirrhosis) ,but not specific for liver disease.
47.
48. Dupuytren'scontracture — thickening and
shortening of the palmar fascia with flexion
deformity ,fibroblastic proliferation and
disorderly collagen deposition with fascial
thickening. The pathogenesis is unknown but
may be related to free radical formation
generated by the oxidative metabolism of
hypoxanthine
49.
50. Gynecomastia — benign proliferation of the glandular
tissue of the male breast and clinically by the presence of
a rubbery or firm mass extending concentrically from the
nipple(s). Fat deposition without glandular proliferation is
termed pseudogynecomastia ( obese men). These two
entities can be distinguished by having the patient lie on
his back with his hands behind his head. The examiner
then places his or her thumb and forefinger on each side of
the breast, and slowly brings them together.
caused by increased production of androstenedione from
the adrenals, enhanced aromatization of androstenedione
to estrone, and increased conversion of estrone to
estradiol. Men may also develop other features reflecting
feminization such as loss of chest or axillary hair and
inversion of the normal male pubic hair pattern.
Gynecomastia can be seen in a variety of conditions other
than cirrhosis.
51.
52. Testicular atrophy — Hypogonadism is manifested
by impotence, infertility, loss of sexual
drive, and testicular atrophy. It is a feature seen
predominantly in patients with alcoholic
cirrhosis and hemochromatosis. More than one
mechanism appears to be involved. In some
cases, primary gonadal injury appears to be
more prominent, as suggested by increased
serum FSH and LH concentrations, while in
others suppression of hypothalamic or pituitary
function appears to have a primary role, as
suggested by serum LH concentrations that are
not elevated. The toxic effects of alcohol or iron
may also contribute to its development.
53. Hepatomegaly — cirrhotic liver may be enlarged, normal sized, or
small. While the presence of a palpable liver may indicate liver
disease, a non-palpable liver does not exclude it. When
palpable, the cirrhotic liver has a firm and nodular consistency.
Splenomegaly — caused by congestion as the result of portal
HTN .
other several ddx are possible.
. Ascites — accumulation of fluid in the peritoneal cavity. The
accuracy of physical findings is variable depending in part upon
the amount of fluid present, the technique used to examine the
patient, and the clinical setting (eg, detection may be more
difficult in patients who are obese). In one study, the absence of
flank dullness was the most accurate predictor against the
presence of ascites; the probability of ascites being present was
less than 10 percent in such patients . However, approximately
1500 mL of fluid had to be present for flank dullness to be
detected. Shifting dullness is more specific.
54. Caput medusae — The veins of the lower
abdominal wall normally drain inferiorly into the
iliofemoral system while the veins of the upper
abdominal wall drain superiorly into the veins of
the thoracic wall and axilla. When portal
hypertension occurs as the result of
cirrhosis, the umbilical vein, normally
obliterated in early life, may open. Blood from
the portal venous system may be shunted
through the periumbilical veins into the
umbilical vein and ultimately to the abdominal
wall veins, causing them to become prominent.
This appearance has been said to resemble the
head (caput) of the mythical Gorgon Medusa.
55. Dilated abdominal veins can also be seen in the IVCS
and SVCS (if obstruction includes the azygous system)
. In these conditions, collateral veins tend to be more
prominent in the lateral aspect of the abdominal
wall. One maneuver that has been proposed to
distinguish vena caval obstruction from portal
hypertension is to pass the finger along dilated veins
located below the umbilicus to strip them of blood
and determine the direction of blood flow during
refilling. In portal-systemic collateral veins, the
blood flow should be directed inferiorly away from
the umbilicus in contrast to vena caval collateral vein
flow in which the flow should be cephalad.
However, the actual ability of this maneuver to
discriminate between the two is poor since in both
conditions the dilated veins may lack valves and thus
have bidirectional blood flow .
56. Fetor hepaticus — A sweet, pungent smell to the
breath of a cirrhotic patient may occasionally be
encountered. It is caused by increased concentrations
of dimethylsulphide, the presence of which suggests
underlying severe portal-systemic shunting .
Jaundice — yellow coloring of the skin and mucus
membranes that results from increased serum
bilirubin. It is usually not detectable until Tbil > 3
mg/dL. The hyperbilirubinemia may also cause the
urine to appear dark or "coca-cola" colored.
Yellow discoloration to the skin can also be caused
by excessive consumption of carotene ( carrots). But
can be distinguished from jaundice by the absence of
yellow discoloration in the sclera in the former.
57. Asterixis— bilateral but asynchronous
flapping motions of outstretched, dorsiflexed
hands ,is seen in patients with hepatic
encephalopathy, ?may also be seen in
patients with uremia and severe heart
failure.
58. In most instances can be made accurately by
a careful history, physical examination, and
application of a few laboratory tests.
In some circumstances, radiologic
examinations are helpful
or, indeed, diagnostic.
Liver biopsy is considered the "gold standard"
in evaluation of liver disease but is now
needed less for diagnosis than for grading
and staging disease.
59. Lab
LFT can be normal, >3-5x UNL or
1, AST(SGOT)
ALT(SGPT) <40Iu/ml
AST/ALT <0.8 , >2 in alcoholic LD
2,Alk ph - usually elevated but <3X the
upper normal limit. Higher levels in psc &
pbc
60. 3,Bilirubin (N T <1mg/dl;17microg/dl ,D<0.3
N in compensated, in advanced cirrhosis
4,Albumin- as the synthetic function of the liver
declines with worsening cirrhosis;helps to grade the severit
of cirrhosis.But not specific for liver disease,can be seen
CHF, NS, protein losing enteropathy, or malnutrition.
61. 5, Prothrombin time
liver synthesize 11 blood coagulation proteins; Factor I
(fibrinogen), II (prothrombin), V , VII , IX , X , XII and XIII
can be measured individually or indirectly by more general
measures of clotting ability such as the PT.
CoagFactors ( liver capacity to synthesize) = PT prolong
Globulins- in cirrhosis(infection), IgG in AIH ,IgM in
PBC
62. Serum Na+ — Hyponatremia is common
in cirrhosis with ascites &severe in ESLD ;
inability to excrete free water; high levels of
ADHsecretion.
Hematologic abnormalities
Anemia — multifactorial ; acute and
chronic GI blood loss, folate
deficiency, direct toxicity due to
alcohol, hypersplenism,BMsuppression,ACD
(inflammation), & hemolysis may all
contribute.
63. Thrombocytopenia
- portal HTN congestive splenomegaly
sequestration of up to 90 % of circulating
platelet mass.
- thrombopoietin
Leukopenia and neutropenia —
due to hypersplenism
65. Alcoholic liver disease- History of alcohol abuse , AST/ALT >2
Chronic hepatitis C- ELISA assay for anti-HCV ,PCR for HCV-RNA
PBC- Antimitochondrial antibodies
PSC holangitis - Strong association with IBD, cholangi
AIH -Hypergammaglobulinemia ,AntinuclearASMA,ALKA
Chronic hepatitis B - HBsAg and HBeAg and, HBV DNA
Hereditary hemochromatosis- Family history of cirrhosis
,Serum ferritin & iron,transferritin satur>80% , TIBC ,biopsy-
hepatic Fe index,genetic tes
Wilson's disease - Family or personal history of cirrhosis at a
young age ,serum ceruloplasmim,biopsy -Co
AATdeficiency- Family or personal history of cirrhosis at a young
age,serumAAT,phenotyping
NASH - History of diabetes mellitus or metabolic
syndrome, hepatic imaging , biopsy
67. grade A- total score of 5-6 ;well-compensated
disease ;100-85% of 1-2yr survival
grade
B- total score7-9 ;significant functional
compromise ;80-60%of 1-2yr survival
gradeC- total score 10-15 decompensated disease
;45-35% 0f 1-2yr survival.
68. goals :
- Slowing or reversing the progression of liver
disease
- Preventing superimposed insults to the liver
-Preventing and treating the complications
-Determining the appropriateness and optimal
timing for liver transplantation
69. Abstinence from alcohol .
Interferon therapy to HCVslows the
progression,fibrosis &risk of HCC.
Rx of chronic HB with lamivudinsignificant
improvement in liver function and histology
& risk of HCC
Rx autoimmune hepatitis with
immunosuppressive agents10yr survi 90 %
70. Phlebotomy , Chelation ,Dietary restriction
of iron – for HH
Chelating –for wilson D
71. AVOID
substance abuse; alcohol,
acetaminophen ,NSAIDs
hepatotoxic drugs & herbal remedies.
Give Vaccination — against HAV & HBV can
prevent a superimposed insult to a liver
Pneumococcal vaccine
yearly influenza vaccination
82. VARICES - are collateral vessels that develop
because of PHT; 1/3of pts with cirrhosis & 1/3 of
them will develop bleeding.
LOCATION—
-distal esophagus (commonst) ; thinnest coat
and at risk to bleed, - stomach, -Rectum, -
Umbilicus,…
FACTORS risk of bleeding : --PHTN >12mmhg ,--
severity of cirrhosis (Child's class),--size of the
varix ,--location of the varix,-- endoscopic
stigmata(red wale signs& …)
85. a --- fluid and blood product replacement
b ---medical ;
1-somatostatin or Octreotide , Vasopressin= direct
splanchnic vasoconstrictor, is given at dosages of 50–100
g/h by continuous infusion.
c---surgical ;
1-Balloon tamponade (Sengstaken-Blakemore tube or
Minnesota tube)
2- endoscopic therapy ( first-line to control active-vigorous
bleeding by EVL & /or variceal injection therapy
(sclerotherapy)
3- transjugular intrahepatic portosystemic shunt (TIPS)under
angiographic guidance
86. a---repeated variceal band ligation until
varices are obliterated.
b---adjunctive Beta blockade (for recurrent
variceal band ligation ,But no need once
obliteration achieved)
c---TIPS
87. Highrisk group to develop reccurrent
variceal bleeding ?
Prognosis of variceal bleeding ?
Other causes for UGIB ?
88. Risk factors for recurrent variceal hemorrhage
Age >60 years
Severity of initial bleed
Renal failure
Severity of liver failure
Ascites
Hepatoma
Active alcoholism
Active bleeding on endoscopy
Increasing varix size
Red signs yes
coagulopathy
Portal pressures
90. def: pathologic accumulation of fluid in the peritoneal
cavity
mechanism: multifactors
1] PORTAL HYPERTENSION
is the first step toward fluid retention in cirrhosis.
>12 mmHg required.
cirrhosis without PHT do not develop ascites
ascites disappear if <12 mmHg
■Portal hypertension exerts a local hydrostatic pressure
hepatic and splanchnic production of lymph
&transudation of fluid into the peritoneal cavity.
91. 2] Na RETENTION :
splanchnic vasodilatation-Arterial underfilling
- Activation Renin-Ang-Aldos -- Na retent-
3] HYPOALBUMINEMIA :
synthetic function of cirrhotic liver
Hypoalbuminemia plasma oncotic
pressure loss of fluid from the vascular
compartment into the peritoneal cavity.
92. incidious abdominal distension ;
( high Na diet,HCC ,splanchnic vein thrombosis
Precipitate)
Abdominal pain ; SBP
Respiratory distress ( Rt pleural effussion )
Malnourish; muscle wasting and excessive
fatigue and weakness.
bulging flanks, fluid Waves ,shifting dullness
+v ,sign of pleural effussion.
94. test
1-Cell cout & diff - N >250 SBP
2-Gram stain,AFB and culture -
3-Protein -3.1 SAAG
-3.2 [total protein]
4-Cytology - for malignant cells.
5-Amylase - to exclude pancreatic ascites
95. test
1-Cell cout & diff - N >250 SBP
2-Gram stain,AFB and culture -
3-Protein- serum ascites-to-albumin gradient (SAAG) ;
[total protein] in ascites is quite low in cirrhosis; <1 g/dL
SAAG=serum alb minus ascitic albumin ( not ratio )
>1.1 g/dL indicates PHT-cirrhosis with 97%accuracy &
High-gradient (transudative
remains stable unless PHT
<1.1 g/dl indicates abscence of PHT,
Low-gradient (exudative)
but infectious(opsonization) or malignant (peritoneal carcinomatosis, tuberculous
peritonitis, pancreatitis, serositis, pyogenic peritonitis, and nephrotic syndrome)
4-Cytology - for malignant cells.
5-Amylase - to exclude pancreatic ascites
96. Bilirubin — in brown ascites. As mentioned
above, an ascitic bilirubin > of serum
suggests bowel or biliary perforation into
ascites
Glucose —
Lactate dehydrogenase
Triglycerides — milky/ Chylous ascites has TG
> 200 mg/dL
97. dietary sodium restriction
spironolactone at 100–200 mg/d- 400–600mg
furosemide 40–80 mg/d- 120–160 mg/d
repeated large-volume paracentesis(refractory
ascites)
TIPS (refractory ascites)
liver transplantation
prognosis of cirrhosis with ascites is
poor, survive 2 years <50%
104. Subtel- due to separation of visceral & parietal
peritoneum
Fever 69
Abdominal pain 59
Altered mental status 54
Abdominal tenderness 49
Diarrhea 32
Paralytic ileus 30
Hypotension 21
Hypothermia 17
105. Def : ascitic fluid infection in which there is a positive ascitic
fluid bacterial culture and an ascitic fluid PMN count ≥ 250
cells/mm3 with an evident intraabdominal surgically-
treatable source of infection .
Two varieties :
1--perforation peritonitis (eg, perforated peptic ulcer into
ascites)
2--nonperforation peritonitis (eg, perinephric absces
NB-mortality 100% if treatment consists only of antibiotics
with no surgical intervention . And 80% if a patient with
SBP receives an unnecessary exploratory laparotomy .
106. Clinical — both can be ( even frank perforation)
subtle b/c peritoneum separation by Ascites
Analysis — PMN count ≥ 250 with two or more of
[Total protein ] >1 g/dL (10 g/L)
[ Glucose ]<50 mg/dL
[ LDH >UNL for serum
Imaging studies —
plain and upright abdo minal films
water-soluble gut contrast studies( extravasation
of contrast
SBP-Rx response follow up ---
with repeat analysis after 48hrs ; PMN is lower
108. 1- third-generation cephalosporin
?2-combination of ampicillin
and gentamicin .
Third-gener + metronidazol
For secondary BP
109. third-generation cephalosporin benefits
over ampic/genta-combination:
A-- A higher rate of resolution of the infection — 85 versus 56
%
B--No /less nephrotoxicity versus 5 % with ampicillin-
gentamicin
C-- No superinfection versus 14 percent with ampicillin-
gentamicin
.
111. Def : ?potentially reversible neuropsychiatric
syndrome seconday to liver diseases
CLD,END-STAGE Or acute fulminant hepatic
failure.
112. Ammonia — cause in >90% + other neurotoxins
Produced--- colonic bacterial catabolism of nitrogenous
source; ingested protein and secreted urea.
Enters the circulation via the portal vein
Liver clears almost all by converting into glutamine &
prevent entry into the systemic circulation
In cirrhosis ,portal blood bypasses the liver via the collaterals
and the 'toxic'metabolites pass directly to the brain
( impaired liver blood ammonia )
Induced alteration of brain neurotransmitter balance -
especially at the astrocyte-neurone interface
114. High dietary protein
GI- haemorrhage
Constipation
Vomiting /Diarrhea
Infection; SBP , sepsis
Fluid and electrolyte ( k+ )disturbance due to:diuretic therapy,paracentesis
Drugs (e.g. anyCNSdepressant) Benzodiazepines,Narcotics ,Alcohol
Portosystemic shunt operations, TIPS Any
surgical procedure Progressive liver damage
Development of hepatocellular carcinoma
115. change in personality
confused
Can be quite violent and difficult to manage
Or very sleepy and difficult to arouse
Asterixis "liver flap‖
hepatic coma due Brain edema -herniation
116.
117. mainstay lactulose--, a nonabsorbable disaccharide
eliminat nitrogenous source
R x of precipitats
?Restriction of dietary protein
neomycin + metronidazole =Poorly absorbed antibiotics as
adjunctive therapies or alternative to lactulose
rifaximin.
?Zinc supplementation
Prognostic worse as stage progress
118. refers === development of acute renal failure in
advanced liver disease, severe alcoholic
hepatitis, (less often) metastatic tumor, and
acute fulminant hepatic failure from any cause.
MECHANISM :
portal hypertension -splanchnic
vasodilatation - hypotension-induced
activation of the renin-angiotensin and
sympathetic nervous system- renal perfusion
( GFR )
119. Type I HRS--- more serious type; progressive
impairment in renal function and a
significant reduction in creatinine clearance
( 50% )within in <2wks,serum Cr.2.5mg/dl
, oliguria
Type II HRS ; less severe. GFR and Cr
120. midodrine --is a systemic vasoconstrictor
alpha1–agonist--
octreotide -- inhibitor of endogenous vasodilator
, in combination
intravenous albumin
liver transplantation
prognosis is poor unless transplant can be
achieved within a short period of time
121. 90% of primary hepatic malignancy
One of the most common malignancies ,4th
leading death , affecr men commonly
1 million/yr with MR=250,000/yr
Liver cirrhosis, HBV, HCV are most important
risk factors
Most Asymtomatic or present with abdomen
pain or liver failure s/s
Px=survive 2-6 months if unRxed
122. Causes of HCC:
Viral infection: B,C,D; cirrhosis from
HBV,HCV, HH --at highest risk, while AIH,NASH
&Wilson's d lower risk.HBV even at carrier state
is high risk.
Toxins:Alcohol, aphlatoxin B1, tobaco,Thorium
oxide, Vinyl chloride monomers
Metabolic liver ds:
hemochrom,alpha1,PCT,glycogen storageI, II
Others: BCS, Liver flukes, androgeic anabolic
hormones, etc
123. S/S:nonspecific similar
Hard irregular hepatomegally with bruit and
cachexia and splenomegally
Portal vein thrombosis
Coagulopathy
Multiorgan failure
Portal HTN
124. Extrahepatic -- most common sites are
lung, intraabdominal lymph nodes, bone, and
adrenal gland; brain metastases are
extremely rare . Extrahepatic metastases are
more common in patients with intrahepatic
tumors >5 cm in diameter
127. Treatment & prevention
Quarterly U/s & AFP for CLD for early HCC DX
RX: Ethanol, chemoembolz, resection, LTx,
palliative care; RT, HormonalRx
Mass HBV vaccination and CLD Rx for
prevention
128. can be asymptomatic OR can present with
complication of cirrhosis
RUQ pain ,weight loss , early satiety, or a
palpable mass in the upper abdomen.
Obstructive jaundice r ,dyspnea (
metastases), Intraperitoneal bleeding ( tumor
rupture)
Hepato/splenomegaly with bruit
Paraneoplastic syndromes —
hypoglycemia, erythrocytosis, hypercalcemia, se
vere watery diarrhea,and cutaneous
manifestation
129. Patterns of metastatic spread —
Extrahepatic -- most common sites are
lung, intraabdominal lymph nodes, bone, and
adrenal gland; brain metastases are
extremely rare . Extrahepatic metastases are
more common in patients with intrahepatic
tumors >5 cm in diameter .
130. Alpha-fetoprotein --- glycoprotein that is
normally produced during gestation by the
fetal liver and yolk sacr can
pregnancy, with tumors of gonadal
origin, and chronic liver disease ;acute or
chronic viral hepatitis
NORMAL=10 and 20 mcg/L
>500 mcg/L in high risk group is suggest to
HCC
IMAGING
BIOPSY
132. regulationof protein and energy metabolism
catabolic, and muscle protein is
metabolized,
poor dietary intake, alterations in gut
nutrient absorption, and alterations in
protein metabolism.
Dietary supplementation is helpful
133. Coagulopathy is almost universal in cirrhosis.
synthesis of clotting factors and impaired
clearance of anticoagulants.
thrombocytopenia from hypersplenism
Vitamin K absorption – AFFECTdependent
CF ( II, VII, IX, & X )
134. anemia from --persplenism, hemolysis, iron
deficiency, and perhaps folate deficiency
from malnutrition.
Macrocytosis
Neutropenia from -hypersplenism.
135. Osteoporosis-
malabsorption of vitamin D &
calcium ingestion
136. HARRISON’S PRINCIPLES OF INT.MEDICINE 17th
EDITION
UpTODate 17.2
KUMAR CLINICAL MEDICINE 6th EDITION