Approach To Patient With Hepatic Disorders

Approach to Patient with Hepatic Disorders

Liver Structure and Function largest organ in the body;  weighs about 1-1.5kg  Located in the RUQ of the abdomen under the right lower rib age against the diaphragm 

Blood Supply 20% from Hepatic Artery (oxygenrich) b. 80% from Portal Vein (nutrient-rich) a.

A mixture of venous and arterial blood bathes the liver cells

Hepatic

Portal Vein

Artery

Liver Common capillary bed/ sinusoids of liver

Central Veins of each Lobule

Hepatic Vein Inferior Vena Cava

Liver Cells  Hepatocytes

– 2/3 of liver mass and does most of the liver functions  Kupffer cells – engulf particulate matter (bacteria) that enter the liver through portal blood  Ito cells – fat-storing cells

Functions of Liver

Glucose Metabolism I. Meal

Glucose absorption in intestines

Glucose converted to glycogen

Portal Circulation

Stored in hepatocytes

II. Exercise

Protein/Fat breakdown

Liver creates glucose (gluconeogenesis)

Liver

Ammonia Conversion Ammonia from: use of amino acids from protein for gluconeogenesis

Ammonia from: production of intestinal flora/ from diet

Portal Circulation

Liver: converts ammonia to urea

Systemic circulation

Excreted in the kidneys (urine)

Protein Metabolism  Synthesizes

plasma protein

(albumin, alpha and beta globulin)

 Clotting

factors (prothrombin)

- liver needs Vit. K to synthesize prothrombin

Fat Metabolism  Fatty

acids are degraded into ketone bodies for energy during hypoglycemic state, starvation and uncontrolled DM.

Vitamin and Iron Storage  Large

amounts of Vit. A, B, and D and several B-complex vitamins are stored in the liver  Iron and copper are also stored in the liver

Drug Metabolism First-pass Effect Oral meds pass the G.I.T.

Portal circulation

Liver (metabolized)

Decreased bioavailability

Bioavailability – fraction of drug that reaches the systemic circulation

Bile Formation  Formed

by the hepatocytes  Primary bile acids are cholic acid and chenodeoxycholic acid (CDCA)  Major components: water(82%), bile acids(12%), lecithin &other phospholipids (4%) and unesterified cholesterol (0.7%)

Bilirubin Excretion Degradation of Senescent RBC’s in the spleen

Release of Hemoglobin Heme molecule

Biliverdin reductase

Heme oxygenase

CO & biliverdin

bilirubin

Enterohepatic Circulation Bile (conjugated bilirubin) Bile ducts duodenum Ileum and colon (converted into urobilinogen) Excreted in feces (stercobilin)

Reabsorbed into portal circulation Systemic circulation kidney Excreted in urine

Liver: reexcreted into bile

Clinical History

 Symptoms

of Liver Disease  Nature of Disease  Pattern of Onset  Disease Progression  Potential Risk Factors

Symptoms of Liver Disease Fatigue - most common characteristic of liver disease e.g. lethargy, weakness, restlessness B. Nausea/Vomiting – provoked by odor of food or fatty food intake C. RUQ pain/discomfort – arises from stretching/irritation of Glisson’s capsule w/c A.

D. Pruritus/Itching – related to accumulation of bile salts in the dermis E. Jaundice – hallmark of liver disease and most reliable marker of severity - accompanied by acholic tools/ tea-colored urine? e.g. jaundice without dark urine indicates unconjugated hyperbilirubinuria

Nature of Disease Hepatocellular

injury vs. Cholestatic injury

Hepatocellular: ALT/AST elevated out of proportion to alkaline phosphatase Cholestatic: Alkaline phosphatase out of proportion to ALT/AST Viral

vs Bacterial ( Viral Hepatitis/ Liver abscess)

Pattern of Disease (Staging)  Course

of disease (acute vs. chronic)  Early vs. late  Pre-cirrhotic, cirrhotic, end stage

Disease Progression (Grading)  Severity

and activity of disease  Active vs. inactive; mild moderate, severe

Potential Risk Factors A. 

Alcohol consumption



Assess presence of abuse or dependence Alcoholism – defined on behavioral patterns and consequences of alcohol intake not on the basis fo amount of consumption.

for women: 2 drinks(22-30g/day) for men: 3 drinks (33-45g/day)

Abuse – repetitive pattern of drinking alcohol that has adverse effects on social, family, occupational and health status Dependence – alcohol-seeking behavior despite its adverse effects

C

Have you ever felt you ought to Cut down on drinking?

A

Have people Annoyed you by criticizing your drinking?

G

Have you ever felt Guilty or bad about your drinking?

E

Have you ever had a drink first thing in the morning to steady your nerves and get rid of hangover? Eye-opener

B. Medications 

Currently taking meds? on maintenance drugs? Herbal medicines? Birth control pills? Self-medication? Illicit drug use?

C. Lifestyle       

Personal habits/hygiene Eating habits/food preference Sexual activity/preference Recent travel Environment/sanitation/occupation Tattoe, piercing, needle-stick injury Exposure/contact with patients with liver disease

D. Past Medical History    

Previous hospitalizations Previously acquired diseases Recent surgery Blood transfusions

E. Family History 

Related familial diseases of the liver

Physical Examination

A. Icterus  Assess

•

for these areas:

sclerae (under natural light) skin ( for fair-skinned individuals) oral-mucosa ( for dark-skinned individuals) Clinically evident when serum bilirubin exceeds 2.5mg/dL

Types of Jaundice A. Hemolytic - increased destruction of red

blood cells e.g. transfusion reactions, Hemophilia B. Hepatocellular – inability of damaged liver cells to clear normal amounts of bilirubin from the blood e.g. viral hepatitis, cirrhosis C. Obstructive – occlusion of bile duct by gallstone, inflammatory process, tumor or enlarged organ (extrahepatic) - obstruction of small bile ducts within the liver (intrahepatic)

B. Spider Angiomata 

superficial tortous arterioles typically fill from center outwards usually seen on arms, face and upper torso. C. Palmar Erythema

D. Hepatomegaly/Splenomegaly

liver size varies; not a reliable sign of liver disease  Palpation: assess liver edge for unusual firmness, irregularity and nodules. 

E. Hepatic Tenderness  Most reliable P.E. finding  Discomfort/pain on touching/pressing

F. Ascites

accumulation of excess fluid within the peritoneal cavity  Percussion: shifting dullness (+) abdominal fluid wave 

G. Hepatic Encephalopathy Accumulation of ammonia due to damaged liver cells fot to brain dysfunction  P.E. : a. changes in personality, sleep patterns, irritability, mental dullness (not due to meds, F&E imbalance, etc.) b. asterixis/flapping tremors of body and tongue c. Fetor hepaticus – sweet ammonial odor, fruityodor of breath 

* Trail-making test – N=15-30secs

H. Others • • •

•

•

Umbilical Hernia – due to ascites Caput Medusa – collateral veins seen radiating from umbilicus Hyperpigmentation/Xanthelasma- tendon xanthomata due to increased lipids and cholesterol Kayser-Fleischer rings- golden brown copper pigment deposited at periphery of cornea. Hepatic Bruit – sound produced in lung CA.

Diagnostic Procedure

i. Lab Tests/Liver Function Tests a. b. c. d. e. f.

Pigment studies Protein Studies PT Serum Aminotransferases GGT,LDH Cholesterol Studies

a. Pigment Studies Measures

the ability of the liver to conjugate and excrete bilirubin

Serum bilirubin (direct) 0-0.3mg/dL (total) 0-0.9mg/dL Urine bilirubin 0(0) Urine urobilinogen 0.05-2.5mg/24hr Fecal urobilinogen 40-200mg/24hr

b. Protein Studies Albumin: cirrrhosis chronic hepatitis edema, ascites Globulin: cirrhosis liver disease chronic obstructive jaundice viral hepatitis A/G ratio is reversed in chronic liver disease

c. Prothrombin  Normal

100% or 12-16secs  Prolonged in liver disease

d. Serum Aminotransferases A. ALT (SGOT) 10-40units - to monitor coure of hepatitis/cirrhosis and effects of treatments that may be toxic to liver - Increased : liver disorder b. AST (SGPT) 5-35 units - present n tissues high in metabolic activity (heart, liver, skeletal muscle) - increase with damaged tissues

e. GGT/ LDH  Elevated

in alcohol abuse  Marker for biliary cholestasis

f. Cholesterol Studies  Elevated

in damaged liver Normal values: HDL M: 35-70mg/dL F: 35-85mg/dL LDL <130µg/dL

ii. Diagnostic Imaging

a. US/CT scan  First

option for suspected obstructive jaundice  Can also detect fatty liver

b. ERCP  Both

diagnostic (biliary tree visualization) and therapeutic ( stone extraction, stents)  Extrahepatic cholestasis: dilated ducts  Intrahepatic cholestasis: ducts not dilated

c. Doppler US/MRI  Asses

hepatic vasculature and dynamics

iii. Liver Biopsy

 Gold

standard in evaluation of liver disease

Alcoholic Liver Disease

 due to chronic, excessive alcohol ingestion Fatty liver b. Alcoholic hepatitis c. Cirrhosis a.

Alcoholic Cirrhosis (Laennec’s)  An

irreversible chronic injury of the hepatic parenchyma and extensive fibrosis in association of regenerative nodules

ii. Clinical Manifestations  



Anorexia, malnutrition, wt. loss Sx of hepatocellular dysfunction: jaundice, portal hypertension, bleeding varices, ascites, encephalopathy Hormonal disturbances: Men: gynecomastia, testicular atrophy Women: virilization, menstrual problem

iii. Lab Findings 

   

Anemia – due to G.I. blood loss - coexistent nutritional deficiency (folic & B12) Elevated transaminases Prolonged PTT – reduced synthesis of clotting proteins; Vit. K Decreased serum albumin – impaired protein synthesis Increased ammonia levels – may lead to encephalopathy

iv. Prognosis 

Abstinence to alcohol consumption decreases morbidity/mortality and delays/prevents complications

Major Complications

a. Portal Hypertension  Normal

pressure in portal vein ( 5-10mmHg); PH is > 10mmHg  Damaged liver structures leads to increased resistance to portal blood flow (presinusoidal, postsinusoidal & sinusoidal venous compartments)  In Cirrhosis, resistance is usually at sinusoidal area

portal venous system has no valves

facilitates retrograde blood flow from high pressure portal venous system to a lower pressure systemic circulation

Cardioesophageal

Rectum

junction

Esophagogastric varices

hemorrhoids

Retroperitoneal space

Falciform ligament of liver

ascites

Periumbilical/abdominal wall collaterals (caput medusa)

b. Esophageal Varices i. 

 



Factors to Bleeding: Muscular exertion from lifting heavy objects; straining at stool, sneezing, coughing or vomiting. Esophagitis Irritation of vessels by poorly chewed foods or irritating fluids; reflux of stomach contents salicylates

ii. Treatment: 

 

Life- threatening EMERGENCY!!! - replacement of blood loss to maintain intravascular volume BEFORE Dx studies and interventions to stop bleeding (hemostasis) *** excessive fluid administration would increase portal pressure leading to further bleeding Close monitoring of CVP, urine output, mental status Only when hemodynamically stable should we proceed to Dx procedure and hemostasis

iii. Medical Management: c.

Vasoconstrictors:

•

Vasopressin – generalized vasoconstriction leading to decreased blood flow to portal venous system Somatostatin/Octreotide – direct splanchnic vasoconstriction

•

b. Balloon Tamponade - tube introduced to the stomach, gastric balloon inflated and pulled back into the stomach cardia. - done if bleeding is too vigorous and endoscopy is not available e.g. triple lumen (SengstakenBlakemore)

c. Endoscopic Intervention – first line of treatment to control bleeding acutely. c.i. Endoscopic Sclerosis – varices injected with sclerosing agents via a needle- tip catheter passed through the endoscope c.ii. Endoscopic Band Ligation – varices are ligated with endoscopically placed small elastic O-rings

d. non-selective beta adrenergic blocker – causes hypotension and eventually causes hypovolemia.

iv. Surgical Management b. Portal-systemic shunt – to permit decompression of the portal system Non-selective – decompresses entire portal system Selective – decompresses only the varices while maintaining blood flow to the liver.

c. Ascites Accumulation

of fluid in the peritoneal space Signs and Symptoms: Increased abdominal girth/ rapid weight gain  Short of breath – due to enlarged abdomen  Striae/distended veins  Fluid and electrolyte imbalance *** assessment based on the s/sx to assess progression of the disease 

Cirrhosis with portal hypertension

Splanchnic arterial vasodilation

Continued arterial underfilling

Persistent activation of systems for retention of sodium and water; ascites and edema formation

Decreased in circulating arterial blood volume

hypervolemia

Activation of reninangiotensin and SNS and ADH

Kidney retains sodium and water

Management: b. Dietary Modification - low sodium diet (2g/d NaCl) - to create a (-) Na balance leading to diuresis e.

Diuretics

•

Spironolactone (Aldactone) first line of treatment for ascites from cirrhosis Furosemide – may produce hyponatremia with prolonged use Ammonium Chloride/Acetazolamide – contraindicated (precipitates hepatic coma)

• •

*** daily wt. loss should not exceed: 1-2kg in patients with ascites/edema 0.5-0.75kg in patients without edema *** fluid restriction is not attempted unless Na is very low Complications:  Fluid and electrolyte imbalance  Encephalopathy – due to hypovolemia and dehydration  Decrease potassium = increased ammonia in systemic circulation

c. Bed Rest - upright posture promotes activation of RAAS system leading to decreased GFR, Na excretion and decreased response to loop diuretics d. Paracentesis

d. Hepatic Encephalopathy A

complex neuropsychiatric syndrome characterized by these 4 major factors:

• • • •

Hepatocellular disease/portal systemic collateral shunts Disturbances of awareness and mentation Shifting combinations of neurologic signs: asterixis,rigidity,hyperreflexia A characteristic symmetric high voltage triphasic slow wave pattern on ECG

Hepatocellular dysfunction Shunting of portal venous bood into systemic circulation

Liver is bypassed

Metabolic abnormalities in the CNS

Toxic substances not detoxified by liver

*** Ammonia not converted to urea

Accumulation in systemic circulation

Common Precipitants  Increased

Load

-

Nitrogen

Gastrointestinal bleeding Excess dietary protein Azotemia Constipation

 Electrolyte

-

and

Metabolic imbalance Hypokalemia Alkalosis Hypoxia Hyponatremia hypovolemia

 Drugs -

Narcotics Tranquilizers Sedatives diuretics

 Miscellaneous -

Infection Surgery Superimposed acute liver disease Progressive liver disease Portal-systemic shunts

Stag Mental Status e Euphoria or depression, I

Asterixi s

+/-

Triphasic waves

II

Lethargy, moderate confusion

+

Triphasic waves

III

Marked confusion, incoherent speech, sleeping but arousable Coma; initially

+

Triphasic waves

-

Delta waves

mild confusion, slurred speech, disordered sleep

IV

responsive to noxious stimuli, later

EEG

Treatment:  Elimination

or treatment of precipitating factors  Lowering of blood ammonia levels by decreasing the absorption of protein and nitrogenous products from the intestine