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136 Cards in this Set

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Factors Affecting GFR
GFR = K [(Pc + p i) - (Pi + p c)]
GFR = 12.5 [( 60 + 0 ) - (18 + 32)]
GFR = 125 ml/min
Affected by: changes in filtration pressure changes in K (permeability)
Factors Affecting GFR
Changes in renal blood flow
Changes in afferent arteriolar diameter
Changes in efferent arteriolar diameter
Changes in perfusion pressure
Contraction of glomerular mesangial cells
Why do we need such a high GFR?
Wastes are generally filtered and not secreted
Wastes are in low concentration in the blood
General strategy: filter almost everything into the tubule then reabsorb only the wanted substances.
Reabsorption of Nutrients
Glucose, amino acids, vitamins, small proteins
Actively transported by carrier proteins or by endocytosis
Reabsorption nearly completed in the proximal tubule
Glucose Transport
Saturable
Tmax is approximately 320 mg/min
Threshold is approx 180-220 mg/min
Coupled to Na+ reabsorption
Located only in proximal tubule
Glucose Filtered Load
Filtered load (mg/min) = serum [ ] (mg/ml) X GFR (ml/min)
Estimating GFR
Plasma Clearance = Vol urine X [ ] urine
Hormonal Regulation of UO
Aldosterone
Antidiuretic Hormone
Angiotensin II
Atrial Natriuretic Peptide
Assessment of Kidney Function
Pain:
irritative symptoms: UTI
CVA tenderness: pyelonephritis
renal colic: nephrolithiasis
Labs:
Urine: dipstick, urinalysis, C&S, 24 hour
Serum: BUN (10-20 mg/dl), creatinine (0.5-1.5 mg/dl)
Urinalysis
pH (acidic)
protein (neg)
glucose (neg)
ketones (neg)
RBC < 5 cells per HPF
nitrites (neg)
leukocyte esterase (neg)
leukocytes < 5 cells per HPF
casts (neg)
Differential Dx of Hematuria
Cystitis
Neoplasm
Stones
Glomerulonephritis (RBC casts)
Differential Dx of Proteinuria
>150 mg/24h is significant
Functional proteinuria
Idiopathic and intermittent
orthostatic
glomerulonephritis
nephrosis: > 3.5 g/24h
Serum BUN and Creatinine
Expect increase in Cr of 1 to 1.5 mg/dl per day in acute renal failure
Ratio of BUN to Cr may help predict prerenal hypovolemia if >20:1
Follow Cr in chronic renal failure as an indicator of GFR
Renal Disorders
Obstructive
Infective (UTI, pyelonephritis)
Inflammatory (glomerulonephritis)
Chronic Renal Failure
Acute Renal Failure
Congenital Disorders
Horseshoe kidney
Supernumerary kidney
Renal agenesis
Polycystic Kidney Disease
Obstructive Disorders
Benign Prostatic Hyperplasia
Prostate Cancer
Bladder Tumors
Nephrolithiasis
Plugged Urinary Catheter
Urinary Tract Infection (UTI)
Etiology: ascending infection, E. coli
Risks: female, urine stasis, high pH
Manifestations
Lower UTI: irritative symptoms
urine + for nitrites and leukocyte esterase
cloudy, foul smelling urine
Upper (pyelonephritis): CVA tenderness,
WBC casts, fever, nausea and vomiting
Treatment: antibiotics
Glomerulonephritis
Etiology: Immune mediated damage to basement membrane
post-streptococcal, autoimmune
Risks: genetics, strep pharyngitis
Manifestations:
decreased GFR
leaky basement membrane
Treatment: steroids, chemo, supportive
“nephrotic”
leaky basement membrane
hematuria
proteinuria
“nephritic”
clogged tubules
decreased GFR
- oliguria
- edema
- hypertension
- azotemia
pyelonephritis
cause: infection
s/s: fever cva tenderness
prognosis is good
treatment is antibiotics
glomerulonephritis
cause is inflammation
symptoms are decreased gfr
prognosis is not good
treatment is antinflammatory
Nephrotic Syndrome
Ongoing Leaky Basement Membrane
proteinuria > 3.5 g in 24 hours
hypoalbuminemia
generalized edema
hyperlipidemia
Usually self-limiting
Chronic Renal Failure
Who is at risk?
glomerulonephritis
diabetic nephropathy
pyelonephritis
polycystic kidney disease
nephrotoxic exposure
obstructive nephropathy
75% nephron loss
Decreased renal reserve
no signs or symptoms
BUN, creatinine normal
may not be diagnosed
75% to 90% loss
Renal Insufficiency
polyuria, nocturia
slight increase in BUN, creatinine
may be diet controlled
>90% nephron loss
End-stage failure
uremia
Management of CRF
Restrict: fluids, Na+, K+, PO4
Low protein diet
Phosphate binding antacids
Vitamin D supplementation
Dialysis
Renal Transplant
Acute Renal Failure (ARF)
Sudden severe decrease in renal function
Prerenal
Intrarenal
Postrenal
Manifestations: Rapidly progressing uremia (50% mortality)
Causes of Prerenal ARF
Inadequate Bloodflow to Kidney
shock
trauma
sepsis
hemorrhage
dehydration
Causes of Intrarenal &Postrenal
Intrarenal: nephrotoxins
Postrenal: obstruction
BPH
stones
Differential Dx of ARF
Pre-renal oliguria:
history and signs of ECV depletion
low urinary sodium <10 mEq/L
high urine osmolality >500mosm/L
fractional sodium excretion < 1%
urine sodium over plasma sodium over urin cr over serum cr
Differential Dx of ARF
ATN (intrarenal, postrenal, prerenal)
lower urine osmolality (<350 mOsm)
urine sodium > 40 mEq/L
fractional sodium excretion >1.5%
tubular cell casts, protein in urine
Management of ARF
PREVENTION:
assess for adequate renal perfusion
avoid nephrotoxins (some antibiotics)
early treatment of obstruction
TREATMENT:
acute dialysis
fluid management
URINE FORMATION
FILTRATION
FLUID, IONS, NUTRIENTS, WASTES FROM GLOMERULAR CAPILLARY BLOOD INTO BOWMAN’S CAPSULE
i.e. from BODY towards URINE
note: large proteins and all blood cells are too big to be filtered.
URINE FORMATION
REABSORPTION
MOVEMENT OF WATER AND IONS, AND METABOLITES (glucose, amino acids, vitamins, proteins) FROM NEPHRON TUBULES BACK INTO BLOOD (PERITUBULAR CAPILLARIES)
i.e. from URINE towards BODY
mostly occurs in proximal convoluted tubule
URINE FORMATION
SECRETION
TRANSPORT OF H+, NH4+, CREATININE, DRUGS, TOXINS, K+ , ORGANIC SUBSTRATES FROM TUBULAR EPITHELIAL CELLS INTO NEPHRON TUBES
i.e. from BODY towards URINE
FACTORS AFFECTING URINE FORMATION
GLOMERULAR FILTRATION RATE
Hydrostatic pressure in glomerular capillaries (favors filtration) (~50 mmHg)
Hydrostatic pressure in Bowman’s capsule (opposes filtration) (~15 mmHg)
Net Hydrostatic Pressure ~35 mmHg
Colloid osmotic pressure in glomerular capillaries (opposes filtration) (~25 mmHg)
Colloid osmotic pressure in capsule is negligable unless damage has occurred
CHANGE OF BLOOD PRESSURE THUS AFFECTS GFR
AUTOREGULATION OF BLOOD FLOW TO KIDNEY (JG CELLS)
HORMONAL REGULATION : RENIN AND ANGIOTENSIN II, LATER ADH AND ALDOSTERONE
SYMPATHETIC NERVOUS SYSTEM PROMOTES GENERALIZED VASOCONSTRICTION (EXCEPT TO HEART, BRAIN, MUSCLES)
ABNORMAL CONSTITUENTS OF URINE
GLUCOSE
Glycosuria
if active transport mechanisms for tubular reabsorption are exceeded, glucose is found in urine.
only occurs if carbohydrate intake is excessive that normal mechanisms can’t clear it, or in pathologic condritions such as diabetes mellitus.
Albumin
in urine
Albumin
Albuminuria
most abundant blood protein, affects osmotic pressure of blood
should not pass through glomerular filtration membrane, but excessive exertion, pregnancy, overabundant protein intake may change permeability (physiologyical albuminuria).
Pathological: kidney trauma, heavy metal ingestion, bacterial toxins, glomerulonephritis, hypertension.
Ketone Bodies in urine
intermediate products of fat metabolism
expected during starvation
pathological: diabetes mellitus if also find glycosuria
may cause acidosis
Red Blood Cells = Hematuria
too large to pass through glomerular pores normally = pathology
kidney stones causing irritation and frank bleeding, physical trauma to urinary organs
may also be accidental contamination of urine by menstrual flow
Hemoglobin = hemoglobinuria
result of fragmentation of red blood cells (hemolysis), liberating hemoglobin into plasma, which then appears in kidney filtrate.
pathological: hemolytic anemia, transfusion reaction, burns, renal disease
Bile pigments = bilirubinuria
liver pathology like cirrhosis or hepatitis
White blood cells = pyuria
inflammatory process in urinary tract
Casts = hardened cell fragments
white blood cell casts, red blood cell casts (different forms of nephritis)
fatty casts (severe renal damage)
DISEASES AFFECTING URINE FORMATION
Diabetes Mellitus
Diabetes Insipidus
Pathological conditions causing abnormal constituents in urine mentioned on previous slides.
Myenteric Plexus
GI tract activity increases when stimulated
Tonic contraction of the intestinal wall inc.
Rhythmic contractions inc. in intensity
Rhythmic contractions inc. in rate
Velocity of conduction of excitatory waves along instestinal wall inc.
Excitatory fibers are cholinergic; inhibitory are purine-based NT such as ATP
Small Intestine
2-4 hours to traverse
Segmental contractions to mix
Peristaltic waves to move forward
Large Intestine
Slow progression at 5-10 cm per hour
Segmental contractions produce haustra
1-3 mass movements per day
Parietal Cells
HCL
Intrinsic Factor
Chief Cells
Pepsinogen
Surface epithelia and mucous cells
HCO3- and mucus
Secretions from Pancreas
HCO3-, Proteases, Lipases, Amylases
Secretion from Gallbladder
Bile acids, pigment, phospholipid
Secretions from intestinal epithelia
Brush border enzymes
Brush Border Enzymes
lactase
lactose glucose, galactose
brush border enzyme sucrase
sucrose fructose, glucose
brush border dextrinase
cleaves amylose branch points
brush border glucoamylase
maltose glucoses
Digestion and Absorption of Proteins
Pepsin: 15% of peptide bonds broken
Pancreatic proteases
Trypsin
Chymotrypsin
Carboxypeptidases
Brush Border
Peptidases cleave into 1 to 4 aa chains
Digestion and Absorption of Fat
Bile salts are amphipathic molecules that break up large fat globs into droplet
Lipase are water soluble - only work at surface of droplet
Triglycerides --------> FFA and glycerol
Bile forms micelles with FFA to keep soluble.
FFA are lipid soluble so absorb directly
Reabsorption of Bile
Bile is reabsorbed at terminal ileum
Passive diffusion and active transport
Transported to liver via portal blood
ALL reabsorbed bile is taken up on first pass by liver
Entire bile pool circulates 2 to 5 times per meal. 5-10% lost per day in stool
GI Disorders
Rank 3rd in total economic burden
60-70 million Americans have digestive disease
Many could be prevented or minimized by proper nutrition and changes in health practices
Dysphagia – difficulty in swallowing
1. Neuromuscular: pharynx – problem in delivery of bolus of food or fluid due to neuromuscular incoordination
2. Peristaltic activity is altered: Stricture or tumor: Progressive solid food dysphagia
Achalasia: esophageal motility disorder, loss of peristalsis in lower 2/3 plus impaired LES relaxation – food feels “stuck”
3. Problems with bolus entry into stomach – esophageal tumors (scleroderma), obstructions at LES
Mallory-Weiss syndrome: mucosal tears at distal esophagus, bleeding, pain – often caused by excessive vomiting
Odynophasia – pain in swallowing
Esophageal Diverticulum
Outpouching of the esophageal wall caused by weakness of the muscularis layer
Tends to retain food „³ leads to reports of gurgling, belching, coughing, and foul-smelling breath.
Trapped food causes esophagitis and ulcerations
Condition often progressive and may require surgery to correct defect
Oropharyngeal
Nasal regurgitation
Airway obstruction with eating
Coughing when swallowing
Immediate regurgitation
Hoarse voice
Esophageal
No airway distress
Late regurgitation
Chest pain @ meals
Frequent heartburn
Presence of collagen disease
Presence of Left supraclavicular node
Gastroesophageal Reflux Disease
Backward movement of gastric contents into the esophagus „³ leads to heartburn
GERD „³most common dis in GI tract
Relaxation of LES is by vagus n.
Pain sometimes confused with angina
Persistent reflux leads to Barrett¡¦s esophagus ¡V squamous muscosa is replaced by columnar epithelium found in stomach or intestines.
Increases risk of esophageal cancer
Esophageal Cancer
6% of all GI cancers
More common in over 50 – m/f = 2:1
Squamous cell - <50% - associated with dietary and environmental influences, ie., alcohol and tobacco use
Adenocarcinomas – often arise from Barrett’s esophagus - >50% and appears to be increasing
Located in distal esophagus and may invade the stomach
Endoscopy used to detect
Prognosis is poor b/c often metastasized before diagnosis
Disorders of the Stomach
Gastric Mucosal Barrier - Stomach is protected by tight cellular junctions, a protective mucus layer, and prostaglandins that serve to protect by improving blood flow, inc. bicarb secretion and enhancing mucus production.
Gastric irritation caused by
Aspirin and NSAIDS – damage ep cells, dec mucus prod, and inhibit prostaglandin synth
and Heliobacter pylori – thrives in acid environment, disrupts mucosal barrier that protects stomach from digestive enzymes
Gastritis - Inflammation of gastric mucosa
Acute – caused by local irritants like
bacterial endotoxins – like staph – abrupt and violent onset, vomiting
Caffeine, Alcohol, and Aspirin
Chronic Gastritis
Autoimmune - least common; antibodies to parietal cells and intrinsic factor; leads to hypochlorhydria, high intragastric pH and hypergastrinemia
- Associated with Hashimoto’s thyroiditis and Addision’s disease
- can also lead to pernicious anemia – deficiency of intrinsic factor leads to malabsorption of vitamin B12
Multifocal atrophic – most frequent in whites; unknown etiology
- reduced gastric acid secretion
- 2-4% develop gastric carcinoma
Chronic Gastritis
H. pylori ¡V most common ¡V these are small, curved, gram- rods that colonize mucus secreting epithelial cells (doesn¡¦t colonize other parts of GI tract)
- have multiple flagella which allows them to travel through mucus layer
How do they survive this environment? ¡V secrete urease (NH3+) to buffer
Can cause peptic ulcer „³ linked to development of gastric adenocarcinoma
Chronic Gastritis
Chemical gastropathy
Reflux of alkaline duodenal contents, pancreatic secretions and bile into the stomach
Seen in pts. who have had gastroduodenostomy and gastrojejunostomy surgery
Peptic Ulcer Disease - PUD
Group of ulcerative diseases that occur in upper GI tract – stomach and duodenum – areas exposed to acid-pepsin secretions
Approx 10% will or have experienced PUD
Associated with remissions and exacerbation
Duodenal ulcers 5X more likely than gastric
Duodenal seen at any age – most likely in early adulthood.
Gastric – affect older; peak 55-70
M/F ratio 3-4/1
Peptic Ulcer Disease - PUD
May affect one or all layers of stomach and duodenum
Can penetrate outer wall
Healing of muscularis layer involves scar tissue; but mucosal layers may regenerate
Often not perfect – leading to exacerbations
Peptic Ulcer Disease - PUD
Since 1980’s – shift in thinking about cause
Most cases are H. pylori infection followed by NSAID and aspirin use
not so much due to genetic predisposition, stress or dietary indiscretions.
All duodenal ulcers and 70% of gastric ulcers have H.pylori
Cramplike pain is rhythmic and frequently occurs when stomach is empty – during the night
Where’s the pain?
Pain often alleviated by food and/or antacids
Dyspepsia
Present with heartburn, indigestion, epigastric distress
Up to 2/3 will have no identifiable cause
One-half will have relief from placebo
Symptom profile does not differentiate between GERD, PUD, and non-ulcer dyspepsia (functional)
Physical exam is rarely helpful
Differential Diagnosis of gastro
NSAID: suspect PUD and treat
Helicobacter pylori: urea breath test or biopsy during endoscopy
GERD: Trial of H2 antagonists therapy
Functional: may improve with agents that increase motility
Zollinger-Ellison syndrome: rare; caused by gastrinoma – gastrin secreting tumor; found mostly in pancreas – check gastrin level
PUD with H. pylori
H. pylori is nearly always a factor in non-NSAID peptic ulcer disease
Conventional therapy with H2 blockers or H+ pump inhibitors has a 75-80% one-year recurrence rate
Treatment for H. pylori reduced recurrence rate to less than 5%
Cancer of the Stomach
7th most frequent cause in US
22,400 Americans got it, 12,100 died
Major cause of cancer death worldwide
Factors include genetic predisposition, carcinogenic factors in diet (N-nitroso and benzyopyrene found in smoked and preserved foods), autoimmune gastritis, gastric adenomas or polyps.
Increased 4X since 1930s – why?
Often asymptomatic until late
Surgery is treatment of choice.
Irritable Bowel Syndrome
Used to describe a functional GI disorder characterized by a variable combination of chronic and recurrent intestinal symptoms not explained by structural or biochemical abnormalities.
Hallmark is abdominal pain alleviated by defacation
Thought to be dysregulation of intestinal motor and sensory functions by CNS
Symptoms inc during stress
May have hormonal component as women notice exacerbations during premenstrual period and onset of disorder can occur during menarche.
Motility Diarrhea: IBS
Irritable bowel syndrome is a chronic (>3months) functional disorder with no identifiable pathology
Fluctuations in stool frequency and consistency (no nocturnal diarrhea)
Perceived abd distention, bloating, pain
Often associated with anxiety or depression
IBS
It is not IBS if fever, bloody stools, nocturnal diarrhea, or weight loss are present
Consider checking CBC, sed rate, albumin, and stool for occult blood to rule out inflammatory disease, consider lactose-free trial.
RX: restrict caffeine, gas producing food, high fiber. Rx depression
Inflammatory Bowel Disease
Ulcerative Colitis
Involves only the colon and rectum (usually start of inflammation)
Begins most often b/t 20-25
Mucosal layer is affected
Hallmark is bloody diarrhea and lower abdominal cramps – 30-40 BM/day
Associated with increased cancer risk after 8-10 years of disease
Inflammation tends to be continuous
Mild chronic, chronic intermittent, and acute fulminating
Crohn Disease
Recurrent granulomatous inflammation with skip lesions
Surface of bowel has “cobblestone” appearance
Mostly in submucosal layer - relatively sparing of smooth muscle layers
Intermittent bouts of fever, diarrhea, and RLQ pain, mass, and/or tenderness
Absorptive areas of intestine may be disrupted
Complications include fistula (tubelike) formation, perforation, abdominal abscess formation, intestinal obstruction
Can affect any portion of GI tract
30% are small bowel only
50% are small and large bowel
15-20% are large bowel only
Bowel Obstruction
Presentation
Pain, distention, vomiting, obstipation
Evaluation
Flat and upright abdominal film
Small bowel: less urgent
intestinal tube, decompression
Large bowel: urgent, danger of cecal perf
immediate surgical consult
Diverticulosis
Etiology:
Mucosal layer of colon herniates through muscularis layer
May be multiple diverticula
Common in western society 5-10% of pop older than 45, 80% older than 85
Almost non-existent in African and underdeveloped nations – Why?
Possibly diet (lack of fiber), dec physical activity, poor bowel habits, and aging
Diverticulitis
Etiology:
Microperforation with peridiverticular inflammation
Presentation:
Elderly with LLQ pain, severe constipation, nausea, fever
Evaluation:
CBC, abd film, CT if peritoneal signs
Rx: NPO, antibiotics, IV fluids
Appendicitis
Etiology:
Obstruction by fecalith (hard stool), twisting, inflammation
Presentation:
RLQ pain (classic, but may be anywhere), N&V, fever, diarrhea, RLQ tenderness
Evaluation: CBC, abdominal ultrasound
RX: immediate surgical consult
Diarrhea
Affects 500 million children throughout the world and leading cause of death children under 4
About 220,000 american children hospitalized for gastroenteritis
Two-types
Large-volume
Small-volume
Chronic Diarrhea: Stool Studies
Stool Osmolality: normal gap < 50
Laxative screen: Mg, PO4, SO4
Fecal leukocytes: Inflammatory disease
Ova and parasites: Giardia, cryptosporidium
Fecal Fat analysis: > 10 g/24 hrs indicates malabsorption
Fecal weight: > 1000 g is secretory
Malabsorption syndrome
Syndrome implies a common constellation of symptoms arising from multiple causes.
Ex. Celiac sprue, Crohn’s disease, and resection
Celiac sprue – rare chronic disease, mucosal lesion of small intestine and impaired nutrient absorption
Lose absorptive villi
Improves when gluten is removed from diet – maybe immunologic response
Colorectal Cancer
2nd leading cause of death in US.
105,500 cases, 57,100 died
80% of pts are over 50
Inc with family history, Crohn’s, UC and adenomatous polyps (most common neoplasm of intestine), perhaps diet
Aspirin may protect
May be asymptomatic for a long time
Bleeding often first symptom
Liver
Liver is largest visceral organ – about 3 lbs.
Liver is surrounded by Glisson’s capsule
Liver has dual blood supply
Hepatic artery brings 300 mls/min
Portal vein brings 1050 mls/min
Liver stores about 450 mls of blood – can be shifted back to circulation when needed
50-100,000 lobules in liver
Metabolic Functions of Liver
CHO, Protein and Lipid Metabolism ¡V also builds CHO from proteins, converts sugars to fat for storage
CHO metabolism ¡V stores excess glucose as glycogen, converts galactase„³fructose„³glu,
Protein synthesis ¡V albumin, fibrinogen, clotting factors
Contains aminotransferases necessary for transamination
Oxidative deamination removes amino group from aa
NH3+ is generated (toxic to cells, especially neurons) so converted to urea in liver and excreted by the kidneys
Drug and Hormone Metabolism
Metabolizes lipid-soluble substances that can’t be excreted by kidneys
Phase 1 – chemical modification or inactivation of a drug
Phase 2 – conversion of lipid-soluble substances to water-soluble derivatives
Called biotransformation
Hormone inactivation – insulin and glucagon (proteolised or deaminated), T3 and T4 (deiodinated), steroid hormones (biotransformed)
Bile Production and Cholestasis
Liver secretes about 600-1200 ml/day
Bile functions in the digestion and absorption of fats and fat-soluble vitamins from the intestine, helps excrete bilirubin, excess cholesterol and metabolic end-products that can’t be eliminated in the urine
Approx 94% of bile salts are reabsorbed into portal circulation and recycled to liver
Bile salts travel this circuit about 18x before being excreted – called enterohepatic circulation
Cholestasis
Decrease in bile flow
Results in bilirubin, cholesterol and bile acids accumulating in blood
May be caused by intrinsic liver disease – intrahepatic cholestasis;
Or by obstruction of large bile ducts – extrahepatic cholestasis
Bile accumulates in canaliculi and hepatocytes
Diff Dx: Jaundice - icterus
Jaundice occurs with bilirubin level > 3 mg/dl (normal 0.2-1.2)
Increased RBC breakdown
Impaired liver uptake of bilirubin
Dec conjugation of bilirubin
Impaired excretion of bilirubin
Indirect bilirubin
Unconjugated

Elevated with increased RBC breakdown or impaired liver uptake
Bound by albumin so no urine bilirubin
Direct bilirubin
Conjugated- soluble in bile
Elevated with impaired excretion of bilirubin from liver
Water soluble, so is found in urine
Diff Dx: High Indirect Bilirubin
Hemolytic process, hematoma
Gilbert’s syndrome: genetic impairment of bilirubin uptake by liver -benign
Crigler-Najjar syndrome: genetic deficiency of enzyme for conjugation
Liver bypass: portocaval shunt, cirrhotic shunt
Diff Dx: High Direct Bilirubin
Hepatocellular injury:
hepatitis
drugs
hemochromatosis
Alpha-1 antitrypsin deficiency
Cholestasis:
stones, tumors, strictures
cholangitis
Acute Hepatitis
Etiology: acute liver inflammation and cellular injury: viral, toxic
Three phases: prodromal or preicterus period, icterus, and convolescent period
Presentation: jaundice, anorexia, fatigue, diffuse abd discomfort, dark urine
Evaluation: History of viral or toxin exposure, AST, ALT, Alk phos, bilirubin, serology for viral hepatitis
Hepatitis A
Formerly called infectious hepatitis
Caused by small, unenveloped RNA containing HAV
Brief incubation-15-45 days; usually transmitted by fecal-oral route.
Virus replicates in liver, excreted in bile, and sheds in stool (stopped by IgM inc)
Often occurs in epidemics
Drinking contaminated milk or water, or eating shellfish from infected waters
Children are often asymptomatic so help spread
Hep A vaccines are available
Hepatitis B
CDC estimates 200-300,000 new cases each year and 1.25 million chronic carriers
Endemic in regions of Africa and SE Asia
Caused by HBV – double stranded DNA v.
Complete virion, called Dane particle, has outer envelope and inner core with HBV
Longer incubation, more serious, transmitted through infected blood or serum. Antigen can be found in most secretions so can spread by oral or sexual contact.
Three antigens associated with virus
Hep B vaccine recommended for all children and pregnant women routinely tested
Hepatitis C
Single stranded RNA v
At least 6 genotypes and multiple subtypes
How does this affect pathogenicity, immune mechanisms, and antiviral medications?
Most common cause of chronic hepatitis, cirrhosis, and hepatocellular cancer
Contaminated blood transfusions use to be most common route – now 1:103,000
Injecting drug use now highest risk factor, along with tattooing, acupuncture, body piercing
Incubation 15-150 days (ave. 50)
Children often asymptomatic, jaundice uncommon
Persistent v. that leads to chronic diseases
Hepatitis D
Hepatitis Delta Virus - defective RNA virus
Two forms
Coinfection with acute Hep B
Super-infection which Hep D is imposed on chronic Hep B
HDV can inc severity of HBV
Transmission similar to HBV
No direct treatment for Hep D but since it is tied to Hep B – prevent and treat Hep B
Acute Toxic Hepatitis
Etiology: exposure to hepatotoxin or its metabolite
Evaluation: No definitive tests:
history of exposure is important
negative viral serology screen
improvement after discontinuing drug
if alcohol is the toxin, AST > ALT, 2:1
Chronic Alcoholic Liver Disease
Etiology: chronic, heavy ETOH exposure
Only 15-20% of alcoholics develop liver disease
Men > 4-6 drinks/day, Women > 3-4/day
Pathogenesis: unknown
Presentation:
fatty liver – steatosis; becomes enlarged
Hepatitis – common in “spree” drinkers
cirrhosis
Alcoholic-induced Liver Disease
Causes 200,000 deaths annually
5th leading cause
Estimated 10 million alcoholics in US but only 10-15% get cirrhosis
What does this suggest?

Death associated with liver failure, bleeding esophageal varices, and kidney failure
Cirrhosis of the Liver
Fibrotic liver – early stages called micronodular or Laennec cirrhosis
loss of hepatocellular functions
obstruction to bloodflow from the gut
Etiology
Chronic alcohol use (most common)
Biliary (obstruction in bile drainage)
Postnecrotic (viral, toxic hepatitis)
Cardiac (right heart failure, liver congestion)
Functions of the Liver
Nutrient metabolism (glucose, protein, fat, fat soluble vitamins)
Production of serum proteins and enzymes (albumin, clotting factors etc.)
Detoxification of hormones, drugs
Bile synthesis (conjugation of bilirubin)
Urea synthesis
Manifestations of Liver Dysfunction
Impaired protein synthesis
bleeding (clotting factor deficiency)
edema (hypoproteinemia)
immune deficiency (substrate for antibody)
Accumulation of toxins and hormones
feminization (excess estrogens)
poor metabolism of drugs
spider nevi (estrogen)
Manifestations of Liver Dysfunction
Inadequate bile synthesis
increased bilirubin level
jaundice
Inadequate urea synthesis
increased blood ammonia level (NH3)
hepatic encephalopathy
Release of marker enzymes into blood
AST (SGOT)
ALT (SGPT)
Occult GI Bleeding
Detected by FOBT: worry colorectal CA
Indicated for iron deficiency anemia in males or postmenopausal females
Unless S&S suggest Upper GI etiology (heartburn, dyspepsia PUD) start with colonoscopy (or barium enema)
If no source, follow with endoscopy
Acute Abdominal Pain
Tension: spasm, associated with intense peristalsis (irritant, infection, obstruction)
Ischemia: intense constant pain (bowel strangulation, volvulus adhesion)
Inflammation: first localized to serosa covering inflamed part then extends to abdominal wall causing reflex muscle spasms (rigidity, involuntary guarding
Localization of Abdominal Pain
Stomach, duodenum: mid epigastric
Small bowel: periumbilical
Colon: low abdomen, midline
Rectum: sacrum and perineum
Gallbladder: mid epigastric radiates to RUQ or right scapula
Pancreas: mid epigastric radiate to back
Appendix: RLQ, but variable
Cholecystitis
Etiology:
95% associated with stone in cystic duct
Presentation:
Often obese female, fever, RUQ pain with scapular or epigastric pain, colicky, N&V
Evaluation:
CBC, RUQ ultrasound, HIDA scan
RX: Prompt cholecystectomy
Acute Pancreatitis
Etiology: unknown
Associated with ETOH, biliary disease
Presentation:
Severe epigastric and back pain
Evaluation:
CBC, glucose, calcium, electrolytes, amylase, lipase (renal studies)
Severity index
pancreatitis scale initially
Initially
Age over 55
WBC > 16,000
Blood glucose > 200
Base deficit > 4
Serum LDH >350
AST > 250
pancreatitis scale first 48 hours
During first 48 hours
HCT drop of >10%
BUN rise >5 mg/dl
PaO2 < 60
Calcium < 8 mg/dl
Fluid sequestration of > 6 liters
Diff Dx: Steatorrhea
Pancreatic steatorrhea:
> 90% of exocrine function lost
Bile salt deficiency:
decreased ileal reabsorption (Crohn)
blocked secretion (cholestasis)
Bacterial overgrowth syndromes:
stasis of small bowel contents
Mucosal defects: Celiac disease (sprue)
esophagitis
reflux (GERD) - pain after meals
- “heartburn”
gastritis
ASA, ETOH - epigastric pain
H. pylori
Crohn's regional enteritis
? Etiology - diarrhea with
blood and mucus
ulcerative colitis
? Etiology - bloody diarrhea
diverticulits
low fiber diet low abdominal
pain, fever
appendicitis
obstruction - RLQ pain, fever
“fecalith” - rebound pain
peritonitis
perforation - severe pain, ileus
bowel ischemia - guarding, rigid
pancreatitis
biliary disease - pain to back, shock
ETOH - high lipase, amylase
cholecystitis
cholelithiasis - RUQ pain
- steatorrhea
hepatitis
viral, acute ETOH - jaundice, big liver
- high AST, ALT
- flu-like symptoms