Hepatobiliary/Pancreas Flashcards
Liver is responsible to produce
–Bile acids/salts = help absorb lipids and bilirubin
Bilirubin is considered
Waste from RBC’s after being destroyed by splenic macrophages
Liver Functions:
#3
- Metabolism
- Detoxification
- Synthesis of plasma proteins/cholesterol/coag factors
Fat Soluable Vitamins
K.E.D.A
– GI, Liver and Pancreas work intangent to absorb fat soluable vitamins and fat
–If any portion malfunctions → malabsorption occurs → eliminated thru stool
Liver Anatomy
–2 surfaces: diaphragmatic surface + Visceral surface
–Falciform ligament → attaches liver to diaphragm
–6 lobes LLat/Lmedial/Quadrate/Rmedial/RLat caudate lobes
Where is gallbladder located?
Between quadrate and R medial liver Lobes
Hepatic circulation
–Portal vein = 75-80% of blood supply
– Hepatic Artery 20-25% of supply
–Processes blood from GIT via Hepatic Portal vein
–Hepatic Artery (celiac artery branch) supplies blood to liver
–Ciruclation travels from peripheral lobules → interior → sinusoids → larger fenestrations of sinusoids in endothelial cells
–Blood from sinusoids leave each lobule via central vein and ultimately thru hepatic vein
Hepatocytes
–located inside sinusoids and come into contact w/ blood
–large pores allow large molecules (protiens etc) made by hepatocytes to enter blood circulation
Kupffer Cells
Macrophages in the liver that engulf foreign substances
Canaliculi
Bile Ductules located between each hepatocyte
–empty into large bile ductules → ultimately empty into bile duct @ triad → CBD empties directly into duodenum
Functions of Bile
#2
–necessary for lipid digestion intestines
–transport hemoglobin for excretion
Sphnicter of Oddi
Controls bile duct entrance into duoedenum
CCK’s role in gallbladder function
CCK released from duodenum mucosa → stimulates contraction of gallbladder or relaxation after fatty meals
Bilirubin Excretion Pathway
#6
–RBCs broken down via extravascular hemolysis
–removed via mononuclear phagocytic system in Liver/spleen/bone marrow/lungs/ lymph nodes
–Macrophages consumed RBCs causing them to rupture -> release hemoglobin via hemolysis
–Hb broken down into heme + globin
–Heme converted to Biliverdin (green pigment)
–Biliverdin converted to Free or Unconjugated bilirubin
Unconjugated vs conjugated Bilirubin
–Unconjugated: enters bloodstream → combines with albumin → goes to liver for absorption
–Conjugated : → released into bile and ultimately enters SI
–Fecal bacteria reduce bilirubin → urobilirubin to give feces/urine color
Carbohydrate breakdown process via Liver
Monosaccharides = glucose/fructose/galactose → glucose metabolized to produce ATP via Glycolysis
–Fructose/Galactose converted too glucose by liver for energy
Glycogen
Stored glucose in liver/skeletal muscles
–excess stored in fat
Glycogenolysis
Process to break down glycogen into glucose monomers for glucose use in post absorptive state (between meals)
Gluconeogenesis
Synthesis of Glucose from NONcarb sources → to provide glucose when levels decline
–utilizes pyruvate (from AA breakdown of proteins), lactate, glycerol
Triglycerides
Lipids used for energy when glucose not readily available
–Glycerol created and converted into glucose via Glyconeogenesis
Fatty Acid Metabolism
FA end up as Ketones with excessive FA metabolization
–overwhelms oxidative capability of Liver to convert FA to energy
–Too many ketones build up if not used
Protein Production via Liver
Liver responsible for nearly all plasma protein synthesis
–Alb and clotting proteins
–Converts AA into ketoacids → used by liver for energy production or glucose/FA
–Degraded AA = ammonia = converted by hepatocytes to Urea→ excreted by kidneys
Glucose/Na+ Diffusion gradient
–Glucose reliant on gradient created by Na+ for intracellular movement
–Glucose w/i enterocyte = unfavorable gradient and prevents glucose entering enterocyte
–Na+/K+ pump in enterocyte x3 Na+ OUT and x2 K+ ions IN → lowers Na+ gradient inside cell
– creates gradient that favors Na+ movement from GIT into enterocyte
–Na+ moves into cell = glucose moves by Co-transport w/ Na+
Pancreatic Endocrine functions
#2
Islets = secrete different hormones
– Beta cells = insulin
–Alpha cells = glucagon (increase BG via glucogenesis)
– delta cells = somatostatin inhibits the secretion of insulin and glucagon, as well as GH, and diminishes the activity of the GIT
Pancreatic Exocrine functions
#3
Acini groups = release secretions into lumen → duodenum
–Lipase = breaks down lipids into FFA and monoglycerides
– Proteases = breaks down proteins into AA
– Amylase = breaks down starches into maltose
What stimulates Pancreatic cell receptors?
#3
Acetylcholine
CCK
Secretin
Relation between Intestinal digestion and Pancreatic enzymes
Intestinal phase of digestion has neural and endocrine stimulus to increase pancrease secretions
EPI
Exocrine pancreatic Insufficiency
–Results from diminshed/reduced production of exocrine proteolytic enzymes
–Pancreatic atrophy/chronic pancreatitis
Role of CCK with pancreatic proenzymes
CCK stimulates duodenal mucosal cells to serete enteropeptidase in duodenal lumen -> enteropeptidase activates trypsinogen to trypsin -> activates other proenzymes release by pancreas
Cholecytitis types
What can cause it? #4
- Neutrophilic
- Lymphoplasmacytic, follicular
caused by infection/duct obstruction/trauma/systemic dz
Clin Path of Cholecystitis
Consistent with hepatobiliary dz
– elevated ALT/AST/AlkPhos/GGT
–Tbili/cholesterol
Inflammatory leukogram -> leukocytosis/Neutrophilia
Infection Agents with Cholecystitis
E.coli
Clostridium
–Can cause Emphysematous cholecystitis
Which breed is prone to bacterial Cholecystitis
Dachshunds
Choleliths composition
Calcium carbonate
bilirubin pigments
Gallbladder mucocele causes:
combination of mucin production/↓ GB motility
–dyslipidemias
–glycocorticoid excess
–hyperadrenocorticism
Hepatitis
inflammation cell infiltrates w/i hepatic parenchyma
Acute vs. Chronic hepatitis
Acute = combination of inflammation/hepatocellular apoptosis/necrosis
Chronic = presence of fibrosis with regenerative nodules + inflammatory infiltrate, apoptosis
Feline Cholangitis complex types
- Neutrophilic
- Lymphocytic
Neutrophilic Cholangitis in cats
what can this be associated with?
–Infiltration of neutrophils in intrahepatic bile ducts
– may be associated with IBD and pancreatitis in cats
Lymphocytic Cholangitis in cats
–Chronic form of dz with mixed inflammatory infiltrates
–small lymphoctyes/plasma cells
–bile duct hyperplasia
Role of Copper with Hepatitis
adverse efx of excess copper o
Causes/major mechanism for copper storage
–Excess hepatic chopper contributes to chronic hepatitis in dogs
–Related to excess dietary copper
–Biliary excretion major mechanism for maintaining copper homeostasis = any cause of cholestatsis = ↑ copper levels
–Excess copper damages hepatocytes by causing oxidative stress/cellular degeneration
Bedlington Terrier inherited defect with copper hepatic excretions
Infectious K9 Hepatits
–Adenovirus type 1
–rare due to vaccine - but young unvaccinated dogs at risk
–corneal edema/anterior uveitis seen
FIP
what causes it?
–caused by feline enteric coronavirus
–can affect any organ in the body
– lesions associated with neutrophil macrophages infiltration
–pyogranulomatous lesions noted on liver capsule
Leptospirosis common serovars
L. icterohaemorrhagiae
L. canicola
L. pomona
L. hardjo
L. grippotyphosia
Leptospirosis
CS seen
–acute renal failure +/- hepatic involvement
–pulmonary hemmorhage, uveitis, acute fever
–septicemia: bacterial seeding of liver 2nd to bacteremia via translocation
Lepto Treatment
Penicillin for leptospiremic stage
Doxycycline for carrier stage
Hepatic Failure
Acute = hepatocellular necrosis + fat accumulation, hepatocellular dropout
Chronic = hepatocellular necrosis but with fibrosis/inflammation/hyperplasia
Difference between Acute Liver failure and Acute Liver Injury
ALI = hepatocellular damage + necrosis but maintains function
ALF = has compromised function
Hepatic Encephalopathy
Compounds involved
Counsequences of HE
–Neurosynchiatric syndrome
–Typically occurs w/ more than 70% hepatic function lost
–Circulating compounds: ammonia/ aromatic AA/ endogenous benzos/ GABA/ Glutamine
– Impede neuronal/astrocyte function = cell swelling
–inhibits cell membrane pumps/ion channels
–elevation in intracellular Ca++
–Electrical activity depression
–Interference w/ oxidative metabolism
3 Classifications of HE
Acute
Bypass
Chronic
Toxic Affects of HE: Ammonia
#4
– Increases brain tryptophan/glutamine
– ↓ ATP availability
– ↑ excitability/glycolysis (causes sz)
–causes brain edema
Produced by GI flora; normally converted to Urea/Glutamine in Liver
Toxic affects of HE: Bile Acids
–affects/alters cell membrane permeability
– BBB more permeable to HE toxins;
impaired cellular metabolism
Toxic affects of HE: ↓ a-ketoglutaramate
Division from krebs cycle for ammonia detoxification; ↓ ATP availability
Toxic Affects of HE: Endogenous Benzodiazepine
Neural inhibition; hyperpolarize neuronal membrane
Toxic Affects of HE: False neurotransmitters
impairs norepi action ↓ ammonia detoxidication in brain urea cycle
Toxic Affects of HE: GABA
Neural inhibition; ↑BBB permeability
Toxic Affects of HE: Glutamine
Alters BBB AA transport
Toxic Affects of HE: Manganese
Elevated levels seen with Hepatic failure/encephalopathy
Toxic Affects of HE: Phenol
Synergistic w/ other toxins/ lowers cellular enzymes/ neurotoxic/hepatoxic
Toxic Affects of HE: Tryptophan
Directyly neurotoxic/ increases serotinin levels
Toxic Affects on Chronicity with HE
GABA and endogenous benzos surpass excitatory stimulus = coma/CNS depression
Toxic Affects of Acute Liver Failure
Can lead to cerebral edema
– elevated ICP
– +/- brain herniation
Metabolic derangements with HE
hypoglycemia
dehydration
hypoK+
Azotemia
Alkalemia
Coagulation disorders with HE
#8
–decrease in facor synthesis
–increase in factor utilization
–decrease in factor turnover
–increase in fibrinolysis/thromboplastin release
–Dsyfibrinogenemia
–decrease plt #s/Function
–Vit K deficiency
–Increase production of anticoagulants
Hypoglycemia see with HE
Liver crucial for body glucose regulation
–involved with glycogenesis, glycocenolysis, glycogen storage
–Euglycemia can still be maintained with 75% loss of liver parenchyma
–Once glycogen depleted → fat/muscle/body proteins used for ADP → creates negative nitrogen balance/decreased muscle mass
Sepsis with Liver Failure
–Liver Exposed to many types of pathogens via portal blood flow/GI venous drainage
– Inhibition of metabolic activity of granulocytic cells/cell adhesion/chemotaxis
–Reduced # of Kupgger cells = allows pathogens to translocate from portal circulation to systemic circulation
Pulmonary Edema with HE
–2nd to altered permeability of pulmonary capillaries
– result from hypoAlb, low colloid oncotic pressure and vasodilation
O2 Extraction with HE
Lower in HE pts from tissue hypoxia
–lactic acidosis
–further exacerbated by hypoxemia = worsens cerebral dsyfunction = accelerated cerebral hypotension and edema
Portal Hypertension with HE
2nd to Cirrohsis w/ chronic liver failure
–sinusoidal collapse blocks intrahepatic flow = increased protal pressure
–portal vein thrombosis
CBC findings with HE
#5
–Target cells, acanthocytes, anisocytosis
–non-regen anemia = chronic dz, GI bleeding, PSS
–Regen anemia = blood loss from ulceration
–Leukocytosis OR Leukopenia = infx causes or bacterial translocation
–Consumptive thrombocytopenia = infx or immune causes
Elevated ALT/AST
Leak from cells with cell membrane dysfunction
ALT value
More liver specific with short half life 24-60hrs
AST Value
Present in many Liver muscle RBCs
ALP value
Many catalysts → bone, liver, steriod induced (dog only)
–Activity increases with cholestatic dz
GGT value
Found in many tissues but biochemically measured ones located on membranes of hepatocyte canalicular cells and biliary epithelial cells
–useful for cholestatic dz diagnosis (more specific than ALP)
When is Icterus visible?
Tbili 2.3-3.3 mg/dl
What % of total proteins snythesized by liver
25%
–Albumin ONLY produced in liver
What % of cholesterol is synthetized by liver?
50%
–hypocholecterolemia seen with liver dz
UA sediment findings with Liver Failure
–Ammonium biurate crystals w/ protal systemic vascular anomalies
–Biliurbinemia seen with cats (dogs normally have small amount, cats DO NOT)
Respiratory affects from HE
#2
– Centrally induced hyperventilation/respiratory alkalosis → Renal excretion of K+ excretion = worsening hypoK+ = exacerbated HE
– Hypocapnia = shifts CO2 intracellularly to extracellularly = ↑ intracellular pH/accelerating use of phosphate to phosphorylase glucose = hypoPhos = RBC hemolysis
Diet managment for Hepatic Failure
Low aromatic amino acids (animal proteins)
–Milk/soy/vegetable proteins contain low AAA and high in branches chain AA
– Valine, Leucine, Isoleucine
Nutriceutical therapy for Hepatic Failure
#3
SAME = hepatoprotective, antioxidant, antiinflammatory
VIT E = antioxidant minimizes lipid peroxidation of hepatocyte
Milk Thistle = antioxidant and free radical scavenger, slows hepatic collagen formation
Liver Vascular Anatomy involved with Portal Hypertension
Portal vein = carries blood from GIT/gallbladder/pancreas/spleen TO liver
Portal venous Pressure
Ohm’s Law P = Q x R
PVP = portal blood flow x intraheptic resistance
Cause of Portal Hypertension
PH caused by ↑ resistance in portal
-pre, -intra - post hepatic circulation = ↑ portal blood flow
– ↑ resistance caused by hepatocyte damage = changes in hepatic architecture
→ fibrosis, microthrombi, regenerative nodules
Sinussoidal Endothelial Cells
–Normally produce vasoactive substances to regulate sinosoidal resistance - vasodilatory and vasoconstrictive substances
–Endothelial Dsyfunction = impaired sinussoidal relaxation 2nd to overproduction of vasoconstrictors
Hepatic Stellate cells
Store lipids and Vit A around sinusoids
–injury = HSCs to secrete inflammatory cytokine factors
Sheer stress
Sheer stress in splanic vessels with vasodilator release = splanic arterial dilation → compensatory hyperdynamic circulatory state (↑ Cardiac index and ↓ systemic arterial resistance)
RAAS effects with Portal Hypertension
– ↓ effect of circulating blood volume = RAAS/ADH activation
–Na+/H2O retention = ascites
– promotion of translocation of bacteria into portal system
Classifications of Portal Hypertension
Prehepatic
Intrahepatic
Posthepatic
Pre-hepatic Portal Hypertension
↑ resistance in extrahepatic portal vein
–result of intraluminal obstruction or extra compression
–Hepatic arteriovenous fistulas = PH due to arterial blood overloading portal venous system
– Congenital PSS
Intra-hepatic Portal Hypertension
#3
↑ resistance in hepatic microcirulation
–presinusoidal → resistance in terminal intrahepatic protal vein tributaries
– sinusoidal → result of fibrotic hepatopathies
– post sinusoidal →veno-occlusive dz from endothelial damage and hepatoytes (toxins/chemo agents)
Post-hepatic Portal Hypertension
Obstruction of larger hepatic veins
–post-hepatic vena cava or R atrium
– ↑ resistance in RA due to <3 failure/pericardial dz or pulmonary hypertension
Budd-Chiari syndrome
Budd-Chiari Syndrome
Obstruction of hepatic outflow in caudal vena cava or large extrahepatic veins
– tumor, thrombosis, congenital fibrous webs causing compression (intra-luminal or extra-luminal)
– vena cava stenosis
Diagnosis of Portal Hypertension
PVP via direct or indirect measurement
Direct = catheterization of protal vein, manometer or pressure transducer inserted
Indirect = angiographic balloon catheterization
CBC findings with Portal Hypertension
Microcytosis w/ acquired portosystemic collaterals
–mild thrombocytopenia
–anemia
Biochem findings with Portal Hypertension
Moderate - marked enzyme activity 2nd to necroinflammatory liver dz
–post-hepatic PH = mild - moderate elevated serum 2nd to hepatic necrosis or ischemia from congestion
–ammonia / total bile acids elevated with functional hepatic failure
–hyperbilirubinemia
– Intra-hepatic PH = ↓ Alb/Urea/Cholesterol
Coag Findings with Portal Hypertension
Upregulation of pro and anti - coagulant factors
–platelets activated by damaged endothelium
→ intra or extra hepatic clot formation
Peritoneal Fluid findings with Portal Hypertension
Protein content of ascites
– Pre-hepatic/pre sinusoidal = < 2.5 g/dl
Post-hepatic / sinusoidal = > 2.5g/dl
Ascites 2nd to Portal Hypertension
Imbalances of Starlings Law; ↑ hydrostatic PVP drives fluid into interstitial space
–vasodilation in splanchnic activates RAAS/SNS = volume expansion ↑ hydrostatic pressure in portal vasculature
HypoAlb 2nd to Portal Hypertension
Synthetic Dysfunction ↓ vascular colloid osmotic pressure = worsens ascites
