Liver Disease

Lecture by Bogush N.L.

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Types of liver disease

• Acute or chronic

• Focal or diffuse

• Mild or severe

• Reversible or irreversible

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3 Structure of the liver lobule

Hepatic bar or plate

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nucleus

Space of Disse

Kupffer cell

Glycogen

granules

canaliculus

Hepatic cell

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Liver functions

• A. Excretory function (bile) + role in the

pigment metabolism

• B. Metabolic + detoxificating functions

• C. Barrier function

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A. Pigment metabolism.

RBC Spleen Heme

Senescent +

myoglobin,

catalase,cyto-

chromes

UCB albumin (H2O-insoluble)

LIVER

Splenic, portal veins

CB

bile

urobilinogen

stercobilinogen

Feces - stercobilin (color)

b

a

ct

er

ia

Hemorr.

veins

v.cava inf

kidney

Urine

stercobilin

Intestinal tract

blood

UCB-unconugat-

ed bilirubin

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Bone marrow,

liver

Bile

canaliculus

GT

(GT)

(No GT)

(CB)

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Transformation of bilirubin

Blood UCB albumin

UCB/ albumin

+ glucuronyltransferase

+ glucuronic acids

CB (H2O-soluble)

Smooth

endoplasmatic

reticulum

hepatocyte

Bile canalicules

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Bilirubins in the blood

Total B - 6,8-20,5 mkmol/l

UCB – 75% = 15 mkmol/l

CB – 25% = 5 mkmol/l

Blood bilirubin index – 1/4 - 1/5 (CB:Total B)

Total B > 30-35 mkmol/l ICTERUS:

30-86 – mild

86-170 - moderate

> 171 - severe

CB > 34 mkmol/l bilirubinuria

N

Degree of

severity of

icterus

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Types of Jaundice (Icterus) (from an anatomic standpoint)

• I. Suprahepatic.

• II. Infrahepatic.

• III. Hepatic.

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Bilirubin has a special affinity for elastic tissue (in sclera).

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I. Suprahepatic = hemolytic jaundice

UCB > 35 mkmol/l in blood

icterus (lemon-yellow tint)

CB in bile

urobilinogen

stercobilinogen

in urine in stool UCB>250 mkmol/l

dark urine nuclear (in brain)

icterus encephalopathy No UCB in urine: it is bind +

albumin and H2O-insoluble + anemia= HR,paleness, hypoxia

The gut

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The bile

It contains: bile acids

cholesterol

CB

bicarbonates

lecithin

excretory enzymes:

alkaline phosphatase (AP), 5-nucleotidase, gamma-glutamyl-transpeptidase (GGTP).

micella

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II. Infrahepatic=mechanical jaundice

N UCB in bloodLIVER CB

BILE------ intestinum

into the blood= no bile=

cholemia acholia

stone,

tumor,scar,

cholestasis intestinum

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Cholemia and acholia

BILE X intestinum – no bile!

Bile in blood=cholemia acholia

excretory CB bile acids ADEKF

enzymes CNS heart-vessels: colorless vitamins

icterus asthenia BP, HR feces,

(greenish tint) foaming skin meteorism,

+ urine itching constipation,

dark urine bacterial overgrowth,

(no stercobilin) steatorrhea,creatorrhea

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Cholemia

1)excretory + 2)CB + 3)bile acids

enzymes

icterus skin heart CNS

(greenish tint) -vessels

itching asthenia

dark foaming urine BP

(no stercobilin) HR

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III. Hepatic jaundice

N UB liver (intrahepatic I cholestasis)

UB bile in GUT=

CB = hypo/acholia

Cholemia hepatocellular insufficiency

icterus signs of cytolysis

(ochre color) indicator enzymes (in blood)

AsAT, AlAT,LDG – from cytoplasm,

GDG,MDG – from mitochondrion

+ In blood

Ornitin-carbamiltransferase –

specific liver enzyme Glutamat, malat-

dehydrogenase

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Hepatic pathways

for protein

metabolism and

conversion of

ammonia to urea.

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B. Metabolic function (1)

N disfunction

Proteins.

Synthesis of amino acids in blood

in urine

Synthesis of albumins in blood,

Ponc edemata

Synthesis of

clotting factors hemorrhage syndrome

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Hepatic

pathways

for lipid

metabolism

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B. Metabolic function (2)

N disfunction

Lipids.

Synthesis: of cholesterol ;

of HDLP ;

of bile acids absorption

of lipids in intestinum

+ maldigestion

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Hepatic pathways for glucose metabolism. 27

B. Metabolic function (3)

N disfunction

Carbohydrates.

Synthesis of glucose , hypoglycemia;

Synthesis of glycogen , hypoglycemia.

Depot of vitamins .

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В. Detoxification.

• 1. UB CB

• 2. NH3(from proteins) ornithin circle urea

• 3. Toxins from GIT – phenol, scatol, indole

• 4. Ethyl alcogol aldehyde

• 5. Some medical drugs

• 6. Hormones – aldosteron, ADH, estrogens

(insulin, thyroxin)

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C. Barrier function.

• 1. Cleans the blood from intestinal tract,

spleen, total body.

• 2. Kupffer cells – remove antigens,

immune complexes ( allergy), bacteria and

their toxins.

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Etiology of liver diseases

Primary Secondary

Inborn defects Infections (viruses)

toxins (chemical)

tumors

inflammation

autoimmune disorders

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Pathophysiological syndromes I-XVII

• I. Hepatomegaly.

• II. Hepatosplenic syndrome:

size of the liver and the spleen (they have

common blood and lymphatic outflow,

innervation, system of phagocytes).

• III. Hypersplenism:

Destruction of RBC,L,Planemia, leukopenia,

thrombocytopenia.

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№ IV, V

• IV. Asthenovegetative syndrome:

weakness, fatigue, malaise, depressed mood

bile acids, toxins.

• V. Dyspeptic syndrome:

bad appetite, bitter eructation, flatulence,

constipation intoxication (CNS) +

disorders of digestion in GIT.

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№ VI, VII (1)

• VI. Hemorrhagic syndrome:

1)synthesis of clotting factors in the liver, 2) thrombo-cytopenia, 3) activation of fibrinolytic system.

• VII. Portal hypertension: Phydrostatic in portal vein. Types:

1. Infrahepatic block. 2.Suprahepatic block (right ventricular heart failure). 3.Intrahepatic block (in 70% is caused by cirrhosis of liver).

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№ VII (2)

• Portal hypertension: symptoms and

syndromes:

1. Intoxication (due to blood shunting).

2. Hepatomegaly.

3. Splenomegaly/hepersplenism.

4. Decreased nutrition and body mass.

5. Ascites.

6. Varicosity of the veins.

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№ VII (3)

• Phenomena of shunting.

3 porto-caval shunts:

1. Skin anastomoses (“Medusa head”).

2. In esophagus – can cause a death due to

bleeding from damaged varicose veins.

3. Varicosity of hemorrhoid veins.

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№ VIII

• VIII. Ascites: accumulation of fluid in

the abdominal cavity. Mechanism:

1. Phydrostatic on venous end of capillaries;

2. Poncotic ( albumins);

3. lymph production (from 8-9 l N per day

to 15-20 l), “crying liver”;

4. RAAS + ADH.

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№ IX, X

• IX. Pain syndrome in the right infracostal area: extension of fibrous membrane of the liver, stones in the gall bladder…

• X. Cholestasis: a) partial bile in the intestine. b) dissociated – only CB or only bile acids are retained; c) total cholemia/acholia.

Primary = intrahepatic (cause – in the liver).

Secondary=extrahepatic (cause – in the bile ducts)

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№ XI, XII

• XI. Acholia. No bile acids in the intestine.

active lipase, no emulcification of fat, no

formation of micells (FFA+bile acids),

bicarbonates and pH bad fat digestion and

absorption STEATORRHEA (fat in feces)

+ fat-soluble vit ADEK and F (some FFA) in

organism.

• XII. Cholemia.

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№ XIII, XIV (1)

• XIII. Icterus (with lemon-yellow, orange or green tint).

• XIV. Hepatocellular insufficiency.

1. Carbohydrate metabolism: glycogen store

hypoglycemia, glucuronic acid inadequate detoxication.

2. Protein metabolism: albumins edemata;

dysproteinemia alb/glob, ESR; aminoacids aminoaciduria; urea, ammonium.

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№ XIV (2)

clotting factors I,II,V,IX,X,XIII hemorrhagic

syndrome, blood prothrombin index;

transferrin synthesis + B12 deficiency anemia;

hormonal imbalance aldosteron, estrogenes.

3. Lipid metabolism: chlesterol and bile acids.

4. barrier function of the liver: allergy, toxemia

till a toxic shock.

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№ XV

• XV. Liver failure.

Pathogenetic forms:

1. Excretory (cholestatic); acute

2. Hepatocellular; or

3. Vascular; chronic

4. Combined.

Types: absolute/relative; total/partial; minor/major.

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Acute liver failure. Causes.

• Intoxication with acetaminophen

• Autoimmune hepatitis

• Hepatitis A

• Hepatitis B

• Hepatitis C

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Clinical features of acute LF

• Jaundice, icterus + cholestasis

• Encephalopathy

• Coagulopathy

• Portal hypertension (intrahepatic origin) + ascites

and encephalopathy

• Hepatorenal syndrome ( Na retention, water excretion,

renal perfusion, glomerular filtration rate) due to systemic

vasodilation, vasoconstriction of afferent renal arterioles

and renin-angiotensin activity.

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Chronic liver failure. Causes.

• Chronic hepatitis B

• Chronic hepatitis C

• Non-alcoholic fatty liver diseases

• Alcoholic fatty liver diseases

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Clinical features of chronic LF

• Anorexia, weight loss, weakness

• Jaundice, encephalopathy, coagulopathy

• Pruritus (itching)

• Portal hypertension (esophagogastric varices,

splenomegaly + hypersplenism, platelet count)

• Hyperestrogenemia (palmar erythema, spider angiomas

of the skin, hypogonadism and gynecomastia)

• Predisposition to hepatocellular carcinoma

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№ XVI (1)

• XVI. Hepatic coma.

Syndrome developing with absolute, total

( all functions), major (with

encephalopathy) liver failure.

Causes: severe viruses hepatitis, toxic

dystrophy, cirrhosis, portal hypertension…

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№ XVI (2)

The main feature is encephalopathy due to

intoxication.

In blood: cerebrotoxins – ammonium,

phenol, indol, scatol…bile acids…derivates

of pyruvic and lactic acids…FFA…. some

aminoacids…… false neurotransmitters

(octopamine, -phenilethylamine – disturb

synaptic transmission).

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№ XVII

• Extrahepatic symptoms:

pallor (anemia), signs of scratching on the skin (cholemia), xanthomatosis (cholesterol metabolism disorder),

telangiectasias (“vascular spiders”) - pulsating angiomas (0,5-1 sm), palmar erythema (“hepatic palms”), raspberry tongue, gynecomasty estrogens.

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