Pathophysiology of GIT II
Exocrine pancreas
Liver
Biliary tract
Pancreas - anatomy
Pancreas – structure & function
Pancreas – endocrine gland (2%)
• -cells
• insulin
• - cells
• glucagon
• -cels
• somatostatin
• pancreatic
polypeptide
• amylin
Pancreas – exocrine gland (85%)
• secretion of pancreatic juice (pH up to 8.3)
• approx. 1-1.5l day
• production stimulated by acetylcholine, CCK and
secretin produced in duodenum
• production inhibited by pancreatic polypeptide and
somatostatin (ileum)
• composition
• ions and water ( secretin)
• Na, Cl, K and HCO3- (up to 150 mmol/l)
• HCO3- necessary to neutralize acid content of stomach, for
activation of pancreatic. enzymes and formation of micelle
• enzymes ( CCK)
• active - lipase, amylase, ribonuclease, deoxyribonuclease
• inactive (activated by enterokinase in duodenum) trypsinogen,
chymotrypsinogen, prokarboxypeptidase,
proelastase, phospholipase A2
• inhibitors of trypsin (1-antitrypsin)
• disorder of secretion – exocrine pancreatic
insufficiency
• most often due to chron. pancreatitis
• carcinoma of pancreas, cystic fibrosis, protein
malnutrition
Anatomic aspects important for pancreatic PP
PANCREATIC DISEASES
Acute pancreatitis
• acute destruction of pancreatic tissue
and neighbouring tissue due to
autodigestion by pancreatic
enzymes activated directly in the
gland
• forms
• mild – interstitial oedema of the gland
• severe (haemorrhagic-necrotic) - very
serious condition associated with high
mortality
• symptoms
• intensive pain
• nausea and vomiting
• meteorism
• fever
• circulatory shock
• diagnostics - laboratory
• alpha-amylase (event. pancreatic
isoenzyme)
• ≥3-times increase in blood, present in urine
too
• diff. dg. biliary inflammation or obstruction,
appendicitis, gynaecologic, renal
insufficiency, macroamylasemia, salivary
gland trauma, parotitis)
• lipase (specific)
Aetiology of acute pancreatitis
• biliary (60-80)
• blockade of common bile duct or
papilla Vateri by gallstone and
subsequent increase of intra-ductal
pressure
• alcohol (20-30)
• relaxation of sphincter of Oddi
• reflux of the intestinal juice and
bile into the pancreatic duct and
activation of enzymes
• increased viscosity of pancreatic
juice and its stagnation if the duct
• fusion of zymogenic granules with
lysosomes and activation of trypsin
• idiopathic (10)
• other causes
• abdominal trauma
• infection
• hypertriglyceridemia
• hypercalcaemia
• drugs
Pathogenesis of acute pancreatitis
• intracellular (in acinar cells) and extracellular (in ducts)
activation of trypsinogen to trypsin (by cathepsine B in
low pH) and subsequently of other proteolytic
enzymes/cascades responsible for autodigestion of
gland and systemic effects
• chymotrypsin, elastase, phospholipase and
carboxypeptidases
• elastase digests elastin in vessel walls  haemorrhage into
gland, leak of juice into circulation and damage of systemic
circulation
• lipolysis of pancreas by pancreatic lipase and phospholipase A2
• complement
• kallikrein – kinin system
• overrunning of protective mechanisms – anti-proteases
(SPINK1, 1 anti-trypsin etc.)
• local effects
• pancreas oedema, hyperaemia and autodigestion
• necrosis
• deposition of calcium – fatty necrosis
• C5 chemo-attraction and infiltrations by PMNs 
inflammation and release of cytokines
• systemic effects
• SIRS and event. sepsis (peritonitis)
• ARDS (phospholipase  lecithin  pulmonary surfactant)
• hypovolemic shock
• event. AKI
• DIC
Pathogenesis of acute pancreatitis
Natural history of pancreatic disease
Chronic pancreatitis
• chronic inflammation of pancreas leading to progressive
dysfunction and structural damage of pancreatic acini with
stenosis and dilation of ducts, fibrosis and atrophy of gland
and calcium depositions in ducts
• aetiology
• alcohol abuse (70 – 90%)
• >5 yrs. in quantity of 150 g/day and more
• BUT!! only 5-15 % of heavy drinkers have chron. pancreatitis
• evidently other factors are important
• genetic
• cationic trypsinogen gene (PRSS1) – gain of function mutation
• serine protease inhibitor Kazal type (SPINK1) – loss of function mutation
• cystic fibrosis trans-membrane conductance regulator (CFTR)
• chymotrypsiniogen
• cathepisn B
• calcium sensing receptor
• dietary
• others
• idiopathic (20 – 30%)
• hypertriglyceridemia
• hypocalcaemia
• chron. malnutrition
• tropical form
• hereditarily
• cystic fibrosis
• clinical forms
• painful
• pain is typically localised in epigastrium and propagates to back
• nausea and vomiting van be present too
• silent (approx. 5 %)
Pathogenesis of chron. pancreatitis
• alcohol metabolism
produces toxins causing
lipid peroxidation,
inflammation and increase
of cytoplasmic Ca
• liver  acetaldehyde
• pancreas  fatty acid
ethanol esters (FAEEs)
• alcohol increases viscosity
of pancreatic juice 
precipitation of proteins
and obstruction od ducts
• inflammatory signals
stimulate pancreatic
stellate cells (PSC) to
produce connective tissue
 fibrosis of the gland
Consequences of chron. pancreatitis
• Malabsorption of macro- and micronutrients
• absence of lipase
• maldigestion and malabsorption of fats (
steatorrhea, diarrhoea)
• deficiency of lipid-soluble vitamins
• absence of amylase and peptidases
• mostly compensated by stomach and intestinal
enzymes, malabsorption of sugars and AA thus
clinically insignificant
• hypocalcaemia and hyperphosphatemia (due to
 vit. D)  osteomalacia
• deficit of vit. B12 (due to deficit of protease its
release from dietary sources low)  anaemia
• pain
• secondary diabetes mellitus (destruction
of islets of Langerhans)
• complications
• cysts, closure of ducts, leak of juice to
peritoneal and pleural cavity
Cystic fibrosis (mucoviscidosis)
• monogenic (AR) disease due to mutation in gene encoding “cystic
fibrosis transmembrane conductance regulator” (CFTR)
• >600 known mutations in one of the 4 classes
• I – defective protein (preterm stop of translation of CFTR mRNA )
• II – increased degradation of protein in endopl. reticulum (incl. the most common
mutation ∆F508 ~70%)
• III – inactivated channel
• IV – defect of transport
• function of CFTR
• encodes a complex protein forming chloride channel
• regulates other channels (e.g. Na)
• CF affects
• epithelia of respiratory tract
• viscous secret, limitation of respiration and coughing, terrain for infection
(Pseudomonas aeruginosa)  chron. bronchitis, bronchiectasis, pneumonia
• epithelia in pancreatic ducts
• recycling of Cl involved in secretion of HCO3
- into pancreatic juice  due to
decreased bicarbonate too viscose protein secret blocking ducts(chron. pancreatitis)
• sweat glands
• decreased reabsorption of Cl (diagnostic sign - high Cl in sweat)
• intestine
• meconic ileus of newborns
• liver and biliary tract
• genitals
Tumours of pancreas
• most commonly adenocarcinoma
•  risk
• chron. pancreatitis
• smokers
• chron. alcoholism
• typically head and body, less often caudal pancreas
• signs
• obstructive icterus (compression of biliary duct)
• pancreatic insufficiency
• thrombophlebitis
• very poor prognosis
• tumours of endocrine pancreas
• insulinoma (hypoglycemia)
• gastrinoma (Zollinger-Ellison syndrome)
• VIPoma (diarrhea, hypokalemia)
• carcinoid
LIVER DISEASES
Anatomy and histology of liver
• liver (hepar) ~1.5kg
• 2 lobes (sin. and dx.) divided by ligament
• liver parenchyma has characteristic architecture
• liver lobule is a basic morphologic unit
• central vein lobule
• peripheral portobiliar “trias”
• liver acinus is basic functional unit
• part of the tissue supplied by branches of one circumlobular vein
• functions of the liver
• complex metabolic function
• saccharides
• glycogen synthesis, glycogen lysis, gluconeogenesis
• lipids
• clearance of lipoproteins, synthesis of cholesterol, synthesis of
TAG
• proteins
• trans- and de-amination of AA, protein synthesis (albumin,
clotting factors)
• formation of bile
• metabolisms of haem
• biotransformation, detoxification
• hormones, drugs, toxins, ammoniac from intestine
• storage of vitamins and trace substances
Liver blood supply
• v. portae (80% of blood supply)
• drainage from splanchnic organs (= functional
supply)
• capillaries from stomach, intestine, pancreas and spleen
connect in portal vein
• its branches encircle liver lobules (v. interlobulares and
circumlobulares)
• they enter them as liver sinusoids
• sinusoids join to form central vein
• a. hepatica (20% of supply)
• branch of truncus coeliacus (= nutritional supply)
• drain to sinusoid and then to the central vein
• v. hepatica
• drainage from liver
• central veins connect to right and left liver vein leading
to lower vena cava
Liver sinusoids – from portal triad to central vein
Morphology of liver – hepatic lobule
Liver lobule vs. portal lobule vs. acinus
A concept of „liver acinus“ helps to explain „zonality“ of
the liver parenchyma/hepatocytes as a function of O2
availability, nutrients, hormones etc.
Buňky jater – RES a hepatocytes
• RES
• endothelia
• Kuppfer cells (macrophages)
• hepatic stellate cells (Ito cells)
• cholangiocytes
• hepatocytes
• both hepatocytes and
cholangiocytes participate in liver
regeneration
Liver sinusoids
Markers of liver damage/disease
• tests of excretory function
• bilirubin (serum and urine)
• total, conjugated, unconjugated
• tests of liver „cytotoxicity“
(enzymes)
• AST/ALT
• markers of typically active
inflammation/ damage
• uninformative for estimation of residual
functional capacity of liver
• GMT/ALP
• obstruction of biliary tract
• GMT specifically increased in alcohol
abuse
• tests of synthetic function
• total protein
• albumin
• sensitive marker of chronic disease
• globulin
• ratio A/G
• prothrombin time (PT vs. INR)
• extremely sensitive marker of both
acute and chronic liver disease
• complex marker of insufficient formation
o factors 1, 2, 5, 7, 9, 10 in individuals
without K vitamin deficiency, warfarin,
thrombophilia etc.
• tests of detoxifying function
• ammonia
• urea
• tests of storage function
• iron metabolism parameters
• B12
Aetiology of liver damage
• infection
• viral
• hepatitis viruses (HAV, HBV, HCV, …)
• inf. mononucleosis (EBV)
• bacterial
• leptospirosis
• parasite
• Echinococcus
• globally, Europe - Mediterranean
• Schistosomiasis (= bilharzias)
• Africa, J. America, Caribbean, SE Asia
• malaria
• toxic
• alcohol
• faloidin (Amanita faloides)
• drugs (e.g. paracetamol)
• chemicals
• metabolic disorders
• common - NAFLD
• rare
• heredit. hemochromatosis
• Wilson disease
• porphyria
• glycogenosis
• autoimmune
• autoimmune hepatitis
• prim. biliary cirrhosis
• primary sclerosing cholangitis
• tumours
• primary (hepatocellular carcinoma, HCC)
• metastases
Liver infection – viral hepatitis
• time course
• acute
• usually without residual damage
• fulminant form leading to liver failure
• chronic
• only persistent infection (carriers)
• necrosis of parenchyma and progression to cirrhosis
• viral hepatitis
• hepatitis A (HAV – RNA virus)
• only acute time course
• virus directly cytotoxic
• epidemic
• faecal-oral transmission (vaccination)
• hepatitis B (HBV – DNA virus)
• blood borne (parenteral) and STD
• time course
• virus is not directly cytotoxic, damage is the results of the reaction of
immune system
• mostly acutely without residual damage
• in 10% of cases progresses to chronicity
• either solely HBsAg positive carriers
• or active process leading to fibrosis and cirrhosis)
• hepatitis C (HCV – RNA virus)
• blood born (parenteral) and STD
• acute phase typically asymptomatic
• more than 80% cases progress to chronicity – can lead to cirrhosis
Despite variable aetiology, liver reaction t damage
always proceeds through the same stages
• liver reacts the same way to
various aetiologies of
damage
• mild damage change
metabolic activity of
hepatocyte, which become
to cumulate fat (=
steatosis)
• steatosis with lab. signs of
inflammation is called
steatohepatitis
• more severe damage leads
to cell death, however liver
has a considerable ability to
regenerate
• long-term damage leads to
production of connective
tissue in periportal areas (=
fibrosis)
• combination of intensive
necrosis, fibrosis and
regeneration significantly
altering lobular architecture
is called cirrhosis
Reaction of liver to damage
(Painting: Christian Griepenkerl's
Prometheus Tortured by the Eagle, 1800's)
Issue of reversibility - liver regeneration
• sources of cells
• (1) intrinsic liver cells
• hepatocytes
• cholangiocytes
• progenitor/stem cells
• regenerative potential depends on
• location (zones 1 - 3)
• extent of damage or hepatectomy
• hypertrophy
• hyperperplasia
• dedifferentiation in progenitor
cells
• trans-differentiation of
cholangiocytes into
hepatocytes
• (2) mesenchymal stem cells?
(1 -2) Initial (reversible) liver damage
• (1) steatosis (S)
• normally fat content (TAG) in hepatocytes <5%
• histologically microvesicular or macrovesicular
• causes
• excessive dietary intake or lipolysis in adipose tissue
• increased endogenous synthesis
• decreased catabolism in liver
• combination
• steatosis itself is not harmful for liver (sometimes is even considered protective mechanisms),
however it represents substrate for increased lipid peroxidation
• (2) steatohepatitis (SH)
• together with S also necrosis, inflammation and fibrosis
• more serious than simple S (which is reversible when causing factor ceases)
• it can reverse to normal or progress to fibrosis or cirrhosis
• transition of S to SH enhanced by other factors such as oxidative stress, endotoxin, immune
system, nutrition etc.
• aetiology S a SH
• alcoholic
• energetic content of alcohol
• alteration of intermediary metabolism
• inhibition of -oxidation
•  NADH and acetyl-CoA ( synthesis FFA)
• non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH)
• component of insulin resistance syndrome
•  lipolysis in adipose tissue –  uptake of FFA by liver
•  peroxidation of lipids and ox. stress for hepatocytes
• hypeinsulinemia stimulates synthesis of FFA and TAG
Central role of liver in lipid metabolism
Alcoholic steatosis - ethanol metabolism
• oxidative
• by enzyme alcohol dehydrogenase (ADH,
85%) to acetaldehyde
• toxic intermediate acetaldehyde undergoes
conversion to acetate (to Krebs cycle)
• this conversion requires NAD+ (to NADH) and
changes redox state in liver
• mismatch of NADH/NAD+ is essential because it
blocks gluconeogenesis and beta-oxidation of
FFA with subsequent increase lipogenesis (FFA
formation) and their esterification to TAG and
thus steatosis
• by catalase
• by MEOS
• non-oxidative
• formation of molecules called fatty acid
ethyl esters (FAEEs) from the reaction of
alcohol with fatty acids–weak organic acids
that play functional roles in human cells
• enzyme phospholipase D (PLD), which
breaks down phospholipids (primarily
phosphatidylcholine) to generate
phosphatidic acid (PA)
Metabolic consequences of ethanol
detoxification by ADH
• ethanol degradation inhibits
gluconeogenesis
• in alcoholic patients, this problem is
often compounded by a low intake of
carbohydrates
• clinically manifest hypoglycaemia
with unconsciousness is a well-known
and potentially dangerous
complication in alcohol addiction
• hence alcoholic ketoacidosis
• consequently, fatty acid synthesis
is activated in hepatocytes as a
metabolic compensation to
ensure energy substrates
• at the same time, FA oxidation is
inhibited by the lack of NAD+
NAFLD and NASH
• prevalence 20 - 30% in industrialised countries (associated with
OBESITY!!!)
• can be difficult to dissect from alcoholic damage in countries where alcohol
consumption is socially accepted and common
• definition of non-alcoholic aetiology: daily intake <10g/day in men (i.e.
~140g ethanol per week) and (~70g ethanol in women)
• pathogenesis of NAFLD/NASH = metabolic alterations resulting in hepatic
triglyceride accumulation in insulin-resistant states
• insulin resistance is manifested by hyperinsulinemia, increased hepatic
glucose production, and decreased glucose disposal
• in adipocytes, hyperinsulinemia increases hormone-sensitive lipase (HSL)
activity, resulting in elevated rates of triglyceride lipolysis and enhanced
FFA flux to the liver
• FFAs can either be oxidized in the mitochondria to form ATP or esterified to produce
triglycerides for storage or incorporation into VLDL particles
• in liver, hyperinsulinemia induces SREBP-1c and ChREBP expression,
leading to the transcriptional activation of all lipogenic genes and the
enzymatic machinery necessary for the conversion of excess glucose to
fatty acids
• a consequence of increased fatty acid synthesis is increased production of
malonyl-CoA, which inhibits CPT-1, the protein responsible for fatty acid
transport into the mitochondria
• thus, in the setting of insulin resistance, FFAs entering the liver from the
periphery, as well as those derived from de novo lipogenesis, will be
preferentially esterified to triglycerides.
• ACL, ATP citrate lyase; CPT-1, carnitine palmitoyl transferase-1; FAS, fatty
acid synthase; LCE, long-chain fatty acyl elongase
• NAFLD represent good terrain for lipid peroxidation due to oxidative stress
• ox. stress in ins. resistance ( resistin, TNFa, IL-6 and other proinflammatory
adipokines)
• products of lipid peroxidation – malondialdehyd (MDA) or 4hydroxynonenal
(HNE) – stimulate Kuppfer and HSC to fibroproduction
and chemotaxis of neutrophils
Many ways to fatty liver (viral, dietary, alcohol,
T2DM, drugs, …)
(3) More advanced (reversible?) liver damage
• result of chronic damage of hepatocytes
• infection, alcohol, toxic substances, accumulation of
metals (Cu, Fe), drugs, …
• collagen in normal liver
• I and III in periportal areas
• IV in Disse space
• (3) fibrosis (F) = increased content of
connective tissue
• damaged hepatocyte activate Kuppfer cells which
release paracrine factors (PDGF and TGF-)
• activation of hepatic stellate cells (HSC)
• regulation of blood flow through sinusoids ( resistance)
• synthesis of connective tissue (collagen, laminin, …)
• release of photolytic enzymes (matrix-metaloproteinases)
• alteration of morphology of sinusoids (loss of
fenestrations of endothelia), accumulation of
extracel. matrix
Activation of HSC in fibrosis
/cirrhosis • HCS activated by growth
factors from damaged
hepatocytes and Kuppfer
cells
• synthesis of collagen I and
III in Disse space
• loss of microvilli of
hepatocytes
• loss of fenestration of
sinusoids (= capilarisation of
sinusoids)
Alcohol and liver - endotoxin
• alcohol increases permeability for endotoxin from intestine to
circulation
• endotoxin is a part of the G-negative bacteria wall
• endotoxin (via receptors CD14 and TLR4) activates Kuppfer cells
(specialized macrophages along liver sinusoids) to production of
cytokines (NFkB) and superoxide (NADPH oxidase)
Role of HSC in l. fibrosis on hepatic sinusoidal cells
Pathophysiological differences between
normal (A) and fibrotic/cirrhotic (B) liver
• In normal liver (A), normal fenestrae along the hepatic sinusoids allow
free passage of blood (arrows) into the Space of Disse, in which, stellate
cells (green) are found. In liver cirrhosis (B), there is an increase in the
number of stellate cells, associated with deposition of collagenous fibers
in the Space of Disse, and loss of fenestrae as the sinusoids become
more capillary-like. As a result, transfer of low-molecular-weight
compounds (e.g. contrast medium) from the sinusoids into the Space of
Disse becomes more impeded (small arrows).
(4) Advanced (ireversible) liver
damage• cirrhosis (C)
• irreversible (?) change of architecture
(lobules, vessels, collagen)
• parallel processes: steatosis + inflammation
+ fibrosis + necrosis + nodular regeneration
• not so much pure loss of functional parenchyma
but disconnection of functional hepatocytes
from liver circulation
• increased pressure in portal circulation =
portal hypertension
• need for shunting between portal and systemic
circulation by-passing the liver
•  risk of carcinoma
• histologically (diagnosed form liver
biopsy)
• micronodular
• typical for alcohol, primary biliary cirhosis,
hemochromatosis
• macronodular
• typical for viral, autoimmune hepatitis, drugs,
toxins, Wilson disease, ...
• clinical correlate:
• none – compensated cirrhosis
• liver failure – decompensated cirrhosis
Clinical course of liver cirrhosis
Liver failure
• cause
• progression of chronic liver disease = cirrhotic
• acute fulminant hepatitis, intoxication etc. = non-cirrhotic
• signs and symptoms
• weakness, weight loss
• hyperbilirubinemia or icterus (jaundice) due to intrahepatic cholestasis and destruction of
hepatocytes
• portal hypertension
• ascites, splanchnic congestion,
• bleeding
• due to deficit of clotting factors and low K vitamin resorption
• due to thrombocytopenia caused by bleeding, hypersplenism
• oedema, ascites due to hypoalbumiemia
• prolonged action of hormones due to decreased degradation of circulating hormones
• aldosterone
• loss of K by urine, intracel. acidosis, metabolic alkalosis
• decreased ionization of NH3!!!!
• androgens – increased conversion to oestrogens in periphery
• gynecomastia in men
• spider nevi
• liver encephalopathy due to hyperamonemonia and abnormal AA metabolism
• impaired urea cycle
•  conc. of aromatic AA – atyp. neurotransmitters in CNS
• anaemia due to suppression of bone marrow
• metabolic consequences
• disorder of glucoregulation
• hepato-renal syndrome
• due to low effective circulating volume (congestion, ascites, oedemas) and subsequent
activation of RAAS
• hepato-pulmonary syndrome
• pulmonary congestion and subsequent ventilation/perfusion mismatch
Hyperbilirubinemia/icterus
Portal hypertension
• normal pressure in portal circulation 5 – 15 mmHg
• pressure gradient to v. cava is extremely low, therefore, any change of liver sinusoid diameter has a massive impact on
resistance
• localization of portal hypertension
• pre-hepatic
• thrombosis v. portae, malformation, compression
• intra-hepatic
• due to cirrhosis, parasites
• post-hepatic
• right heart failure (hepatosplenomegaly), thrombosis of liver veins (Budd-Chiari syndrome), compression by
tumour
• increased pressure before liver sinusoids does not create pressure overload for liver, after
sinusoids it does, therefore damage is greater
Portal hypertension
• 1) congestion of blood in the v. portae and stasis of
blood in splanchnic organs
• stomach and intestine
• malnutrition and maldigestion
• erosion and ulcers
• increased permeability for bacteria
• spleen - splenomegaly
• hypersplenism  destruction of Ery and platelets
• 2) blood flow through portosystemic shunts /
anastomoses directly to systemic circulation
• normally there are small veins
• under the high pressure risk of mechanical damage and
bleeding
• vv. oesophageae (esoph. varices)
• vv. rectales (hemoroids)
• vv. paraumbilicales (caput Medusae)
• 3) ascites and edemas
• fluid in peritoneal cavity due to portal hypertension +
hypoalbumiemia + retention of Na (aldosterone)
• increased permeability for bacteria = spontaneous bact.
peritonitis
• 5) hepatorenal syndrome
Oesophageal varices
Liver encephalopathy
• abnormalities of conscience (quantitative and
qualitative), behaviour and neuromuscular
functions
• reversible only in initial stages
• mechanisms
• (1) impaired detoxification of ammonia in urea cycle
• sources of ammoniac
• oxidative de-amination by glutamatdehydrogenase from Glu
• glutaminase from Gln to Glu
• degradation of purines and pyrimidines
• de-amination by monoaminooxidase
• synthesis of hem
• bacteria in large intestine
• ammoniac >50mol/l toxic for CNS
• in blood as NH3/NH4+
• balance depends on pH (normally 99% ionised)
• alkalosis increases free ammoniac and thus toxicity
• urea (= ornithin) cycle in liver dally produces 20 – 40 g urea
• CO2 + NH4+  CO(NH2)2 + H2O + 2H+
• 5 enzymes – mitochondria and cytosol
• urea excreted by kidney
• (2) blood from splanchnic contains not only nutrients but
also toxins (ammoniac, mercaptans, phenols etc.
produced by bacteria)
• if not properly detoxified in liver
• formation of “false” neurotransmitters in brain
• change of behaviour and conscience, “flapping” tremor, apraxia
Impaired balance of excitatory and
inhibitory AA in the brain
Cross-talk of intestine and liver - ammonia
Hepatorenal syndrome
• kidney failure accompanying
liver disease without preexisting
kidney pathology
• aetiology
• Na and water retention
• hyper-aldosteronemia
• however, effective circulating
volume is decreased due to
escape to the third space
(ascites)
• hypoalbuminemia
• decrease of renal perfusion and
GFR
• systemic vasodilation but intrarenal
vasoconstriction
• contraction of afferent arterioles
(RAS)
Liver tumors
• benign
• hemangioma
• hematoma
• malign
• hepatocellular carcinoma
• in 70% consequence of cirrhosis
• prevalence increases
• poor prognosis
• metastases
• colorectal carcinoma, …
Pathophysiology of biliary tract
• cholecystolithiasis (gallstones)
• typically 55-65 yrs ~10% men and ~20% women
• causes – alteration of the ration between bile components
• type of stones
• cholesterol (70-90%)
• pigmented (calcium + bilirubin)
• mixed
• increased concentration of cholesterol
• diet, obesity
• decrease of bile acids and phospholipids
• malnutrition, Crohn disease, resection of ileum
• cholecystitis
• stagnation of bile
• diet, starvation
• complications of cholecystholithiasis
• biliary colic (blockade of d. cysticus)
• extrahetal cholestasis (blockade of d. choledochus)
• inflammation (cholecystitis, cholangoitis)
• acute pancreatitis