SG2 CASE PRES: EDEMA

Dr. Sei Tugade| Oct 3, 2020

TABLE OF CONTENTS To compute alcohol in grams: (Total ml x 0.008 x %proof)
1. Case
2. Impression Alcohol density d=0.8g/ml. Thus: a wine at 12.5 % vol contains
3. Alcoholic Liver disease 12.5ml of alcohol/100ml of wine x 0.8 g/ml = 10g of alcohol/100 ml
4. Differential Diagnosis of wine.
5. Alcoholic cirrhosis This is the equivalent of 1 drinking unit (= 10 g). This way it is
easy to assess the number of units you are consuming.
CASE ON EDEMA
REVIEW OF SYSTEMS
GENERAL DATA 1. GENERAL:
Case of 43 years old male WEIGHT GAIN (15% in 3 months), (-) fever, (-) cold,
(-) headache
CHIEF COMPLAINT 2. HEENT:
Pedal Edema Head: (-) Pain, (-) Limitation Of Movement
HISTORY OF PRESENT ILLNESS Eyes: (+) YELLOWING OF SCLERAE,(-) Tearing,
(-) Itching, (-) Discharge, (-) Pain, (-) Diplopia, (-) Drynes
3 months PTC, the patient started to note a gradual increase in Ears: (-) Pain
abdominal girth, as evidenced by tightening of his belt and clothes. He Nose: (-) Pain, (-) Itching, (-) Colds
also noted swelling of his legs and feet and tightening of his shoes. Mouth And Throat: (-) Soreness, (-) Pain, (-) Hoarseness
Since then, he was noted to have lost his appetite and was generally Neck: (-) Pain
weak. There were occasions when he felt nauseated, but never 3. RESPIRATORY:
vomited. Persistence of symptoms prompted consult. (-) Cough, (-) Dyspnea,(-) Hemoptysis,(-) Cyanosis,
(-) Nasal Congestion
What are the pertinent questions that you should ask your patient 4. CARDIOVASCULAR:
when presented with bipedal edema or increasing abdominal (-) Chest Pain, (-) Palpitations, (-) Orthopnea, (-) Dyspnea,
girth? First think of organ systems that can be involved: cardiac, (-) Easy Fatigability,(-) Known Cvd
liver, GI pathologies, lymphaedemas so u can ask symptoms 5. GASTROINTESTINAL:
from those organs (+) NAUSEA, (-) Vomiting, (+) VAGUE RUQ PAIN,
(-) Hematemesis,(-) Diarrhea,(-) Dysphagia,(-) Jaundice,
What other associated symptoms can u ask the patient if youre (-) Fresh Blood In The Stool,(-) Mass
considering Cardiac or Liver? You can ask orthopnea, easy 6. GENITOURINARY:
fatiguability, ask duration of other symptoms as well not just the (-) Dysuria,(-) Polyuria,(-) Gross Hematuria
chief complaint. 7. MUSCULOSKELETAL:
(-) Decreased In Sensation
How will you ask orthopnea? 8. NERVOUS:
Orthopnea: Difficulty of breathing in supine position (-) Dizziness, (-) Loss Of Consciousness (-) Seizures,
(-) Head Trauma, (-) Tremors
PAST MEDICAL HISTORY
He was treated for PTB in the year 2000. He took Isoniazid, PHYSICAL EXAMINATION
Rifampin,Pyrazinamide, Ethambutol for 6 months. He has no past 1. VITAL SIGNS:
medical history of hypertension, DM, asthma, goiter and heart ✓ BP -110/80mmHg
disease. He also denies any allergies and has no previous ✓ HR- 72bpm
hospitalizations nor previous surgeries. ✓ RR-18,breaths/min
✓ TEMP- 36.8C
FAMILY HISTORY 2. GENERAL SURVEY:
His father is hypertensive while his mother is diabetic. Apart from Patient is awake, conscious, coherent, and not in cardio-
those, there was no other diseases like asthma, allergies, goiter and respiratory distress. His weight is 80kg, height is 164cm and his
heart disease. BMI is 29.8 kg/m2(overweight).
3. HEENT:
PERSONAL AND SOCIAL HISTORY Pink Conjuctiva, (+) ICTERIC SCLERAE, (-) Cervical
He is a 40 pack year smoker and is a heavy alcohol drinker. He Lymphadenopathy, (-) anterior neck mass, (-) tonsillopharyngeal
consumes 10-12 bottles of beer and 1 bottle of gin daily for the congestion, JVP = 6cm
past 8 years. He is former construction worker, unemployed for the 4. CHEST AND LUNGS:
past 8 years. Separated for the past 6 years, lives with siblings in (+) GYNECOMASTIA, ECE, CBS, (-) rales/wheezes
Tondo. 5. CARDIOVASCULAR:
Apex Beat = PMI 5th ICS LMCL, good S1 and S2, (-) S3 gallop,
How can you tell that drinking hx is pertinent? What is the Normal rate and regular rhythm, (-) murmur
relevant drinking hx for you to develop chronic liver dses from 6. ABDOMEN:
drinking? Standard threshold in drinking shld consist of 1 bot. of Globular abdomen with abdominal girth 102cm, (+) SPIDER
beer, 4 ounces of wine 1oz of spirit ANGIOMATA, (+) FLUID WAVE, normal active bowel sounds,
Males: 60-80g per day dull on percussion, tense, liver span 12 cm RMCL, LIVER
Women: 20-40g per day EDGE FIRM PALPABLE 3CM BELOW THE R SUBCOSTAL
MARGIN, (+) OBLITERATED TRAUBE’S SPACE,(+) DIRECT
How to compute alcohol in grams? Alcohol intake should be RUQ TENDERNESS (-) rebound tenderness
presented in grams. 7. EXTREMITIES:
Pink nailbeds, (+) PALMAR ERYTHEMA, full equal pulses, (+)
GRADE 3 PITTING BIPEDAL EDEMA, (-) cyanosis
DEPARTMENT OF INTERNAL MEDICINE
IMPRESSION DIFFERENTIAL DIAGNOSIS
ALCOHOLIC CIRRHOSIS
If youre creating an impression, u wont say alcohol cirrhosis
right away, you can only see cirrhosis one you have the aid of
youre ultrasound or CT scan. What do u think is a better
impression?? Alcohol Liver disease.

RATIONALE
• History:
– Increase in abdominal girth
– Swellings on his legs and feet
– Heavy alcohol drinker
– Former construction worker
– Lives in Tondo
– Fatigue
• PE and ROS
– Globular abdomen with abdominal girth 102cm,
– Gynecomastia
– (+)spider angiomata, (+)Fluid wave
– Dullness on percussion
– Tense, liver span 12cm RMCL, Liver edge palpable
3cm below the R subcostal margin
– (+)Oblterated Traube’s space
– (+)Direct RUQ tenderness
– (+)Palmar erythema
– (+) grade 3 pitiing bipedal edema
– (+)yellowing of sclerae, vague RUQ pain,weight
gain(15% in 3 months)

EPIDEMIOLOGY
• Alcohol is the world’s third largest risk factor for disease burden.
• The harmful use of alcohol results in 2.5 million deaths each year.
• Most of the mortality attributed to alcohol is secondary to
cirrhosis.
• These increases in cirrhosis and its complications are closely
correlated with increased volume of alcohol consumed per capita
population and are regardless of gender.

ALCOHOLIC LIVER DISEASE

• Chronic and excessive alcohol ingestion is one of the major
causes of liver disease.
• The pathology of alcoholic liver disease consists of three major
lesions
1. Fatty liver
2. Alcoholic hepatitis
3. Cirrhosis
• Quantity and duration of alcohol intake are the most important PATHOPHYSIOLOGY
risk factors

Alcoholic liver disease. The interrelationships among hepatic • Basically, once the alcohol gets to your stomach, most of it
steatosis, alcoholic hepatitis, and alcoholic cirrhosis are shown, along is sent to the liver for processing.
with depictions • In very small amounts – alcohol is more or less harmless
of key morphologic features. It should be noted that steatosis, • But in excess – can lead to serious liver complications
alcoholic hepatitis, and steatofibrosis may also develop
independently. In particular some patients present initially with
cirrhosis without any of the other forms of alcoholic liver disease
2
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“Go home and plant kamote.”
DEPARTMENT OF INTERNAL MEDICINE
ALCOHOL METABOLISM • Excessive fat in the liver is also known as FATTY CHANGE/
FATTY LIVER/ STEATOSIS
– Characterized by a large, heavy, greasy, and yellowish
– But at this point = patient is asymptomatic

• Deficiency of NAD: main cause of the accumulation of fat in

the liver
• Increase in NADH/NAD ratio – also causes lactic acidosis

• Once alcohol enters the hepatocytes – it can take one of the 3

pathways/enzyme systems.
• All these pathways lead to the conversion of alcohol to
acetaldehyde.

3 Enzyme Systems: Metabolism of ethanol by CYP2E1 / MEOS produces reactive

- Cytosolic ADH – majority of ethanol oxidation
- Microsomal ethanol oxidizing system (MEOS)
- Peroxisomal catalase
- Acetaldehyde highly reactive molecule may have multiple effects
- Direct product of alcohol oxidation
oxygen species (ROS)
↓
Lipid peroxidation of hepatocyte cell membranes
• Looking back at the different pathways, when you make
acetaldehyde from alcohol – also start to generate ominous
compounds called ROS.
• These ROS react with different components of the hepatocyte,
and can cause serious damage to the cells.

• Once the ADH enzyme is utilized for the conversion of alcohol, it

needs another compound called NAD.
– Alcohol oxidation by ADH causes the reduction of nicotinamide
adenine dinucleotide (NAD+) to NADH
NAD
– Required for fatty acid oxidation
– For conversion of lactate into pyruvate
• Acetaldehyde binds with macromolecules, enzymes, or any other
cellular component = Acetaldehyde adducts
• These compounds subsequently activates the immune system.
• The immune system would now start sending neutrophils to the
site of damage.
• As cells become inflamed and damaged, patients develop
alcoholic hepatitis.

Acetaldehyde adducts
↓
Immune system activation
↓
Neutrophilic infiltration
↓
Inflamed liver
ALCOHOLIC HEPATITIS

• As NADH levels increase and NAD levels decrease Mallory-Denk bodies

→ 2 scenarios happen: o Damaged intermediate filaments
1. Higher NADH levels signal the cell to start producing more o Mechanism unclear
fatty acids o Associated with ALCOHOLIC HEPATITIS
2. Lower NAD levels result in less fatty acid oxidation
• Both of which lead to more fat production in the liver

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“Go home and plant kamote.”
DEPARTMENT OF INTERNAL MEDICINE
• In Histopathology, we can • When liver cells are injured, they come together and form
start to note a change in the regenerative nodules
cells, and notice bundles of – Regenerative nodules
proteins called Mallory- • One of the classic signs of cirrhosis
Denk bodies. • More bumpy as opposed to a smooth,
• These bodies are damaged healthy liver
intermediate filaments, • Between these nodules, are fibrotic tissue and collagen
located in the cytoplasm of
hepatocytes.
• Mechanism is unclear.

How do these bands of fibrotic tissue form though?

• Fibrosis is a process mediated by special cells called stellate

cells – sit b/n the sinusoid and hepatocyte (perisinusoidal space)
• Basic layout of the functional unit of the liver: portal vein, hepatic
artery that combine into a sinusoid
• Portal triad: portal vein, hepatic artery, bile duct
• In a normal setting, stellate cells are usually quiescent or sort of
dormant.
• When these hepatocytes are injured, they secrete paracrine
factors that “activates” and changes the stellate cells.
• Once activated, these stellate cells proliferate, and start secreting
TGF B1 – which causes them to produce collagen (main
ingredient in extracellular matrix, fibrosis, and scar tissue.
• As fibrotic tissue builds up, it starts to compress the central veins
and sinusoids – leading to portal hypertension. And this is when
complications due to cirrhosis start to crop up. (Next slide)

Steatosis and Hepatitis are reversible while cirrhosis isn’t

anymore. Repeated exposure/injury leads to cirrhosis

ALCOHOLIC CIRRHOSIS
When cells are injured or damaged (due to excess amounts of
alcohol) and die off
↓
Fibrotic
(Thickened with heaps of protein)
↓
Scar tissue formation

• Higher portal vein pressure means that fluid in blood vessels is

more likely to get pushed into tissues and across tissues into
large open spaces like the peritoneal cavity. That’s why cirrhosis
leads to excess peritoneal fluid = ascites.
• Other complications are manifested as well, such as congestive
splenomegaly and hypersplenism – becomes enlared because
all this fluid and blood can’t get into the liver, and backs up into
the spleen.

4
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“Go home and plant kamote.”
DEPARTMENT OF INTERNAL MEDICINE
• In the same way, the circulatory system starts diverting blood
away from the liver because of the high liver pressures – also
known as portosystemic shunt.
• Blood flow follows the path of least resistance and shunts away
from the portal system and towards the systemic circulation.
• In this case, somebody with cirrhosis might not have any
symptoms, or have nonspecific symptoms like weight loss,
weakness, or fatigue.
• Later on, though, with extensive scarring, the liver progresses
to decompensated cirrhosis, and can’t function properly.
• At this point many of the described symptoms start to develop,
like jaundice and pruritus or itchy skin, ascites, hepatic
encephalopathy leading to confusion, and easy bruising from
low coagulation factors.
• For diagnosis, the “gold standard” is a liver biopsy, taking a tiny
sample of the liver tissue examine under a microscope.

CLINICAL FEATURES
• The diagnosis of alcoholic liver disease requires accurate
history regarding both amount and duration of alcohol
consumption.
• Nonspecific symptoms
✓ Vague RUQ abdominal pain
✓ Fever
✓ Nausea and vomiting
• As you have less and less of these basic liver functional units,
✓ Diarrhea
your liver becomes less and less able to do its job of
✓ Anorexia
detoxification.
✓ Malaise
• When your liver isn’t detoxifying your blood, these toxins can get
• More specific complications of chronic liver disease
into the brain and start causing mental deficits, a condition known
✓ Ascites
as hepatic encephalopathy.
✓ Edema
• Although there are several neurotoxins that are thought to ✓ Upper Gastrointestinal (GI) Hemorrhage
contribute to the development of these mental changes, the best
• Other clinical manifestations
understood factor is ammonia in the blood, which is produced
✓ Jaundice
mainly in the gastrointestinal tract; usually the liver plays
✓ Encephalopathy
a vital role in removing ammonia and stopping it from going into
the systemic circulation.
• As more of these and other toxins get into the brain, patients
might develop asterixis, where they have tremoring or jerky
hands when outstretched, and as even more toxins build up,
eventually patients can progress to a coma.
• Also, since the liver plays a big role in metabolizing estrogen into
inactive metabolites that can be removed from the blood
and excreted, patients can also experience complications due to
increased estrogen in the blood, like gynecomastia, spider
angiomata, and palmar erythema.

• Many cases present incidentally at the time of autopsy or elective

• Since the liver usually conjugates bilirubin,
surgery.
increased unconjugated bilirubin in the blood from a less-
• The abrupt onset of any of these complications may be the first
functional liver can lead to jaundice.
event prompting the patient to seek medical attention.
• Another important job of the liver is producing albumin, so again,
if the liver’s not functioning right, you can have a decreased
Physical examination
amount of albumin in the blood, or hypoalbuminemia.
• Liver and spleen may be enlarged, with the liver edge
• Finally, the liver helps in making clotting factors or proteins that being firm and nodular
help coagulate your blood, so when you aren’t producing Other frequent findings
these coagulation factors, you can develop issues related to your a. Scleral icterus
ability to coagulate blood, which you need in order to stop blood
b. Palmar erythema
loss after an injury.
c. Spider angiomas
• To recap the general symptoms of cirrhosis, early on, with a d. Parotid gland enlargement
small amount of scarring and fibrosis, we call it e. Digital clubbing
compensated cirrhosis, meaning the liver can still do a lot of its f. Muscle wasting
job. g. Development of edema and ascites
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“Go home and plant kamote.”
DEPARTMENT OF INTERNAL MEDICINE
• INR
- Standardizes prothrombin time measurement to assess
synthetic function of liver
• Serum bilirubin
- Derangement in hepatocyte synthetic function indicates more
serious disease.
• Serum albumin
- To assess synthetic function of the liver
• Serum ammonia
- Hypoalbuminemia is more common in chronic liver disorders
such as cirrhosis and usually reflects severe liver damage and
decreased albumin synthesis.
• Blood glucose
- To assess metabolic function of the liver

C. Histopathology
• Liver biopsy
- Most accurate in disorders causing diffuse changes throughout
the liver
Other patients may be identified in the course of an evaluation of - Hepatic lesions uncharacterized by radiologic imaging
routine laboratory studies that are found to be abnormal. - Staging of malignancy

• Men D. Imaging
– Decreased body hair • Ultrasound
– Gynecomastia - Shows space-occupying lesions within the liver
– Testicular atrophy - Patency of circulation
• Women with advanced alcoholic cirrhosis - Size of the liver
– Menstrual irregularities - Presence of mass or cystic lesions
– Amenorrhea - Confirm the presence of ascitis
• These changes are often reversible following cessation of
alcohol ingestion. MANAGEMENT
A. Pharmacologic Management
Laboratory tests: • Complete Abstinence from Alcohol
– Completely normal (early compensated alcoholic cirrhosis) – Disulfiram, Acamprosate, Naltrexone (FDA approved
– Many abnormalities usually are present (advanced liver medications for alcohol dependence)
disease) • Glucocorticoids
• Anemia – Prednisone 40 mg or prednisolone 32 mg daily for 7
– Zieve’s syndrome (severe alcoholic hepatitis) – a unique days
form of hemolytic anemia (with spur cells and – If bilirubin decreases, continue for an additional 21
acanthocytes) days, followed by a 2-week taper
• Platelet counts: Reduced early in the disease – Only for the patients with no active GI bleeding,
• Serum total bilirubin: Normal or elevated with advanced systemic infection, renal insufficiency
disease • TNF inhibitor (Pentoxifylline)
• Direct bilirubin: Frequently mildly elevated in patients with a – Pentoxifylline 400 mg TID for 28 days
normal total bilirubin – For the patients with active GI bleeding, systemic
• Prothrombin times: Often prolonged and usually do not infection, renal insufficiency
respond to administration of parenteral vitamin K B. Non-pharmacologic Management
• Serum sodium levels: Usually normal unless patients have • Lifestyle modification:
ascites and then can be depressed, largely due to ingestion of – Lifestyle changes are key to treating ALC. The most
excess free water. important thing to do is to stop all alcohol intake. This
• Serum Alanine and Aspartate Aminotransferases (ALT, should be done under the supervision of a physician to
AST): Typically elevated, particularly in patients who continue to prevent complications of withdrawal .
drink, with AST levels being higher than ALT levels, usually by a – Smoking speeds up liver damage, so quitting smoking
2:1 ratio. is important.
– Maintaining a normal weight is also helpful. Obesity
LABORATORY WORKUP can cause non-alcoholic fatty liver, which is similar to
A. Diagnostic Test alcoholic hepatitis.
- CBC - Serum albumin – Eating a balanced diet and taking certain vitamins and
- Liver Enzymes - Serum ammonia minerals can correct nutritional deficiencies caused by
- Prothrombin time and INR - Blood glucose alcohol abuse.
- Serum Bilirubin - Ultrasound • Nutritional support:
- Liver biopsy – Protein 1.2-1.5 g/kg
– Recommended caloric intake 2500 kcal/day (oral or
B. Biochemical test NGT feeding)
• Complete Blood Count (CBC) – Nighttime snacks and morning feeding to improve
- Baseline detection of anemia and other abnormality nitrogen balance
• Liver enzymes (AST 7 ALT) • Complete Abstinence from alcohol:
- Sensitive indicator of liver injury – Cornerstone in the management of alcoholic liver
• Prothrombin time disease
-To assess coagulation/synthetic function of the liver – Screen for alcohol abuse (screening tools: AUDIT-C,
CAGE, MAST)

6
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“Go home and plant kamote.”
DEPARTMENT OF INTERNAL MEDICINE
– FDA approved medications for alcohol dependence: • Transient elastography has also been used to stage cirrhosis and
disulfiram, acamprosate, naltrexone has been shown to be useful in predicting complications such as
– Goal of intervention should be sustained abstinence variceal hemorrhage, ascites development and liver-related
What will you advise the patienet regarding the diet knowig the death.
patient has edema and ascites? Salt restriction and limit water
intake. Usually we limit fluid intake into only 1L but ins severe
cases we limit it into 500ml

can we treat the patient with diuretics?

For px with edema, the first line would be diuretics. For patients
with distention, you can do your therapeutic and diagnostic
paracentesis to relieve the patient’s difficulty.

PROGNOSIS
• Once cirrhosis develops, scoring systems are employed to
assess compensated versus decompensated disease and
prognosis.
• The initial staging system used for this purpose was the modified
Child Pugh classification, with a scoring system of 5–15:
– scores of 5 and 6 represent Child-Pugh class A
(consistent with “compensated cirrhosis”),
– scores of 7–9 represent class B
– scores of 10–15 represent class C.
• This scoring system was initially devised to stratify patients with
cirrhosis into risk groups before portal decompressive surgery.
• The Child-Pugh score is a reasonably reliable predictor of
survival in many liver diseases and predicts the likelihood of
major complications of cirrhosis, such as bleeding from varices
and spontaneous bacterial peritonitis.
• This classification scheme was used to assess prognosis in
cirrhosis and to provide standard criteria for listing a patient as a
candidate for liver transplantation (Child-Pugh class B)
• The MELD system provides a more objective means of
assessing disease severity and has less center-to-center
variation than the Child-Pugh score as well as a wider range of
values.
• The MELD and PELD systems are currently used to establish
priority listing for liver transplantation in the United States.
• Convenient MELD and PELD calculators are available via the
internet.
References:
- Harrison‘s Principles of Internal medicine, 20th edition
- Robbins and Cotran: Pathologic Basis of Disease, 9th edition
- https://www.osmosis.org/learn/Cirrhosis
- https://www.osmosis.org/learn/Alcoholic_liver_disease

• More recently, the Child-Pugh system has been replaced by the

Model for End-Stage Liver Disease (MELD) system for the latter
purpose.
• The MELD score is a prospectively derived system designed to
predict the prognosis of patients with liver disease and portal
hypertension.
• Initially, this score was calculated from three noninvasive
variables: the prothrombin time expressed as the international
normalized ratio (INR), the serum bilirubin level, and the serum
creatinine concentration.
• The ability of the MELD score to predict outcome after liver
transplantation is regularly monitored and was modified to
increase its accuracy and improve allocation of donated livers.
• These modifications include serum sodium concentration as a
factor in the model and a reweighting of the MELD components.
• A separate scoring system pediatric end-stage liver disease
(PELD) is used for children (<12 years of age).

7
SG5
“Go home and plant kamote.”