Liver and Biliary System

• Reminder: anything water soluble digested by the GI tract go through the liver 1st

  • so ammonia

• Under normal system portal vein should NOT be connected to systemic veins

• Great defense against bacterial infections thought to be due to specialized phagocytes (Kupffer cells)

  • All infections except those with hepatotrophic viruses are rare in the US

  • Bacterial infections could be due to a ascending infection that comes through the biliary duct, blood borne (portal or arterial), direct inoculation in a wound, from another organ, anatomic structure, migration from peritoneal cavity

Jaundice

• Symptom NOT a disease

• Caused by hyperbilirubinemia

  • bilirubin is a result of the break down of RBCs which happens in the liver, spleen, and bone marrow

• Removal of bilirubin in the blood stream only occurs in the LIVER

• Yellowing of skin and other mucosa (sclera)

Prehepatic

• caused by processes that trigger excessive production/inadequate removal of bilirubin

  • production > removal

  • Unconjugated bilirubin (no chance for the liver to remove)

• No liver disease

• Hemolysis (excessive production) #1 cause

• hematoma (excessive production)

• Gilbert’s disease - autosomal disorder of hepatic bilirubin conjugation

  • inadequate removal

Hepatic

• Triggered by diseases that damage the liver

• Diseases cause necrosis or destruction of parenchymal tissue, so we get high bilirubin leaking into the blood stream

  • Viral Hepatitis

  • Alcoholic Liver disease

  • Drug induced liver disease

  • Chronic hepatitis due to various causes

  • Cirrhosis

• Mixed conjugated and unconjugated bilirubin (Mixed Jaundice)

  • Damage to liver impairs the ability to remove it (unconjugated) since we still have some function (conjugated)

  • May not pre proportional

Posthepatic (Obstructive)

• Trigger by disturbances of secretion of bilirubin in bile

• Since the bilirubin has already gone through the liver → its conjugated

• Gallstones in common bile duct

• Carcinoma in head of pancreas

• Carcinoma of the common bile duct

• Carcinoma of the gallbladder

  • (Late symptom)

Hepatitis (inflammation of the liver)

• Acute Viral hepatitis

  • Common Causes → A, B, C, D, E

    • hepatotrophic viruses are most common (this is what we are talking about)

  • Rare Causes → EBV, CMV, HSV, Viruses causing childhood diseases, Yellow fever virus

  • Clinically symptoms and severity depends on virus type

  • All forms of have the potential to become a unrecoverable disease and trigger death of liver

    • some forms are more likely

  • Jaundice (mixed), fever, nausea

  • Occur suddenly and can be intense to the point of no return → acute liver failure

  • A tends to resolve without issues

    • Could result in liver failure but not usually

  • B and C are more likely progress to chronic hepatitis in some cases

    • C also increases the risk of cirrhosis and liver cancer in the future

      • on the rise in baby boomers because the damage is insidious

Cirrhosis

• Cirrhosis is just end stage liver disease, results in loss of regular structure and function, leads to fibrosis (liver doesn’t regenerate THAT fast)

• Causes (alcohol and hepatotrophic viruses make up 65%, idopathic 30%)

  • Alcohol

    • 10-20 years of alcohol abuse

    • Major cause

  • Hepatitis B, C, D

    • Major cause

    • 10 years

  • Hereditary Metabolic Disease

    • Wilson’s disease

    • Hemochromatosis

    • Alpha 1 Antitrypsin Disease

  • Autoimmune

    • Primary biliary Cirrhosis

    • Primary sclerosing cholangitis

    • Autoimmune hepatitis

  • Biliary obstruction

  • Drugs

  • Cryptogenic (unknown causes)

• Clinical features of cirrhosis (Underlines are those from portal hypertension)

  • Coma

  • Facial Telangiectasia

  • Fector hepaticus

  • Muscle wasting

  • Liver large or small

  • Ascites

  • Thin hair

  • Jaundice

  • Parotid gland enlargement

  • Splenomegaly

  • Collateral veins (caput medusae)

  • Absent or reduced pubic hair

  • pupura

  • edema

  • Hemorrhoids

• Distant and Systemic Complications

  • Bleeding Tendency due to reduced clotting factors and thrombocytopenia

    • no clotting factors bb girl

  • Hematemsis and exsanguination from bleeding esophageal varices

    • These are very fragile, and when they break its end of life stuff

  • Hyperestrinism (estrogen is not metabolized so it stays high)

    • Spider nevi

    • Palmar erythema

    • Gynecomastia

    • small testes

  • Hepatic Encephalopathy

    • high ammonia consequence

    • Change in brain function → AMS

  • Hepatorenal Syndrome

    • Hypoperfusion of kidneys triggers Na+ retention which pumps up blood volume/pressure and which makes it more likely that kidneys will fail

• Labs

  • elevated ALT and AST (serum transaminases) show liver cell injury

    • ratio is supposed to be 2:1

    • elevated shows RECENT cell death

    • used to track progression of liver disease, at some point it may drop fast because you have no cells left

      • high to low shows a complete loss of functional tissues

  • Prolonged PT (prothrombin time), Hypoalbuminemia show loss of liver cell function

    • Prolonged PT (bleeding tendency because you take longer to clot)

    • No albumin or clotting factors

  • Blood ammonia level elevation shows loss of detoxification function

Alcoholic Liver Disease

• Alcohol is the most important cause of liver disease

• Fatty Liver

  • fatty streaking in the liver can occur after a single night of heavy drinking, however, its reversible (days to weeks)

    • If you keep repeating it, we can heal

    • 10-15% progress to alcoholic hepatitis

• Alcoholic hepatitis

  • Histologically you see fatty changes, focal necrosis, leukocyte infiltration, bile stasis

  • More severe than fatty liver

  • fever, leukocytosis, jaundice (mixed), abdominal pain

  • May progress to cirrhosis

• Alcoholic Cirrhosis

  • can be a progression of alcoholic hepatitis or its own thing (spontaneously)

  • The most serious complication of alcohol abuse

  • reasoning as to why some alcoholics get it and some don’t are unclear

  • May be able to be reversed it y’all stop dranking (FOREVER)

  • Liver is shrunk, firm, and nodular

Portal Hypertension

• Anastomoses formed in Portal hypertension

  • Portal circulation normally is low pressure and doesn’t normally connect with the systemic

  • Anastomoses (previously closed) get open with the pressures increase and we bypass the liver

    • Prevent rupture

  • Nutrients and metabolites are not metabolized correctly

    • like ammonia isn’t converted to urea

• Complications

  • Ascites (fluid in abdominal cavity)

    • Reduced production of albumin - hypoalbuminemia, reduced osmotic pressure of the plasma

    • Portal hypertension - increased transudation of fluid into the albumin, increases the hydrostatic pressure

    • Hyperaldosteronism - sodium and water retention in the kidneys (hypervolemic conditions)

  • Splenomegaly (big spleen)

  • Anastomoses between portal and systemic circulation open up

    • Hemorrhoids

    • Esophageal varicies

    • Caput Medusae - distended and enlarge umbilical veins

Drug Induce Liver Injury

• More likely to be a metabolite of the compounds metabolized by the liver

• Predictable (dose related) → sterotypical response (Tylenol, tetracycline)

  • necrosis

  • fatty change (tetracycline)

• unpredictable (occur at any time, at any dose, without warning) (sensitized or susceptible population) SCARY BOO!

  • viral hepatitis-like

    • haluthane

  • cholestasis

    • cloripromezine

  • chronic hepatitis-like

    • methyl dopamine (parkinsons)

  • granulomas

    • phenylbutasomes

  • tumors

    • oral contraceptives

Hereditary

• Anything that affects metabolism, affects the liver

• Gilbert’s syndrome - benign recurrent jaundice with unconjugated bilirubin

  • autosomal recessive disorder affecting bilirubin metabolism (UGT enzyme)

• Hemochromatosis - excessive accumulation of iron in many organs → cirrhosis

  • ferritan is saturated so you form hemosiderin which accumulates in the liver cells

  • treated with blood letting (leech time bb) (it’s just blood donating 🙂 )

• Wilson’s disease - excessive accumulation of copper (liver, eye, CNS) → cirrhosis

  • Autosomal recessive

  • Unknown mechanism, may be due to the liver not being able to excrete copper in bile

• Alpha 1 - antitrypsin deficiency - accumulation of AAT cirrhosis

  • Autosomal recessive resulting in the synthesis of an abnormal variant of alpha 1 antitrypsin which is synthesized in the liver, the defect means it can’t released.

  • It acculumates as cytoplasmic lobules in the liver → jaundice, hepatitis like symptoms and eventually cirrhosis

  • leading cause of childhood cirrhosis

Immune

• Autoimmune hepatitis

  • Chronic form of hepatitis

  • typically occurs in young women

  • Associated with other autoimmune disease (antibodies in serum ANA, ASM)

    • SLE, sarcoidosis

• Primary biliary cirrhosis

  • Characterized by destruction of intrahepatic bile ducts which then progresses to cirrhosis

  • Thought to be a type IV response (T cells)

  • occurs in middle-aged women

  • Chronic jaundice

  • Hypercholsterolemia, Antibodies in serum (AMA (anti-mitochondrial antibodies))

• Primary sclerosing cholangitis

  • Characterized by the destruction of extra and intrahepatic bile ducts

  • occurs in men younger than 40 yrs

  • associated with ulcerative colitis (60% of patients)

  • No specific antibodies

Gallstones (Cholelithiasis)

• formed from chemicals that are normally present in bile, just in excessive amounts

• common in US 20% of individuals over 65

• 3x higher in women

• Genetic predisposition is a major factor

  • higher incidence in whites

  • high incidence in populations with metabolic disorders (Pima Natives)

Cholesterol Stones

• Yellow (white)

• 75% of stones in the US

• Bile is supersaturated with cholesterol, deficient in bile salts

  • Causes the cholesterol to precipitate

• Increased by obesity, type 2 DM, use of statins and oral contraceptive

• tend to be smooth

Pigmentary Stones (bilirubin)

• black (the ones Dr. Elzie said she would make jewelry out of)

  • more common in US

  • Seen in individuals with chronic hemolytic anemia, cirrhosis

    • Cause the bile to have hella bilirubin

• brown stones

  • more common in the far East

  • Associated with biliary infections or infestation with biliary fluke

• Typically multiple

• tend to be rough and angular → more irritation

Complications

• Most gallstones are asymtomatic and require no treatment

• Only symptomatic in 20% of individuals

  • Triggers cholesistitis

  • block cystic duct

  • block bile duct

• Complications include pancreatitis, ulceration, infection, post hepatic jaundice

Tumors

• Primary or secondary

• Primary have a wide variety

• Secondary are more common

  • can reach liver through portal and arterial systems

  • Commonly from GI system, lungs, breast

  • multiple metastasizes

  • Metastatic tumor of the liver - round nodular with central area of necrosis (kinda like a granuloma)

    • liver tenderness, jaundice, splenomegaly, ascites

Benign tumors

• limited clinical significance

• Cavernous Hemangiomas

  • small

  • no symptoms

  • found in autopsy (5% of individual)

• Hepatocellular adenoma

  • most common in females

  • 90% in oral contraceptives

    • rare in other individuals

  • Highly vascularized

Malignant Tumors

• Hepatocellular carcinoma

  • most important malignancy

  • Highly malignant

  • 5X more common in men

  • most of these tumors originate with peeps with cirrhosis, Hep B/C, hemachromatosis, alpha 1 antitrypsin deficiency

  • Perineoplastic syndrome

    • hypoglycermia

    • hyperestroginism

    • erythrocytosis

• Cholangiocellular carcinoma of the liver

  • Bile duct tumor

  • rare in US

  • Poor prognosis

    • intrahepatic

      • very few symptoms early on

    • extrahepatic

      • result in jaundice early so better detection

• Gallbladder carcinoma

  • occurs in older

  • 2x females

  • native americans, mexicans have highest incidence in US

Male Repro

Infertility

• Can be caused by congenital defects, infections, tumors, trauma, or endocrine issues

Cryptorchidism

• Bottom line straight up the one or more of the testes do NOT descend into the scrotum

• 3 types

  • Abdominal (15%) → True

  • Inguinal canal (25%)

  • High Scrotal (60%)

• Inguinal canal and scrotal often lumped together and are known as “incomplete”

• These patients have and increased risk of testicular cancer

  • even with surgical correction

• Often times goes undetected in newborns

  • if undetected after 5 years → Orchiectomy is the only option and the patient will be infertile

    • Still fertile if it is only one testes

• Can be retractile and descend and then retract all the way to high scrotal/inguinal region

Infections

E. Coli

• Cystitis (in the bladder)

  • unlikely in men, unless they’re old (catheters increase risk)

• Prostatitis

  • 30-60 year old men

  • Doesn’t need to be infectious can be inflammatory

  • related to the stagnation of urine

  • Presents as pain during urination, urgency, fever, and tends to be recurrent

Gonorrhea and Chlamydia

• Epididymitis

  • point tender on palpitation

  • usually a complications of cystitis or prostatitis in older men

    • or urinary obstruction or prostatic surgery

  • in younger men think STI

• Urethritis

  • In men, you’re thinking STIs until proven otherwise

  • Mostly chlamydia and mycoplasma

• Gonorrhea presents with purulent discharge and inflammation

  • discharge, dysuria, urinary urgency/frequency

  • PMNs in exudate

• You always treat gonorrhea and chlamydia like they’re both there

  • 500 mg penicillin or ceftriaxone/1 Gm azithromycin/tetracycline, etc.

• Highly infections but there’s a high cure rate, treat it on the spot!

Mumps

• Classic orchitis

  • IRL its pretty muddy

Balanitis

• HSV 2 → vessicles

  • rain drop on a red petals

  • shallow, painful ulcers

  • tends to recur

  • Not curable

• Syphilis → ulcers

  • in the primary stage: painless chancre, inguinal lymphadenopathy

    • easy to treat here (DOXY) but often goes unreported due to mildness of symptoms

  • Secondary stage: macular rash, condyloma latum, hepatitis, other internal organ inflammation (pancreatitis)

    • Can occur 2 months to 2 years later

    • Treat with long-acting PEN G IM for 3 weeks

    • Condyloma latum tend to appear on palms and soles

  • Tertiary stage: characterized by CNS and cardiovascular lesions

    • occurs 2 to 20 years later

  • Syphilis is also called “the great imitator”

  • Diagnosis is based on antibody dection

• HPV → condyloma acuminatum (genital warts)

Mycoplasma (Mgem)

• bacteria infections of the epithelial mucus

• resistant to azithromycin

• VERY high correlation to “risky” sex behaviors

Tumors

• Male breast cancer tends to be a carcinoma in the BRCSA2 gene mutation

Rule of 90s

• 90% of these tumors affect men between 25-45

• 90% of these tumors are of germ cell origin

• 90% of these tumors are malignant

• 90% of patients survive for 5 years

  • Easy to find via self or provider exam

  • Angiogenesis is difficult for the tumor, so removal is easy

  • High capture rate

Germ Cell Tumors (most common)

• Tend to be found in physical exams

• Painless, heaviness noted in scrotum, maybe so vomiting and nausea

• Seminoma

  • less agressive than NSGCT

  • Serum marker: Beta hCG

• Nonseminoatous Germ Cell tumor (NSGCT)

  • Embryonal carcinoma

  • Teratocarcinoma

  • Choriocarcinoma

  • Mixed

  • Serum markers: alpha-fetoprotein and hCG

Sex Cord Tumors of the Testes

• May be a palpable mass near the epididymis

• Etiology may be increased endogenous testosterone (no steroids) with a normal endocrine workup

• 100% survival rate

• Leydig Cell tumor

  • Characterized by a painless mass, gynecomastia, ED, infertility

  • Most likely to cause pre-mature puberty

• Sertoli Cell tumor

  • Characterized by painless mass, breast tenderness

  • Treated with orchiectomy, lymphectomy, radiation, chemo not overly effective

Secondary Tumors

• Tend to metastases of lymphoma, carcinoma of prostate, kidney, large intestine

Carcinoma of the PENIS

• Rare in the US

  • More common in South Africa

• Tumors are squamous cell carcinomas

• Metastases occur first to inguinal lymph nodes

• Prognosis depends on the stage of the tumor

• Etiology → HPV

Diseases of the Prostate

Benign Prostatic Hyperplasia (BPH)

• Characterized by growth of the prostate which can lead to nocturia, urinary urgency/frequency, recurrent UTIs due to incomplete voiding, hematuria, urinary incontinence

• Periurethral hyperplasia can lead to bladder obstruction

• Most common cause of prostate cancer in middle aged men

• Treated with alpha-5-reductase inhibitors

  • halts the growth

• Prostatitis is common

• Rule out prostate cancer in the diagnosis

Carcinoma of the Prostate

• Most common cancer of internal organs in males (225,000 cases per year)

  • due to increase ability to detect, genetic, and environmental factors

• Tumor of old age (most commonly)

  • 85% of men that died were older than 65

  • Probability increases with age

  • young men can get it though

• 2nd leading cause of cancer death in the US and UK

• Annual incidence doesn’t match autopsy prevalence

  • there’s more than we think

• Idiopathic but multifactoral

• No Overt major risk factors

  • remains unsolved

• Hormonal influences appear to play a role

• African American men have a disproportionally high risk and their cancer is more likely to be aggressive

  • European (whites) in second, then East Asian

• Screening is controversial can be detected early using PSA scores (blood) but the next step is biopsy which is invasive and may not be clinically relevant

  • A high PSA score is anything above 4.0 ng/ml

• Tumor is most often located in the peripheral parts of the prostate

• Metastasizes to local lymph nodes and vertebrae, other bones, and internal organs

  • Bone metastases can be osteoblastic nature

Urinary

Developmental Diseases*

Renal Agenesis

• Can be unilateral or bilateral

  • If bilateral, this is not compatible with life and will result in a stillbirth

    • kidneys make amniotic fluid, so in bilateral renal agenesis there’s no fluid

• One or more kidneys just doesn’t form at all

Horseshoe Kidney

• Kidney tissue joins and get stuck under the inferior mesenteric artery

• Theres no migration of the kidneys to where they’re supposed to be, they stay in the pelvis

• Patients are prone to infections, stones, and damage

Multi-cystic Renal Dysplasia

• Can be unilateral or bilateral

  • unilateral has the best prognosis

  • In bilateral, you may have very little renal function or none at all

    • not super compatible with life

Polycystic Kidney Disease

• A result of genetic issues and abnormal chromosomes

• Always bilateral in nature

• Autosomal Dominant Polycystic Kidney Disease

  • Adult onset

  • Cysts develop over time

  • Cysts usually start appearing @ ~20 Years old

  • By 40-60 y/o cyst grow rapidly

• Autosomal recessive

  • You’re born with it (infantile onset)

Immune Mediated Glomerular Diseases*

• All are mediated by type III hypersensitivity → antibody-antigen complexes are deposited where they aren’t supposed to be

• Chronic renal failure can result with chronic glomerulonephritis

• Progression of these can lead to End-stage glomerulopathy (ESRD)

  • “chronic glomerulonephritis”

  • Numerous cases with the same result → terminally insufficient kidneys

Acute Renal failure

• Typically caused by Cresenteric glomerulonephritis

• Decrease GFR, Increase blood BUN and Creatine

• Destruction occurs in minutes to hours

Nephritic Syndrome*

• Acute glomerulonephritis associated with Lupus

• Damage mediated by inflammation

  • epithelial cells and basement membrane are damaged

• Another reason we treat strep and impetigo

• Clinical features

  • Hematuria

  • RBC casts and/or fragmented RBCs in urinary sediment

  • Oliguria

  • Proteinuria (<3.5 g/day)

    • non-nephrotic range

  • Generalized edema

  • HTN

Nephrotic Syndrome*

• Associated with lipid nephrosis (kids), membranous nephropathy, focal segmental glomerulosclerosis (adults)

• Damage to podocytes are mediated by noninflammatory measures

• Clinical features

  • Proteinuria (>3.5 g/day)

  • Hypoalbuminemia

    • leads to generalized edema and hyperlipidema

      • Since there’s no albumin the liver kicks in to make more but it also makes cholesterol

  • Lipiduria with lipid cast in urinary sediments

  • increased infections due to loss of Igs

  • Increased blood clot risk

Diseases that result in isolated hematoruria and proteinuria

• Berger’s (IgA disease)

• SLE

Metabolic Disease

Diabetic Nephropathy

• Glomerulopathy

• Tubular atrophy

Urinary Stones

Female Repro

Breast