Liver Cirrhosis

Irreversible damage due to chronic/advanced liver disease

At least 70- 80% of liver replaced by fibrous tissue

Etiology:

– Chronic alcoholism

– Chronic hepatitis (viral hepatitis B, C)

– Primary biliary cirrhosis (autoimmune)

– Haemochromatosis

– Alpha-1 antitrypsin deficiency,

Pathophysiology and Clinical Manifestations

Low albumin, ascites, peripheral edema

Portal hypertension, esophageal varices, splenomegaly, caput medusa

Increased bilirubin, Jaundice

Bleeding tendencies

Manifestations of increased estrogens:

– Gynecomastia

– Impotence

– Infertility

– Loss of sexual drive

– Testicular atrophy

Fetor hepaticus

Skin manifestations:

– Spider nevi, palmar erythema

Hepatorenal syndrome:

– Renal failure due to advanced liver disease

Hepatic encephalopathy:

– Neurologic manifestations of impaired cognitive function

– Flapping tremor (results from ammonia crossing blood brain barrier of the brain)

Portal hypertension (review anatomy of liver and portal circulation)

↑pressure in portal system due to resistance to portal blood flow

Etiology:

Pre-hepatic: portal vein thrombosis or congenital atresia

Intrahepatic: liver cirrhosis, hepatic fibrosis, massive fatty change, military TB

Post-hepatic: obstruction at any level between liver and heart; thrombosis in hepatic vein or IVC, constrictive pericarditis

Pathophysiology:

Open portosystemic collaterals

Systemic venous congestion

Reduced blood flow to liver

Toxic substance pass directly to systemic circulation

Clinical manifestations/complications:

Bleeding varices in lower esophagus, stomach

Splenomegaly

Ascites

Hepatic encephalopathy

Hepatorenal syndrome

Gallbladder Diseases

Obstruction

Inflammation (cholecystitis) and the most common

Cholelithiasis: gallstone formation

Gall Bladder Stones

Risk factors:

Obesity

Middle age

Female

Native American ancestry

Pathophysiology:

Most common is the cholesterol and pigmented stones

Theories:

– Enzyme defect increases cholesterol synthesis

– Decreased secretion of bile acids to emulsify fats

– Decreased reabsorption of bile acids from ileum

– Gallbladder hypomotility and stasis

– Genetic predisposition

Obesity at a Glance

Body mass index (*BMI) > 30

Regulation of body weight:

– Hypothalamus

– Hormones controlling appetite/weight:

o Insulin

o Leptin

o Ghrelin

o Adiponectin

A major cause of morbidity, mortality and increased health care costs

*Starvation & Malnutrition

Decreased caloric intake leading to weight loss and eventually cachexia

Short-term starvation can be compensated by:

– Glycogenolysis

– Gluconeogenesis

Long-term starvation leads to malnutrition disorders:

– **Marasmus

– **Kwashiorkor

Cancers of the Gastrointestinal Tract

Esophagus

Stomach

Liver

Gallbladder

Pancreas

Colon cancer

Important for all cancers:

– Risk factors

– Screening

– Precancerous lesions

Gluten-Sensitive Enteropathy (Celiac Disease)

A type of malabsorption syndrome

Impaired absorption due to mucosal sensitivity to gluten

Etiology:

Dietary, genetic, and immunologic factors

Pathophysiology:

Gluten is the protein component in cereal

grains (BROW; Barley, Rye, Oat and

Wheat)

Acts as a toxin that damages villous

epithelium in small intestine

Associated with other autoimmune

disorders (IgA deficiency)

Clinical manifestations:

Manifestations of malabsorption symptoms

Failure to grow and thrive

Confirmation by a tissue biopsy

Celiac crisis:

– Severe diarrhea, dehydration

Biliary Atresia

Congenital malformation characterized by absence or obstruction of intrahepatic or extrahepatic bile ducts

Pathophysiology/ Clinical manifestations:

– Block, inflammation, and fibrosis of the bile canaliculi

– Cholestasis

– Jaundice is the primary clinical manifestation

– 80% die before 3 years if untreated

– Liver transplant long-term therapy

Kwashiorkor and Marasmus

Both are:

– Known collectively as protein energy malnutrition (PEM)

– Types of malnutrition associated with long-term starvation

Pathophysiology:

Kwashiorkor: a severe protein deficiency

Marasmus: a deficiency of all nutrients

Impaired liver function:

– In kwashiorkor, the lack of proteins causes the liver to swell because of the inability to produce lipoproteins for cholesterol synthesis

– In marasmus, liver function still continues, but the overall caloric intake is too low to support cellular protein synthesis

Clinical manifestations:

Manifestations of malnutrition

Stunted physical and mental development

The presence of subcutaneous fat, hepatomegaly, and a fatty liver (kwashiorkor) differentiates kwashiorkor from marasmus

End of Module