Liver Stuff Flashcards
THE Largest solid organ in the body is __________
The liver
THE LIVER
Weighs about ____-___ kg in adults
Only organ capable of ______ after damage or partial hepatectomy
1.o – 1.5
complete regeneration
THE LIVER
Performs numerous complex functions including:
•____genesis, _____lysis, _____genesis and ___genesis
•Manufacture of _____ proteins
•______production
Detoxification, _____ metabolism, ____ genesis
Glyco; glycogeno
gluconeo; Leto
plasma
Bile; lipid; urea
Structure of the Liver
The liver is made up of liver lobules (the ________ of the liver).
Each lobule is constructed around a _____ that empties into the _____________ which then drain into the _______
functional units
central vein
right and left hepatic veins
vena cava.
Structure of the Liver
The lobule is composed of _______ that radiate from the central vein.
Each cellular _____ is _____ cells thick and between the two cells are (small or large?) _________ that empty into _______
cellular plates
plate; two
Small; bile canaliculi
terminal ducts.
Structure of the Liver
Blood enters the liver from two sources, the _________ and ____________
hepatic portal vein and the hepatic artery.
Structure of the Liver
____% of perfusing blood is from the hepatic portal vein, ____% is from the hepatic artery
60
40
Liver structure
At each corner of the ____gonal liver lobule is a group of _____ structures:
List them !… and it’s all called ??
hexa
three
a branch of the hepatic portal vein, a branch of the hepatic artery, and a bile duct
portal triad
Liver structure
As the two blood vessels leave the portal triad, they empty into the ______ where the blood from the two sources mix. It percolates through the that, toward the ____________ where the _________ is located.
It passes through a series of veins that collect from many lobules to enter the _________ and _____ which empty into the inferior vena cava.
sinusoids
center of the lobule
central vein
right and left hepatic veins
Liver structure
The venous sinusoids are lined with _____ different cell types:
List them
two
endothelial cells
Kupffer cells
Liver structure
The venous sinusoids are lined with two different cell types:
endothelial cells - have (small or large?) pores, allows H2O and plasma proteins to pass freely.
Kupffer cells - are ______ cells capable of ___________ and other foreign matter in the blood.
Large
reticuloendothelial
phagocytizing bacteria
Formation of bilirubin from Heme
RBCs have a life span of ______
Heme is degraded in the ____ system especially ______ and ____
_____% is from RBCs and ____% from turnover of immature RBCs and cytochromes
120 days
RE
Liver and spleen
85
15
Bilirubin metabolism and jaundice
Formation of bilirubin from Heme
Heme→ _______ ( ______ )→ ______(_____)
Enzyme:_________
biliverdin; green
Bilirubin ; red/orange
Heme oxygenase
Bilirubin metabolism and jaundice
Formation of bilirubin from Heme
Bilirubin is bound to ____= (conjugate or unconjugated?) bilirubin or (direct or indirect?) bilirubin.
albumin
unconjugated
indirect
Bilirubin metabolism in the liver
______ of bilirubin by ———-
______ of bilirubin
———- of bilirubin into _____
Uptake; hepatocytes
Conjugation
Excretion; bile
Bilirubin metabolism in the liver
Uptake of bilirubin by hepatocytes
Bilirubin ________ from its carrier _______ and enters hepatocytes
dissociates
albumin
Bilirubin metabolism in the liver
Conjugation of bilirubin
In hepatocytes, bilirubin is conjugated with __________ by the enzyme _________
two molecules of glucuronic acid
glucoronyl transferase
Bilirubin metabolism in the liver
Excretion of bilirubin into bile
Conjugated bilirubin (bilirubin _________) is transpoted into ______ and then into _____.
diglucoronide
bile canaliculi
bile
Excretion of bilirubin into bile is not energy dependent
T/F
F
Process is energy dependent and is impaired in liver disease.
Bilirubin metabolism in the intestine
Conjugated bilirubin is excreted through the _______ into the _____.( Ampulla of ____).
Gut ______ break it down to _______. Which is _______ by the _______ circulation as it is water (soluble or insoluble ?) into the circulation and is excreted by the kidneys as _____ a ____ pigment in urine.
The rest is converted to ________ the ____ coloured pigment and is excreted in faeces.
common bile duct; duodenum; Vater
bacteria; urobilinogen
reabsorbed; enterohepatic
soluble; urobilin; yellow
stercobilinogen; brown
Jaundice is a clinical term .
T/F
T
Jaundice
It is the ________ discoloration of skin, nail beds, sclera and mucous membranes as a result of ———secondary to increased bilirubin levels in blood. ( ___________ )
yellow
deposition of bilirubin
hyperbilirubinaemia
Types of Jaundice
_______ jaundice
_________ jaundice
_________ jaundice
Haemolytic
Obstructive
Hepatocellular
Haemolytic jaundice
Caused by _____ of _______ in haemolytic anaemias like sickle cell anaemia
____ is produced at a rate faster than the rate of _________ by the ______
massive lysis; RBC
Bilirubin
conjugation by the liver.
Haemolytic jaundice
____eased blood unconjugated (indirect) bilirubin
Urobilinogen is ______ in urine
Incr
increased
Haemolytic jaundice
Presence of bilirubin in urine
T/F
F
No bilirubin in urine as it is bound to albumin.
Haemolytic jaundice
colour of urine is _______.
_______ stools due to increased ———, produced from increased _____.
normal
Dark coloured
stercobilinogen
urobilinogen
Obstructive Jaundice: In bile obstruction;
__________ is prevented from passing into the intestine.
Conjugated bilirubin
Obstructive Jaundice
_________ is regurgitated into the blood increasing ________ in blood.
Excessive ________ is filtered in ____ and excreted in urine giving the ___________ colour of urine.
Conjugated bilirubin
conjugated bilirubin
conjugated bilirubin; urine
yellowish brown
Obstructive Jaundice
In Blood.
Increased _________.
Elevation of ____________.
____ is normal or mildly elevated.
conjugated bilirubin
GGT and ALP
ALT
Obstructive Jaundice
In Urine.
______ appears in the urine giving _________ urine.
_______ is reduced in urine.
Bilirubin
yellowish brown
Urobilinogen
In obstructive jaundice , stool color is unaffected
T/F
With reason
Stool is pale as a result of low stercobilinogen.
Hepatocellular jaundice
FIRST.
Caused by _____ as a result of _____.
Damage to ______ causes low ______ efficiency leading to increased ___________ in _______
liver damage
hepatitis; hepatocytes
conjugation
unconjugated bilirubin in blood.
Hepatocellular jaundice
SECOND!
Conjugated bilirubin is __________. So it enters the circulation increasing conjugated bilirubin in blood.
not efficiently secreted into bile
Hepatocellular jaundice
IN Blood
Increased ________________.
______________ are markedly elevated.
BOTH conjugated and unconjugated bilirubin
ALT and AST
Hepatocellular jaundice
IN Urine.
________ is present in urine.
Urine colour is ________.
Stool is _______ . (___________)
Bilirubin
yellowish brown
Pale; low stercobilin
JAUNDICE IN NEWBORNS
In newborns especially ______ ones,
Bilirubin accumulates as liver enzyme _____________ is low at birth.
The enzyme reaches adult levels in about ________.
premature; bilirubin glucoronyl transferase
4 weeks
JAUNDICE IN NEWBORNS
Treatment.
Exposure of the newborn’s ______ to _______ which ________________________
These isomers can be _____ into ____ without __________
skin
blue fluorescent light
converts bilirubin to more polar and hence water soluble isomers.
excreted; bile
conjugation to glucuronic acid.
JAUNDICE IN NEWBORNS
Accordingly,_______ is increased in blood.
Elevated bilirubin in excess of the _______ capacity of _______, can diffuse into the ———— and cause toxic ________( ________)
unconjugated bilirubin
binding ; albumin
basal ganglia; encephalopathy
kernicterus
Congenital Hyperbilirubinaemia
Mention 4
CRIGLER- NAJJAR SYNDROME
GILBERTS SYNDROME
Dubin-Johnson syndrome
ROTOR SYNDROME
Congenital Hyperbilirubinaemia
CRIGLER- NAJJAR SYNDROME
Low _____ of _________________
It is a (common or rare?) inherited disease.
There is severe _______ in neonates – ____________.
It is complicated by ______ and early death.
activity
glucoronyl transferase
Rare
hyperbilirubinaemia
unconjugated hyperbilirubinaemia
kernicterus
Congenital Hyperbilirubinaemia
GILBERTS SYNDROME
_______ production or expression of ______.
(Common or Rare?) autosomal (autosomal or dominant?) trait.
More common in (men or women?) .
Usually (symptomatic or asymptomatic ?) hyperbilirubinaemia.
Decreased
glucoronyl transferase
Rare; dominant ; men
asymptomatic
Congenital Hyperbilirubinaemia
ROTOR SYNDROME.
Rare __________
(benign or malignant?), autosomal (dominant or recessive?) disorder characterised by ________ jaundice due to chronic elevation of predominantly ______.
mixed hyperbilirubinaemia
benign; recessive
non haemolytic ; conjugated bilirubin
Congenital Hyperbilirubinaemia
Dubin-Johnson syndrome.
Defect in ________________________________.
__________hyperbilirubinaemia.
transfer of conjugated bilirubin into the biliary canaliculi
Conjugated
In Gilbert’s syndrome, Liver function tests are not normal.
T/F
F
Liver function tests are normal.
Congenital Hyperbilirubinaemia
ROTOR SYNDROME.
Caused by impaired _______________________ that leaks into plasma causing hyper bilirubinaemia.
hepatocellular storage of conjugated bilirubin
Difference between ROTOR SYNDROME.
And Dublin-Johnson syndrome
Almost like DJ but liver has black pigmentation in Dubin Johnson that Rotor does not have.
Diseases of the liver
Classified according to aetiology
For clinical purposes, sub-classification defines the stage of the disease process (______,______,_______etc.) and the pathological state of the liver (assessed ________, ______, or _________) is also included.
acute, subacute, chronic
clinically, histologically or radiologically
Aetiology of liver disease: Viral
Hepatitis viruses ______
_________ virus
_______virus
A to E
Epstein-Barr
Cytomegalo
Aetiology of liver disease: Metabolic
______________
_______ disease
_________ hyperbilirubinemias
Hemochromatosis
Wilson
Hereditary
Aetiology of liver disease: Autoimmune
________ hepatitis
_______________
Autoimmune
Primary biliary cirrhosis
Aetiology of liver disease: Neoplastic
________
___________
Primary
Secondary
The liver has only a limited number of responses to various pathological insults, these include:
__________ and ______
Acute _______ and its sequelae ____
_____
______failure (related)
Cholestasis and jaundice
hepatitis; Chronic liver disease
Ascites
Renal
Biochemistry and hematology tests
__________ tests play a valuable role in monitoring the progress of established liver disease and in assessing the response to treatment.
Liver function
Biochemistry and hematology tests
The standard LFTs include the following groups:
_______ measurements in ______ and ___
___________ activities
_________: total protein, albumin, globulins
Measures of _____: ________ time
Bilirubin; blood and urine
Plasma enzyme
Plasma proteins
clotting; prothrombin
Infectious liver disease
Most important epidemiological causes of infectious liver disease are _____,______, and _______ infections.
viral, trematode and cestode
Infectious liver disease
________ is the commonest cause of acute hepatitis.
Viral infections
Infectious liver disease
Viral infections the commonest cause of acute hepatitis.
Range of responsible viruses very broad but those of greatest importance are the —————- ____________
hepatitis viruses A, B, C, D and E.
VIRAL HEPATITIS
Distinguished from each other by ______, modes of transmission and propensity for development of ________
morphology
chronic infections.
VIRAL HEPATITIS
A and E transmitted via ________, cause (acute or chronic?) hepatitis, long- term sequelae is (common or rare?).
B, C and D viruses _______-transmitted, associated with development of (acute or chronic?) hepatitis following ________
faecal-oral route; Acute; rare
parenterally
Chronic
initial acute phase.
VIRAL HEPATITIS
WHO estimates ________ carriers of hepatitis B virus,________ chronically infected with hepatitis C virus.
350 million
300 million
Biochemical tests
Plasma biochemical changes are different for all hepatitis viral infections.
T/F
F
Plasma biochemical changes similar for all hepatitis viral infections.
Biochemical tests: viral hepatitis
During _______ phase (even before _________), plasma aminotransferases begin to rise, may reach concentrations more than _____ times reference limits.
early acute
development of symptoms
50
Biochemical tests : viral hepatitis
In contrast to alcoholic hepatitis, plasma (ALT or AST?) usually higher than (ALT or AST?).
As _____ illness subsides, ALT and AST activities return to normal, though they may continue to be slightly elevated for weeks/months in protracted cases/ _____ infections
ALT
AST
acute
chronic
Biochemical tests: viral hepatitis
Plasma bilirubin concentrations rise more (slowly or rapidly ?) compared to plasma enzymes , peak at _______ times the reference limit.
Slowly
10 – 20
Biochemical changes: viral hepatitis
ALP and GGT activities are not elevated
F
ALP and GGT activities only mildly elevated.
Biochemical changes: viral hepatitis
Mild to moderate ________ is a frequent finding, various _______ may become detectable.
hyperglobulinemia
autoantibodies
Viral hepatitis
Sequence of events following infection varies widely, depends on ________, _______ and _______ infection is acquired, ________ and ________ to it.
which virus is involved
how and at what age
viral load and the host’s response
Viral hepatitis
In all stages, after a period of incubation (___-____ depending on the virus), ____ phase sets in, begins with general malaise, nausea, loss of apetite, fatigue, abdominal pain/discomfort, _____-like illness, followed by appearance of ____ urine, _____ faeces and the development of _____.
2 – 26 weeks
acute; influenza
dark; pale
jaundice
Viral hepatitis
Acute phase oftentimes is entirely asymptomatic or can be severe, proceding to ________ and coma, with high mortality.
Acute phase usually gradually resolves over period of _______ to _______
acute liver failure
several weeks to months.
Viral hepatitis
Mechanisms of liver damage in acute/chronic hepatitis virus not fully understood, may be due to ______ against virus-infected cells, though in ________ infections, virus-induced _______ may also play a role.
host reactions
A and B
autoimmune reactions
Hepatitis B
Transmission occurs mainly during ____, injection of blood products, though screening in most countries for HBV, development of vaccination programs has led to reduction in infections acquired this way, while monitoring of HBV-positive mothers and therapeutic intervention has led to reduction in
blood transfusion
Hepatitis B
Elsewhere, vertical transmission maintains high level of infection. Most neonates that acquire the infection become (acutely or chronically?) infected, very rarely clear virus in their lifetime.
chronically
Hepatitis B
Others will have florida liver damage that progresses to cirrhosis. About ___% of patients with cirrhosis due to HBV develop hepatocellular carcinoma each year
5
Hepatitis A
RNA virus. Transmission via _____, mainly through personal contact (especially in _______), drinking of contaminated water, consumption of _____ from sewage-contaminated waters. Clinical course is (benign or malignant?) , chronic infections seem not to occur, prognosis excellent.
faecal-oral route
children
shellfish
Benign
Hepatitis C
Transmitted ———-, though in about ___% no history of parenteral exposure obtained. Route of transmission unknown.
Acute and chronic HCV clinically (mild or severe?), usually silent.
Plasma aminotransferases are _______________. Other biochemical parameters usually normal or slightly abnormal. Mild to moderate hypergammaglobulinemia frequent finding.
parenterally
50
Mild
only moderately elevated
Hepatitis D
HDV wholly dependent on ______, acquired by same routes either as __________ or _______.
Infection can be acute or chronic.
Co-infection can lead to _________ hepatitis, first episode due to ____, second to _____.
HBV
co-infection or super-infection
biphasic acute ; HBV; HDV
Hepatitis E
_____-borne virus, infections acquired mainly through ________. Clinically similar to ______ but tends to be (more or less?) severe, greater propensity for development of _______, particularly in women infected in the ____ trimester.
Biochemical liver test results typical of acute viral hepatitis. Rapid elevation of plasma aminotransferases before or during appearance of jaundice.
Water; drinking feces- contaminated water
HAV; more ; acute liver failure
3rd
Hepatitis D
Super- infection often leads to (acute or chronic?) HDV infection which is associated with (more or less?) severe liver disease and a (more or less?) rapid progression to cirrhosis.
Occasionally HDV infections are very severe, lead to _____ failure which carries a high mortality.
Chronic
More
More
acute liver
Acute hepatitis and its sequelae
Acute inflammation of the liver associated with hepatocellular damage is most often caused by ______ or ______ including _____ and ______
Symptoms depend on the ______ of the process and the individual’s ____ to the damaging agent.
viruses or toxins
drugs and alcohol.
severity; response
Acute hepatitis and its sequelae
There are three main possible outcomes:
__________
Progression to _________ of varying severity
______________
Complete resolution
chronic liver disease
Acute liver failure (ALF)
Acute hepatitis and its sequelae
The distinction between acute and chronic liver disease is a ______ one. The usual yardstick is persistence of signs and symptoms, clinical or biochemical for more than ________.
temporal
six months
Chronic liver disease
The initial onset is (easy or difficult?) to define.
For example ________ and ________ have no recognizable acute phases and develop (slowly or rapidly ?) with few symptoms over many months or years.
Difficult
primary biliary cirrhosis and hemochromatosis
Slow
Chronic liver disease
In chronic hepatitis ___, initial viral infection is clinically _____ and disease may not become apparent for ____ to _____
C
silent
20 or 30 years.
Chronic liver disease
Chronic hepatitis was previously classified on histological criteria as
•Chronic active hepatitis (CAH), which has a high propensity to progress to
_______ and/or _______ and
•Chronic persistent hepatitis, a more (benign or malignant ?) form which could occasionally progress to ____.
cirrhosis; liver failure
benign
CAH
Chronic liver disease
Chronic hepatitis was previously classified on histological criteria as
__________
And
____________
This classification is not in use anymore as it seems they __________________________
Chronic active hepatitis (CAH)
Chronic persistent hepatitis
represent extremes of a continuous spectrum of changes in the liver.
Chronic liver disease
Chronic active hepatitis has been supplanted by the term _____ hepatitis, ______
interface
cirrhosis
Following a single short-lived insult the liver can recover completely with normal architecture.
T/F
T
Cirrhosis
When the cause of the damage _______ e.g in ______ viral infection, the capacity of the ________ process to keep pace with the liver cell death may be exceeded.
persists; chronic; regenerative
In Cirrhosis
A number of events ensue:
•__________ supporting liver cell plates collapses and condenses to form ____________
•____ cells, _____ cells and _____ which promote _____ become activated through the influence of various cytokines.
•As more fibrous tissue forms, architecture of the liver become disrupted and this disruption affects the ________, leads to further cell death. This is the _____________ result of any chronic process which involves recurrent waves of cell death and attempts by the liver to regenerate.
Reticulin framework; fibrous scar tissue.
Ito; perisinusoidals; lipocytes; fibrogenesis
blood vessels; irreversible end
Compensated cirrhosis
Even when cirrhosis has developed there may be sufficient tissue for the liver to continue performing most of its normal functions, patients may have no symptoms.
Cirrhosis in these cases said to be (poorly or well ?) compensated.
In other cases there may be rapid deterioration (________) with development of _______ and _______
Well
decompensation
complications and liver failure.
Portal hypertension
Increased blood pressure in the _____ due to increased resistance to the flow of blood through the _____ as a result of extensive _______ deposition in the liver with patients with _______.
portal vein ; liver
fibrous tissue ; cirrhosis
Portal hypertension
Consequence of this increased portal pressure is blood is diverted into lower pressure _____ especially the veins around the upper end of the stomach and lower end of esophagus, also around the rectum and anterior abdominal wall (_____________).
systemic circulation
portal-systemic shunting
In Portal hypertension
Spleen becomes enlarged due to back pressure created in the ________ which drains into the _____
splenic vein
portal vein
Clinical importance of portal hypertension
•Hemorrhage from _____ or _____
•Natural ______ and _____ functions of the liver are bypassed, this increases risk of developing hepatic ________
esophageal or gastric varices
filtering and detoxifying
encephalopathy
Clinical importance of portal hypertension
Hypersplenism is associated with ___________ in the spleen and the resulting ____ and _______ in the systemic circulation decreases the patient’s resistance to infections.
sequestration of WBCs
neutropenia and thrombocytopenia
Ascites
Excessive accumulation of _____ in the _________.
Usually a Complication of ________
ECF
peritoneal cavity
advanced cirrhosis
Ascites Can also develop as a result of other non-hepatic conditions
T/F
With example
T
Mechanism due to Na retention as a result of secondary hyperaldosteronism compounded by hypoalbuminemia, fluid is localized in the peritoneal cavity because of portal hypertension.
Urine in such patients virtually Na free
Ascites
Treatment of ascites includes bed rest, _____,____, and ______
However careful monitoring is required to ensure serious complications (_______ of the ascites) do not occur.
salt restriction, diuretics and paracentesis.
bacterial infection
Renal failure
Renal failure is an ever present risk in patients with ________, usually precipitates _______.
Onset indicated by rising plasma concentrations of ______ and _____ and a decreased _______.
advanced cirrhosis
encephalopathy
creatinine and urea
urine output
Renal failure
Hyper_______ is a particularly lethal complication
The _______ syndrome is an idiopathic form of renal failure associated with advanced liver disease, ascites and encephalopathy.
kalemia
hepatorenal
Renal failure
Characteristic feature of hepatorenal syndrome is that kidneys are histologically ______ but there is disturbance of ______.
Precipitating event is _______ leading to decreased ________ and reduced ________
normal
function
renal vasoconstriction
renal blood flow
glomerular filtration rate
In hepatorenal syndrome
there is (rising or dropping ?) plasma creatinine and urea concentrations.
Most dramatic feature which distinguishes it from acute tubular nephrosis is dramatic increase in _________
Rising
sodium retention
Tests of chronic liver disease
Low _____, impaired ______ and raised _____ are features associated with poor prognosis in patients with chronic liver disease.
albumin; clotting; bilirubin
Tests of chronic liver disease
Scoring systems also exist which can help in selecting patients for liver transplantation e.g _____________________ includes:
Extent of ______
Grade of ________
Plasma _______ and plasma ______
Child Pugh score for cirrhosis
ascites; encephalopathy
albumin; bilirubin
Tests of hepatic fibrosis
Most important test of fibrosis is _______ but ___________ exist, the most important being the ______ terminal ________________________
histology
biochemical markers
amino-terminal pro-collagen type III peptide (PIIINP)
PIIINP is used in the monitoring of patients with _______ therapy where ______ can occur.
chronic methotrexate
Other markers of hepatic fibrosis include
_____,______,______ and ________
prolyl hydroxylase, laminin, fibronectin and type 7S collagen.
With the exception of _____ which measures the ______, and _____ which measures ______ and ______, most LFTs are indicators of liver _____ rather than ______.
albumin; synthetic function
bilirubin
conjugation and excretion
damage; function
Tests of hepatocellular activity (quantitative liver function tests)
Quantitative assessment of the functional hepatic mass would allow the hepatologist to judge when patients with ________ disease are __________ and plan therapeutic interventions such as ____________ accordingly.
chronic liver
nearing end-stage hepatic failure
liver transplantation
Tests of hepatocellular activity (quantitative liver function tests)
Various tests have been proposed based on the ability of the liver to ____________________
clear exogenous compounds from the body.
Quantitative tests for hepatocellular activity include:
___________ capacity
________ breath test
____________ clearance
______________ formation test
Galactose elimination
Aminopyrine
Indocyanine green
Monoethylglycineexylidide
Reference intervals
AST- ___-___
ALT- ___-____
ALP- ___-____
5-30
6-37
30-90
