JaundiceTranscribed from the lecture of Dr. NgoSection D 2011 - Mikey Silverman

Jaundice Yellow discoloration of the skin, sclera, and mucous membranes as a

result of an elevated serum bilirubin concentration. Learning Objectives

To review and understand bilirubin metabolism To learn the differential diagnosis of jaundice To learn the subjective and objective data to be gathered in a patient

with jaundice.

Differential Diagnosis (3 types) Isolated disorders of bilirubin metabolism

Unconjugated hyperbilirubinemia Increased bilirubin production

Hemolysis, ineffective erythropoiesis, blood transfusion, resorbption of hematomas

Decreased hepatocellular uptake Drugs (rifampicin), Glibert’s syndrome

Decreased conjugation Glibert’s syndrome, Crigler-Najjar syndrome

Conjugated or mixed hyperbilirubinemia Dubin-Johnson syndrome Rotor’s syndrome

Liver Disease Hepatocellular dysfunction

Acute or subacute hepatocellular disease Viral hepatitis, alcohol, drugs, hypotension, metabolic disorders

(Reye’s syndrome), pregnancy-related Chronic hepatocellular disease

Viral hepatitis, alcohol, autoimmune hepatitis, metabolic (hemochromatosis, Wilson disease, NAFLD)

Hepatic Disorders with prominent cholestasis Diffuse infiltrative disorders

Granulomatous diseases (TB, sarcoidosis, lymphoma), amyloidosis, malignancy

Inflammation of intrahepatic bile ducts Primary biliary cirrhosis, drugs (erythromycin, TMP-S)

Miscellaneous conditions Drugs (estrogens), TPN, bacterial infections

Obstruction of the Bile Ducts Choledocholithiasis – a stone found at the level of the common bile duct

Hindrance to bile flow Manifests with jaundice, fever, pain Cholesterol/pigment gallstones

Parasites Ascaris, chlonorchis

Diseases of the bile ducts Inflammation/infection (primary sclerosing cholangitis, AIDS

cholangiopathy, hepatic arterial chemotherapy, postsurgical stricture); neoplasms (cholangiocarcinoma)

Extrinsic compression of the biliary tree Neoplasms (pancreatic CA), pancreatitis, vascular enlargement

History Onset Progression Accompanying symptoms

Abdominal pain Fever Pruritis Stool/Urine color Weight loss Pallor GI bleeding

Alcohol consumption Blood transfusion Drug use/abuse Sexual partner/s Travel Family history

Physical Examination Jaundice

at least 51 mol for icteric sclera Vital signs Skin Lymphadenopathy Heart & lungs Abdomen – tenderness, mass, organomegaly, ascites Extremities Signs of Portal Hypertension

Splenomegaly – obliteration of Traub’s space Ascites – shifting dullness, puddle sign Leg edema Caput medusa

Stigmata of Liver Cirrhosis Spider angiomata Palmar erythema Gynecomastia Parotid gland enlargement Testicular atrophy Loss of body hair Dupuytren’s contracture

Liver Function Tests Hepatocellular necrosis

ALT, AST Synthetic Function

Albumin (hypoalbuminemia) Prothrombin time (prolonged)

Cholestasis Elevated:

Bilirubin Alkaline Phosphatase GGTP (together with elevated SGTP, can be sure it is a liver

dysfunction) 5’ Nucleotidase

Imaging studies Ultrasound / EUS MRI / MRCP CT scan PTC ERCP

Clinical Evaluation Jaundice with abdominal pain & fever

Hepatocelluar carcinoma Hepatobiliary TB Amoebic liver abscess Benign CBD obstruction with cholangitis (stone, stricture, ascaris) Malignant CBD obstruction with cholangitis (pancreatic CA) Acute pancreatitis

Jaundice with abdominal pain, no fever Benign CBD obstruction without cholangitis (stones, structures, ascaris) Malignant CBD obstruction without cholangitis (pancreatic CA) Hepatocellular CA Metastatic CA to the liver

Jaundice without abdominal pain, with fever Leptospirosis Typhoid fever Malaria Sepsis Collagen diseases

Jaundice without abdominal pain & fever Acute hepatitis (viral, drug, alcohol) Chronic hepatitis Cirrhosis Congenital hyperbilirubinemia Malignant Obstruction of CBD

Approach to Patients with Hematologic DiseaseSection D 2011 - Mikey Silverman

Findings Leading to hematological Consultation RBC – Anemia, Polycythemia, Nucleated RBC’s WBC – Leukopenia/Leukocytosis, Lymphocytosis, Immature

Granulocytes Platelets – Thrombocytosis/Thrombocytopenia Lymphadenopathy/Splenomegaly Others

Exaggerated bleeding: spontaneous/trauma related, abnormal PT/aPTT

Leg Pain/Deep Vein Thrombosis History

General symptoms Performance status Weight loss Fever Fatigue/malaise/lassitude Weakness

Specific Symptoms By system

Performance Status Determines the physiologic reserve of the patient

i.e. Karnofsky performance scaleRating Definition

100 Percent No evidence of disease

90 Percent Normal activity with minor signs of disease80 Percent Normal activity with effort; signs of disease70 Percent Cannot do normal activity but cares for self60 Percent Requires occasional assistance50 Percent Requires considerable assistance; frequent medical care40 Percent Disabled, requires special care30 Percent Severely disabled; hospitalization may be indicated20 Percent Very sick; hospitalization necessary for supportive treatment10 Percent Moribund0 Percent Death

General Symptoms Weight loss

Frequently seen in many serious diseases including primary hematologic entities

Significant unintentional weight loss (5% body weight over 6-12 months)

Fever Elevation of body

temperature that exceeds normal daily variation

Increase in the hypothalamic set point

Mean oral temp: 36.8 +/- 0.4oC

Occurs in: Early

manifestation of aggressive lymphoma/acute

leukemia Accompanying immunodeficiency Other malignancies

Fatigue/malaise/lassitude Difficult to assess Maybe explained by fever and muscle wasting in patients with severe

diseases Weakness

Accompany malignant processes Manifest as a general loss of strength/reduced capacity for exercise Hematologic disease

Myeloma/lymphoma: central/peripheral nervous system invasion/compression

Specific Symptoms Nervous system

Headache Paresthesias Confusion Impairment of consciousness

Eyes Conjunctival plethora Diplopia

Ears Vertigo Tinnitus

Neck Painless swelling Diffuse swelling of the face

Chest/Heart Dyspnea and palpitations Cough Chest pain

Nasopharynx, oropharynx, oral cavity Epistaxis Anosmia/olfactory hallucination Sore tongue Macroglossia Gingival hyperplasia Dryness of mouth Dysphagia

Gastrointestinal system Abdominal fullness/discomfort Malabsorption Diarrhea Constipation

GU/Reproductive system Impotence/bladder dysfunction Hematuria Priapism Menorrhagia

Back/Extremeties Arthritis Hemarthroses Bone pain

Skin Pallor Bronze/grayish pigmentation

Cyanosis Jaundice Erythromelalgia Pruritus Petechia/ecchymoses

Personal and Environmental History Drug History Sexual History Occupational Exposure

Benzenes Organophosphates Herbicides

Nutrition Dietary deficiencies

Family History Hematologic disorders

Jaundice History of gallstones History of venous thromboembolism History of hemophilia

Ethnic background Past Medical History

Operations Previous transfusions

Physical Examination Pertinent body systems

Skin Pallor/flushing

Skin color is caused by the pigment contained therein and by the blood flowing through the capillaries

Mucous membranes, conjunctivae, palmar creases Cyanosis

Function of total amount of reduced hemoglobin May be influenced by skin pigmentation

Jaundice Observed in the skin of individuals who are not otherwise deeply

pigmented Caused by ble pigment (direct/conjugated bile)

Petechiae Small (1-2mm) round lesions from hemorrhages into the skin Present in areas of high venous pressures No blanching on pressure

Ecchymoses Various shapes and sizes Blanches with pressure

Excoriations Nails

Koilonchia Eyes

Jaundice Pallor Retinal hemorrhages/exudates Dilation of veins

Mouth Pallor Ulceration of oral mucosa Bleeding Tongue: macroglossia

Lymph nodes Cervical,

supraclavicular, axillary, epitrochlear, inguinal, femoral

EXTENT (localized/generalized)

SIZE TEXTURE TENDERNESS

Skeleton Spleen

Usually non palpable Other methods:

Traube’s Nixon’s Castelo

Liver Nervous system

Cerebral impairment, visual impairment, cranial nerve dysfunciton

POEMS (polyneuropathy, organomegaly, endocrinopathy, multiple myeloma, skin changes)

Joints Deformities: repeated hemorrhages

Edema/Urinary Complaints/Female GenitaliaSection D 2011 - Mikey Silverman

I. Approach to patient with kidney and urinary tract diseaseII. Edema

III. Discolored Urine – hematuriaIV. Abnormalities of Urine VolumeV. Renal and Ureteric Colic

VI. Symptoms related to the act of urinationVII. Symptoms of bladder outlet obstruction/prostatism

VIII. Urinary incontinenceIX. Female genital examination

I. Approach to Patient With Kidney and Urinary Tract disease Primary renal disease Secondary renal disease Disease of the urinary tract

Anatomic localization of the Lesion Kidneys

Glomerulus Tubules Interstitium Vascular System

Lower urinary tract Ureter Bladder Urethra

Cross-section of the kidney

Means of Discovery1. Symptomatology2. PE3. Laboratory abnormalities

II. Edema Palpable swelling produced by expansion of the interstitial fluid volume Localized or generalized ANASARCA – gross, generalized edema Recognized in its generalized form by puffiness of the face and

indentation of the skin following pressure (pitting edema)

2 basic steps for edema formation:1. Alteration in capillary hemodynamics2. Dietary Na and water retention by the kidneys

Major causes of edema according to primary mechanism 1. Increased capillary hydraulic pressure

Increased plasma volume due to renal Na+ retention Heart failure, including cor pulmonale

Primary renal sodium retention Renal disease, including the nephrotic syndrome Drugs: minoxidil, diazoixide, thiazoilidinediones, calcium channel

blockers, NSAIDs, fludrocortisone, estrogens Early hepatic cirrhosis

Pregnancy and premenstrual edema Idiopathic edema

Venous obstruction Cirrhosis or hepatic venous obstruction Acute pulmonary edema Local venous obstruction

2. Hypoalbuminemia Protein loss

Nephrotic syndrome Protein-losing enteropathy

Reduced albumin synthesis Liver disease Malnutrition

3. Increased capillary permeability Idiopathic edema Burns Trauma Inflammation or sepsis Allergic reaction, including certain forms of angioedema Adult respiratory distress syndrome Diabetes mellitus Interleukin-2 therapy Malignant ascites

4. Lymphatic obstruction or increased interstitial oncotic pressure Postmastectomy Nodal enlargement due to malignancy Hypothyroidism Malignant ascites

5. Uncertain mechanism Docetaxel Pramipexole

History Where is the edema located? Is the edema persistent or intermittent? Is the edema unilateral or bilateral? Is the edema pitting or non-pitting? Is there a history of any disorder or drug intake that can cause cardiac,

hepatic, renal disease? Pitting edema

Depression that does not rapidly refill and resume its original contour Reflects movement of excess water in response to pressure

Non-pitting edema Lymphedema Pre-tibial myxedema

Principal causes of Generalized Edema

Cardiac

Dyspnea on exertion, orthopnea, PND; edema extensive in the legs and accentuated in the evening

Elevated JVP, S3 gallop, occasionally with displaced or dyskinetic apical pulse, peripheral cyanosis, cool extremities, small pulse pressure when severe

Hepatic

Dyspnea infrequent, except if associated with significant degree of ascites, ethanol abuse

Ascites, JVP normal or low, BP lower than in renal or cardiac disease, signs of chronic liver disease – stigmata of cirrhosis

Renal

Usually chronic, may be associated with uremia – decreased appetite, metallic or fishy taste, altered sleep pattern, difficulty concentrating, restless legs, dyspnea may be present, but less severe than heart failure, bubbly urine

BP may be high, hypertensive or diabetic nephropathy, periorbital edema, pericardial friction rub, nitrogenous fetor, asterexis in uremia

Nephrotic syndrome Periorbital/peripheral edema Ascites Bubbly urine BP normal or elevated CVP normal to high normal Heavy proteinuria (>3.5 g/day) Hypoalbuminemia Lipiduria Hyperlipidemia

III. Discolored Urine – Hematuria Color Pathologic Non-pathologic

White ChylePus

Phosphates

Yellow to orange Bilirubin Concentrated urine

Urobilin RifampicinFood colorCarrotsNitrofurantoin

Read to brown to purple

PorphobilinPorphobilinogenUroporphyrinGlomerular DiseasesExtraglomerular diseases Hemoglobinuria Myoglobinuria

Natural food pigments (beets)Artificial food coloringPhenothiazinesPhenazopyridinesLaxatives(phenolpthalein, senna)

Blue to green

BiliverdinPseudomonas infection

Vitamin B complexPhenyl salicylatesThymolTriamtereneAmvtriptyline

Hematuria Macroscopic (grossly visible) – red or brown urine Microscopic (urinalysis) - >/- 2 RBCs/hpf Origin

Kidney – glomerulus – dysmorphic RBC Ureter Bladder Prostate Urethra Clotting mechanism defect

Etiology

History Color Transient or persistent Partial or total

Partial Initial – anterior urethral lesion (urethritis, stricture, meatal

stenosis) Terminal – posterior urethra, bladder neck, prostate

Total (throughout urination) Above the level of the bladder (stones, tumor, TB, nephritis)

Associated symptoms Frequency, dysuria, urgency, suprapubic pain Flank or CVA pain Passage of wormlike clots

Painful or painless Painless hematuria

Bladder or kidney tumor Polycystic kidneys Acute GN Sickle cell disease Tuberculosis Post-traumatic Post-exercise

Painful hematuria Stones Urinary tract infection Renal infarction

Ingestion of foods containing red vegetable dyes (beets) Medications: aspirin, anticoagulants, laxatives History of recent upper respiratory tract infection Positive family history of renal disease – polycystic kidney disease,

sickle cell, blood dyscrasia Recent vigorous exercise or trauma Travel or residence in areas endemic for Schistosoma haematobium,

or tuberculosis Cyclic hematuria – passage of hematuria during or after menstruation

PE Pallor Petechiae, echymoses, lymphadenopathy, splenomegaly – blood

dyscrasia CVA tenderness and fever – renal infarction Suprapubic tenderness – bladder

Bilaterally enlarged kidneys – PKD AF/valvular heart disease – renal embolism/infarction

IV. Abnormalities of Urine Volume Oliguria/Anuria

Normal load of metabolic waste product cannot be excreted Oliguria – 24-h urine output of < 400-500 mL/day Anuria – complete absence of urine < 50 mL/day Azotemia – retention of nitrogenous waste products (asymptomatic) Uremia – signs and symptoms brought about by azotemia (elevated BUN

and creatinine) dialysis Etiology

Acute renal failure Pre-renal Renal Post-renal

Chronic renal failure (> 3 months; irreversible) Note: non-oliguric renal failure – urine output of >500 mL/day with

acute or chronic azotemia Location of the Cause?

Clinical assessment of ARF Search for reversible factors that may be exacerbating ARF, e.g.,

hypervolemia, ongoing administration of nephrotoxic medications Examine for clinical evidence of uremia (e.g., asterixis, confusion, hiccups,

nausea, vomiting, pericarditis) Clinical assessment of intravascular volume Review most recent laboratory results for metabolic complications:

hyperkalemia, acidosis, hyperphosphatemia Review drug prescription: discontinue all non-essential drugs and adjust

dose or dose interval of drugs eliminated by kidney Review nutritional status: consider protein, salt, potassium and phosphate

restriction: consider need for enteral nutrition or hyperalimentation

Polyuria More than 3L urine/day Etiology

Excretion of non-absorbable solutes (osmolar loads) – glucose, mannitol

Excretion of water – defect in ADH production or renal responsiveness (diabetes insipidus)

History Symptoms of uncontrolled DM Intake of medications

PE – state of hydration

V. Renal and Ureteric Colic Renal Colic

Dull, aching, steady pain in the CVA just lateral to the sacrospinalis muscle and just below the 12th rib

Often unilateral Severe crescendo/decrescendo type of pain Radiates from CVA to hypochondrium (umbilicus) Due to sudden distention of the renal capsule Acute pyelonephritis Acute ureteral obstruction

Ureteral colic Similar characteristic as renal colic Severe colicky back pain that radiates from CVA towards inguinal

ligament into the scrotum or labia majora Acute obstruction – passage of a stone or blood clots

Ureteral stone Proximal ureteral stone – lateral flank to abdominal region; pain

radiates to the testicle (T11-12) Mid portion of the ureter, R side – pain radiates to the McBurney’s

point Midportion of the ureter, L – LLQ Distal ureteral stone – pelvis to inguinal canal/inner

thigh/groin/genitalia Ureterovesical junction – bladder irritability (frequency, urgency)

Caliceal stone Asymptomatic Small, non-obstructing Gross hematuria

Renal pelvis stone Asymptomatic Flank/CVA pain (ureteropelvic junction)

Stones – history Age of onset Family history of stone Fractures/immobilization – hypercalcemia Previous UTI or manipulation Renal or ureteric colic Associated symptoms – nausea, vomiting

Fever and chills (UTI) Gross hematuria – stone passage

Dietary habits/fluid intake Stones – PE

Flank tenderness Tophi

VI. Symptoms related to the act of urination Dysuria

Painful urination Tingling or burning sensation in the perineum during or just after voiding Caused by one of the 2 conditions

Inflammation involving the urethra and bladder trigone Inflammation involving the vaginal labia

Etiology Etiology Location Lower UTI (bacterial) bladder and urethra Acute pyelonephritis upper urinary tract Chlamydial urethritis urethra Gonococcal urethritis urethra Other urethritis urethra No recognized pathogen urethra Vaginitis vagina

History Onset of symptoms Nature of symptoms

Pain intensity Timing

Initial/during urinationUrethritisUrethral obstructionMeatal ulcer

TerminalCystitis (with dull and steady suprapubic pain)Bladder calculiProstatitis/seminal vasculitis

Localization Associated Symptoms

Frequency Nocturia Incontinence Hematuria Pelvic/back pain Fever/chills Vaginal discharge

Last menstrual period Sexual activity, type of contraception, symptoms in partner History of prior urinary or gynecologic symptoms and infections Conditions which might predispose to treatment failure (diabetes,

pregnancy, recent antibiotic treatment, hospitalization, urological instrumentation, urological anatomic anomaly)

Allergy to medications PE

Abdominal examination CVA tenderness – acute pyelonephritis Suprapubic tenderness – cystitis

Genital exam Prostate exam

Frequency Frequent voiding without increased urine flow Decreased voiding interval (<2 hours) Pollakuria – abnormal increased frequency of urination The normal capacity of the bladder is 400 mL Etiology

Residual urine – reduces the functional capacity of the organ Bladder inflammation – infection, stones, tumor Bladder fibrosis – TB, radiation cystitis, interstitial cystitis,

schistosomiasis Urgency

Sudden and compelling desire to pass urine that is difficult to defer Nocturia

Waking at night from sleep to void (>/= 2x) May be a symptom of renal disease due to a decrease in the function of

renal parenchyma with loss of concentrating power Can occur in the absence of disease History

On average, how many times do you wake up at night to void? Fluid intake (24 hour, bedtime, diuretic fluids) Medications (diuretics, xanthines, beta-blockers, cholinesterase

inhibitors) Co-morbid conditions Associated symptoms

Obstructive –hesitancy, weak urinary stream, incomplete emptying, intermittency)

Irritative – frequency, urgency, urinary incontinence PE

Comprehensive PE Enuresis

Nocturnal urinary incontinence Nighttime bed wetting Physiologic during the first 2-3 years of life May be functional or due to delayed neuromuscular maturation of the

urethrovesical component May also be a symptom of organic disease (UTI, distal urethral stenosis

in girls, posterior urethral valves in boys, neurogenic bladder)

VII. Symptoms of Bladder Outlet Obstruction/Prostatism Obstructive symptoms

Hesitancy Loss of force and decrease caliber of urinary stream (weak stream) Dribbling Abdominal straining Intermittency Acute urinary retention Chronic urinary retention Sense of residual urine Cystitis

Prostatism Syndrome which occurs with progressive vesicle obstruction Stages:

1. Early stage (irritability) Bladder musculature begins to hypertrophy Contraction of hypertrophied detrusor muscle is so strong, causing

spasm Urgency and frequency

2. Stage of compensation Obstruction increases, further hypertrophy of bladder musculature Bladder develops contractions strong enough to overcome

resistance at the bladder neck Exhaustion of the detrusor muscle as it nears end of the contraction

phase Urgency and frequency plus hesitancy, loss in force and size of

urinary3. Stage of decompensation

Bladder tone becomes impaired Urethral resistance exceeds detrusor power Inability of the bladder to contract and expel the contents of the

bladder Marked hesitancy, need for straining to initiate urination, very weak

and small stream, acute urinary retention, residual urine, overflow incontinence

Differential diagnosis Obstructive

BPH/prostate CA Vesical neck obstruction Urethral stricture

Functional Detrusor neuromuscular dysfunction Detrusor instability Psychogenic voiding dysfunction

Infectious and Neoplastic Cystitis Bladder CA Prostatitis Prostatic abscess

PE Enlarged kidneys – CVA mass CVA tenderness – infection Palpable bladder – distended bladder Palpation of the urethra – induration (stricture) DRE (Digital rectal examination)

Atony of anal sphincter Enlarged prostate Tender prostate (prostatitis)

Palpation of the posterior surface of the prostate gland. Feel for the lateral lobes and median sulcus

Enlarged Prostate

VIII. Urinary Incontinence Involuntary leakage of urine Urgency – sudden and compelling desire to pass urine that is difficult to

defer Urge Incontinence

Inability to hold urine once the urge to void occurs Secondary to involuntary bladder contractions Causes: cystitis

CNS disorder – upper motor neuron lesion Can be seen in tense, anxious women in the absence of infection

Stress Incontinence Leakage of urine due to increased intraabdominal pressure Involuntary leakage with coughing, sneezing, laughing, running Causes: weakness of bladder neck supports (pelvic floor relaxation);

urethral sphincter damage Unusual in nulliparous women

Overflow incontinence Paradoxical incontinence Loss of urine due to chronic urinary retention or secondary to a flaccid

bladder Mechanical dysfunction resulting from an overdistended bladder Causes

Anatomic obstruction by prostatic hypertrophy and strictures Neurologic abnormalities that impair detrusor contractility (multiple

sclerosis); spinal lesions Symptoms

Weak urinary stream Dribbling Hesitancy Frequency Nocturia

Functional Incontinence Intact urinary tract but factors like cognitive abilities, immobility, or

musculoskeletal impairments lead to incontinence Organic dementia, psychiatric patients

Patients may have more than one type of incontinence at any given time History

Onset and course of incontinence Associated lower urinary tract symptoms Leakage frequency, timing, volume Precipitants (medications, caffeinated beverages, coughing, laughing,

physical activity) Bowel and sexual function Status of other medical conditions and symptoms, along with their

temporal relationship to urinary incontinence onset or worsening Any prior incontinence treatment – surgery Have you leaked urine in the past 3 months? Which precipitants led to leakage? Which precipitant caused leakage most often?

PE Comprehensive PE Abdominal examination – to look for masses and tenderness, distended

bladder Rectal examination – to check for masses and impaction, prostate

consistency and symmetry Genital examination in women – to assess adequacy of pelvic support; to

assess presence of rectocoele, cystocoele

IX. Female Genital Examination External Examination

Inspection and Palpation

Labia Majora Labia Minora Clitoris Urethral orifice Vaginal introitus Skene and bartholin glands Muscle Tone

Draped patient in dorsal lithotomy position

Separation of the Labia

Palpation of Skene Glands Palpation of Bartholin Glands

Palpating the Perineum

Cystocele Rectocele

Internal Examination Use a speculum – cervix

Bimanual Examination Cervix Uterus Adnexa and ovaries

Rectovaginal examination Anal sphincter Rectal walls and rectovaginal septum

Examination of internal genitalia with speculum

Bimanual palpation of the uterus

Bimanual palpation of adnexa, sweep abdominal fingers downward to capture ovary

Rectovaginal Examination Anal sphincter Rectal walls and rectovaginal septum Uterus Adnexa Stool

Rectovaginal examination