Hepatobiliary and Pancreatic Flashcards
1
Q
Amino acid changes in PSS?
A
Increased aromatic: tyrosine, phenylalanine
Decreased branched chain: leucine, isoleucine, valine
2
Q
MicroRNAs in hepatic disease?
A
Chronic hepatitis - miR-126/122/29a. 122 corr with fibrosis. Increase ET1 too
miR-200 hepatocell carc
mrR21/122 mucocoele
mrR122 gen hepatic dz (
3
Q
Dermatological presentation of hepatic disease?
A
Superficial necrolytic dermatitis
4
Q
Compounds associated with hepatic encephalopathy?
A
Increased: ammonia, aromatic AAs, endogenous benzodiazepines, gamma-aminobutyric acid (GABA), glutamine, phenol. short chain FAs, tryptophan, false NTs
Decreased: alpha-ketoglutarate
5
Q
What is the half life of ALT, ALP and AST in dogs and cats?
A
ALT: 48-60/6
AST: 22h/77m (nb 20 % in mitochondria)
ALP: 70/6
6
Q
What links ALP to cell membranes? Why is it released in cholestasis?
A
Glucosyl phosphatidyl inositol linkage
Cholestasis - bile acids detergent, increased glucosylphosphatidylinositol phospholipase activity
7
Q
When is GGT increased?
A
Zone 1 peri portal disease
8
Q
When do steroids start increasing ALP?
A
mRNA 24-48h, expression gene 10d
9
Q
Mechanism of RBC changes in hepatobiliary disease?
A
Microcytosis - impaired iron transport
Target cells/poikilocytes - altered RBC cell membrane lipoprotein content/deformability
Anaemia - chronic dz, haemorrhage
Thrombocytopenia - sequestration, decreased thrombopoietin
10
Q
Why do dogs have bilirubin in urine?
A
Can conjugate it renal - have enzymes - esp males, plus low renal threshold
11
Q
Mechanism of ammonium biurate stones?
A
No uric acid conversion to allantoin (uricase)
12
Q
Low USG?
A
Loss medullary hypertonicity, decreased cortisol metabolism, psychogenic
13
Q
Glucose?
A
Decrease when 75 % liver gone - decreased glycogen stores, gluconeogenesis, insulin clearance and glucagon response
14
Q
Increase in globulin?
A
Decreased filtration and clearance of toxins and bacteria
15
Q
How is ammonia incorporated into the urea cycle?
A
Carbamoyl phosphate synthesise 1 (helped with nacetylglutamate)
16
Q
What is more sens/spec - single BA, fasting NH3, pre and post BA PSS?
A
Sens - pre + post BA then ammonia then single BA
Spec - ammonia > BA
17
Q
Urine versus serum BAs?
A
Increased specificity lower sens HEPATOBILIARY
Equivalent serum in cats
Lower sens PSS
18
Q
Values of ammonia for PSS?
A
> 45 - 98/89 % sens/spec
Don’t do tolerance test if > 150 basal
19
Q
What clotting factor does the liver not produce?
A
vonWB subtype of VII
20
Q
Protein C?
A
Binds protein S to degrade V and VIII clotting factors
Decreased in PSS vs PVH
21
Q
What is used to conjugate bile acids?
A
Glycine/taurine
22
Q
Bile salt hepatocyte export and import?
A
Bile salt export pump (multi drug resistance associated protein 2)
Sodium dependent taurochlorate cotransporter
Ileum - apical sodium bile acid cotransporter
23
Q
What transports bilirubin and bile acids in blood?
A
Organic ion transporting polypeptide
24
Q
Top end normal CBD cat/dog?
A
< 4 <3
25
Sensitivity of AUS for PSS? CT?
80 - 100 epss, 100 IPSS
Portal vein:aorta < 0.8 v sensitive, < 0.65 - PSS
CT - 96 sens 89 spec - 5.5 x more likely than AUS
26
AUS with MAPSS? Sensitivity?
Left dorsal renal, 60 %, splenorenal
27
Contrast enhanced hepatic ultrasonography?
Decreased perfusion in malignant
| Increased enhancement benign lesions esp late phase
28
MRI more sens PSS than CT?
No - less - but more specific
29
Incidence of haemorrhage after tru cut bx?
Cat - probably around half major haemorrhage but not corr with coags
30
Stains for liver?
Rubeanic acid/rhodanine - copper
Sudan - lipid
PAS - glycogen
Masson's trichrome/sirius red fibrosis
31
Utility of FNA for liver disease?
Highest sens vac change and neoplasia (50 % each)
32
Tru cut liver?
NB vagotonic shock with autofire
Discordant with wedge half the time (better if neoplasia)
Increased concordance 14 G - more portal triads
33
Goals of therapy in liver dz?
Address underlying cause
Decrease or prevent inflammation, oxidative damage, fibrosis and copper accumulation
Provide nutrition
Manage complications
34
Major bile acids?
Chenodeoxycholic acid and cholic acid from cholesterol hydroxylation form trihydroxy bile acid taurocholate
35
Mechanism of action SAM-e
Synthesis of glutathione via homocysteine transmethylation and transsulfuration pathway
Prevent hepatic glutathione depletion
Modulate apoptosis, anti-inflammatory, anti carcinogenic, improve membrane structure, fluidity and function
Inhibits pro-inflamm cytokine production, prevents development of oxidative stress, improved redox status
Increases hepatic GSH (and amount of reduced GSH), decrease oxidised glutathione disulphide form
Does not prevent vacuolar hepatopathy
Decrease level of hepatic enzymes and amount of tx delay when combined with silymarin in dogs tx lomustine
36
N-acetylcysteine?
Formation L-cysteine, precursor of glutathione
Stabilises glutathione conc, improves redox status
37
Silymarin?
Flavanoligans including silybin - most biologically active around 50 - 70 %
Antiox: free radical scavenger, decreased lipid per oxidation, suppress hydrogen peroxide/superoxide/lipoxygenase, increase glutathione
Anti-inflamm: decrease TNFalpha/IL1beta/NFkappabeta, inhibit kuppffer cells
Anti-fibrotic: decrease hepatic stellate cell activity and decrease hepatic collagen expression
Might be choleretic
Increase bioavailability if give with phosphatidylcholine
Amanita phalloides tox, lomustine
38
What enzyme conjugates bilirubin?
UDP glucuronosyltransferase
39
Vit E mechanism?
Alpha tocopherol most biologically active
Antioxidant: protect phospholipid from oxidant injury, scavenge free radicals, minimise lipid peroxidation
40
Ursodeoxycholic acid?
Hydrophilic bile acid - displace toxic hydrophobic ones from circulating pool. Increase fluidity of bile.
Choleretic (protonated UCDA absorbed by biliary epithelial cells and leaves bicarb - bicarb draws water)
Inhibit hepatocyte apoptosis
Decrease IL1/2, B lymph AB, (immunomodulatory)
Stabilise mitochondrial function
Increase glutathione (increase methionine adenosyl transferase activity to generate SAMe)
Anti-fibrotic - NAFKB
41
D-penicillamine?
Copper chelator and anti-fibrotic (prevents collagen molecule cross linking)
42
Zinc?
Increase metallothionein synthesis by enterocytes to bind copper
43
How to manage fibrosis in hepatic disease?
Caused by increase in stellate cell and fibroblast activity - steroids for latter, decrease ox injury for former as increases stellate cell activity
44
What precipitates hepatic encephalopathy?
Increased ammonia production in the GI tract:
Poor quality poorly digestible protein, or excess protein in diet - reaches colon for bacterial degradation
Constipation
GI haemorrhage
Azotaemia (increases systemic ammonia generation)
Blood transfusion of stored blood
Protein calorie deficiency and catabolism
Factors influencing the CNS uptake or metabolism of ammonia:
Alkalosis
Hypokalaemia
Hypoglycaemia (potentiates activity and production of neurotoxins)
Inflammation (cytokines are neurotoxic and potentiate ammonia)
Sedative and GA drugs
45
What effect does ammonia have in the CNS?
Inhibitory. Depletes glutamate and alters glutamate receptors, impairs mitochondrial function.
46
Taurine defiency?
Important in cats - conjugation of bile acids, take from muscle if depleted
NB neck ventroflexion!
47
Important amino acids in cats?
Taurine, arginine, methionine, cysteine
48
Cell cycle inhibitors in chronic hepatitis?
Increase p21, cell senescence, correlated with survival.
49
Evidence for immune mediated aetiology in chronic hepatitis?
Lymphocytic inflammation
MHC Class II haplotype association (ESS/Dobermann)
Positive serum autoABs, antihistone ABs (Doberman)
Familial association (Dob, lab, westie)
Assoc with other immune disorders (lab)
Female (dob, lab, ess, acs)
Response to immunosuppressives
50
Age CH in diff breeds?
Dalmatian, dobermann and ESS younger
Lab, ECS, Cairn older
ACS younger than ECS
51
Signalment for lobular dissecting hepatitis?
Younger
Standard poodle, ACS, rottie, GSD, Gret
80 % have ascites
52
Best screening test for CH?
Increased ALT more than 2 months
53
Indicators of portal hypertension?
GI/gall bladder/pancreatic oedema, decreased portal vein velocity, hepatofugal flow
Decreased protein C, PV:aorta <0.65, anaemia, microcytosis, increased ammonia and bile acids
54
Difference between chronic hepatitis and lobular dissecting hepatitis on histopath?
Minimal inflamm in latter
55
Cirrhosis
Fibrosis with nodules
56
Factors to consider when predicting bleeding risk in CH?
```
PT/aPTT 1.5 x upper RI
plt <50
PCV < 30
Fibrinogen < 100
vWF < 50 %
BMBT > 5min
```
57
Where should a sample for copper be collected from?
Least affected region
58
How many portal triads do you need to make dx?
12 - 15 (but sometimes don't need that many if v obvious widespread disease)
59
Evidence for immunosuppressive tx in CH?
Pred:
Increased length of survival time dobermans
Complete remission around 1/3
ESS - imp enzyme bili and survival
Labs increased survival cf historic controls with combo aza - MST 630 d
Ciclosporin:
Remission in 76 %
60
What to do if granulomatous inflammation on hepatic bx?
Search infectious dz
61
CH survival time?
Around 600 d
62
Negative CH px factors?
Ascites (not cockers) cirrhosis, lobular dissecting hepatitis, hypoglycaemia, hypoalphaglobulin, hyperbili, decreased plt, increased coags, fibrosis, necrosis, bridging/marked fibrosis, small liver, portal lymphadenopathy, SIRS, clinical score
63
How often is copper the cause of CH?
Around a third depending on breed (cupric oxidation state Cu2+ is hepatotoxic, gen O2 free radicals)
64
How might copper accumulate?
Increased diet, primary defect in metabolism, altered biliary excretion
Toxicity depends on concentration, molecular association and sub cellular localisation
65
Bedlington?
Copper metabolism gene MURR1 containing domain 1) - auto recessive
66
Labrador copper mutation?
ATP7B/A (copper excretor, COMMD1 acts on it) ALSO DOBERMAN ATP7B
ATP7B = ceruloplasmin - biliary excretion - Wilson's dz
NB COMMD1 NOT described in dobermans/lab
Cat - ATP7A/B
67
How often is copper accumulation detected in feline liver biopsies?
12 %, NB lower RI for cats
68
Major copper assoc CH breeds?
Bedlington, Dalmatian
Lab, doberman (female predip)
Westie, skye terrier
69
What is ATP7A?
Basolateral enterocyte copper transporter - upreg = more Cu absorb
70
What transports copper from the GI lumen?
Copper transporter 1
71
Stages of bedlington terrier copper disease?
Cu accum begins from 8-12w
Cu 400 - 1500, no clin/HP abn, poss Cu granules
Cu 1500 - 2000, HP inflamm
> 2000, clin signs
Could get haemolysis if copper released from hepatocytes
NB heterozygotes might start to accumulate copper then resolve at 15m
Huge amounts of copper > other breeds
72
Measurement of hepatic copper?
< 400 normal, > 2000 required for morph/func change and clin dz
Non copper CH, copper up to 1500
Take from least affected areas, might be falsely low in regenerative nodules or fibrotic areas
Atomic absorption spectrometry needs less liver than spectrophotometric
73
Copper hepatic histopath?
Centrilobular copper zone 3, adjacent and distant hepatocytes
Grading system (none solitary cells small groups large groups large areas diffuse) corr well with measurement - 3+
74
When to use diet for copper? Chelation? Zinc?
```
Diet:
> 600
Chelate:
D-penicillamine, if > 1500 overall or if > 750 plus centrilobular
Zinc:
no additional benefit cf diet?
```
If severe lymphocytic w/ less macrophages consider immunosupp
75
What collagen is increased in hepatic fibrosis?
I and III - cross linking
I - Masson's trichrome
III - reticulin
Stellate cells unregulated by endothelin from sinusoidal epithelial cells and PDGF/ROS/TGFbeta from macrophages, s endothelial cells and platelets
76
WSAVA classification of liver histopath in cats?
Acute/chronic neutrophilic cholangitis
Lymphocytic cholangitis
Destructive cholangitis
Chronic cholangitis assoc with liver fluke
77
What is lymphocytic portal hepatitis?
Poss aging change or secondary to extra hepatic dz - NO BILE DUCT INVOLVEMENT!
80 % of cats > 10
78
Most common bacteria in neutrophilic cholangitis?
E coli
Salmonella enterica, Klebsiella, Strep
Majority one species, more likely to culture from bile
Higher numbers of E coli on FISH cf lymphocytic. 25 % bacteria around bile ducts.
79
Number of IBD and pancreatitis in NC cases?
83% and 50 %
FISH pos pancreas?
80
Most consistently increased hepatic enzyme in feline liver disease?
AST
Bile acids more sensitive than any enzyme
81
Clotting factor changes in feline liver disease?
Decreased 7 and 13
82
Vitamin D in feline liver disease?
Decreased cholestatic liver disease, corr with WBC, most decreased in hepatic lipidosis, PTH higher
83
What distinguishes cholangitis from cholangiohepatitis
Extension of inflammatory cells beyond the limiting plate
84
Acute neutrophilic cholangitis versus chronic?
Minimal biliary hyperplasia and fibrosis
Bacteria may only be in larger bile ducts if very acute
Chronic - biliary hyperplasia, periductal sclerosing fibroplasia, bridging. fibrosis, bile duct rupture, bile leakage, necrosis, abscess
Can be non supp or mixed lymph/plas with variable neuts
85
What feline cholestatic liver disease is most likely to be associated with pancreatitis?
NC, but other studies have found equal
86
Chronicity feline cholestatic liver disease on imaging?
Hyperechoic periportal and tortuous bile ducts
87
What lymphocytes in feline LC?
Predominance of T cells
Is Helicobacter or bartonella involved?
Persians? Older than NC?
88
Most consistent LC clin path?
Globulins
Icterus, ascites, HE as advanced
Variable increased hepatic enzymes
89
LC histopath?
Small lymphocytes around bile ducts, mostly periportal, often portal fibrosis/bridging fibrosis
May infiltrate bile duct and hepatic parenchyma
May get plasma cells and eosinophils
Portal lipogranulomas, portal B cell aggregates
Maybe have less intense lymph if chronic mono lobular fibrosis
90
What embryonic veins form the portal vein?
Cranial and caudal mesenteric
80 % blood and 50 % O2 supply to the liver
91
What is the cause of intrahepatic PSS?
Abnormal vitelline venous system development
92
What is the difference between PVH with and without portal hypertension?
More severe or more diffuse intrahepatic vascular malformations?
93
Consequences of hepatic vascular malformations?
No trophic factors (insulin/glucagon) for hepatic growth
Poor hepatic development, deficient protein production reticuloendothelial dysfunction, altered fat/protein metabolism, hepatic atrophy and failure
94
Pathophys of hepatic encephalopathy?
Ammonia:
Increases brain tryptophan and glutamine - decreased ATP availability, increased excitability, increased glycolysis, oedema, decreased microsomal NaK ATPase
Tryptophan:
Direct neurotox, increased serotonin, inhibitory
Glutamine:
Altered blood brain barrier ammonia transport
SCFAs:
Decreased microsomal NaKATPase, uncouple oxphos, impair O2 utilisation, increase free tryptophan by displacing from albumin
Aromatic AAs:
Decrease DOPA neurotransmitter synthesis, altered neuroreceptors, increase false neurotransmitter synthesis
False NTs:
Tyrosine > octopamine > phenylalanine > methionine > mercaptans
Impair norepi action, synergism with ammonia and SCFA, decrease brain urea cycle, decrease ammonia detox, decrease microsomal NaK ATPase
Phenol:
From phenylalanine and tyrosine, decrease cell enzymes, neuro/hepatotox
GABA:
Inhibitory
Bile acids:
Membranocytolytic effects, alter membrane permeability, BBB more permeable to toxin, impaired cellular metabolism and cytotoxic
Endogenous benzodiazepines:
Neural inhibition, hyperpolarise neuronal membrane
Alpha ketoglutarate:
Goes down, this reduces ATP avail and less ammonia detox
95
Breed feline PSS?
DSH Persian siamese himalayan Burmese, males maybe overep
96
Inheritance of PVH?
Autosomal inherited Cairn
97
NCPH?
Doberman, rottie, cocker
98
Clinical signs and shunt morphology?
CNS signs most common with...?
Urinary signs most common with?
More caval than right azygous and more if insertion caudal to liver vs diaphragm
Most CNS splenocaval
Urinary right gastric (also older, male, hx medical management)
99
Older dog EHPSS?
Splenonephric and splenoazygous
100
Role of microcytic anaemia in PSS?
Defective iron transport, decreased TIBC/iron, increased Kupffer cell iron stores
Target cell dog poikilocyte cat
101
Difference NCPH vs PSS?
Former increased bilirubin
102
Clotting factor changes in PSS?
Decreased II, V, VII, X
103
Ascites and vascular malformation?
AEPSS
HAVM
NCPH
104
AUS sens/spec PSS?
74-95/67 - 100
105
How to distinguish intra from extra hepatic PSS on portovenography?
Portal vein divergence T13
106
Name some branched and aromatic amino acids
Aromatic - tyrosine, phenylalanine
| Branched - valine, leucine, isoleucine
107
Where are most HAVMs?
right/central, 25 % 2 lobes
108
When should you suspect insufficient ligation post PSS surg (bile acids)?
< 50 fine, > 94 pre/post to investigate
Protein C helpful too, coags helpful too
109
Hepatic function test diagnosis PSS
BA: postprandial up to 100 % sens, NB maltese
Ammonia: pre prand up to 88 %, post prand 6h 91 %, ammonia tolerance 95 - 100 % NB ornithine transcarbomylase deficiency
Protein C: < 70 % PSS not MVD
Hyaluronic acid: increased PSS, decreased with surg
110
Factors which would raise concern for development of postoperative PH?
Ascites, vomiting, pain, hypotension, DIC, shock
111
Problem with PSS and hypoglycaemia?
periop, 1/3 don't respond to dextrose
112
Incidence of PSS post op seizures?
12 % dogs, around half recovery
1/3 cats, half central blindness (transient)
113
Surgical versus medical management for shunts?
Medical - half pts with MST 9m, 1/3 long term survival MST 5y
88 % dead medical versus 22 % surg
More poor px IHPSS with medical
114
Histopath steroid hepatopathy?
Vacuolated cytoplasm and sometimes nucleus, glycogen, zone 3, generalised with chroniticty
115
UCCR in scottie glycogen vac hep?
UCCR normal 75 %. Adrenals enlarged 25 %. GBM 16 %
116
What lipoprotein is changes in feline hepatic lipidosis?
Increased LDL decreased HDL
117
Prognostic factors in feline hepatic lipidosis?
Negative - old, anaemic, secondary cause
| No assisted feeding
118
Acetominophen tox?
NAPQI (bioactivated by cp450 and detox by glutathione conjugation - acute centrilobular hepatic necrosis
Dose dependent
Cats - absence of VGTI16 and ABCG2 transport export
119
Phenobarbital tox?
Poss secondary bio activation/hepatotox other drugs as induce cp450?
Dose dependent, cumulative
Bridging portal fibrosis bile duct hyperplasia nodular degeneration.
Serum conc = risk factor
120
Azole antifungals?
N-deacetylketoconazole = tox metabolite, covalent bind liver protein, deplete glutathione
Fluconazole and decrease dose less tox
121
Azathioprine?
Oxidative metabolites, depletion antiox, gen by xanthine oxidase
GSD at risk?
122
Amiodarone?
MDSA ox metabolite, uncouple oxphos
123
Lomustine
Mech?
Median 4 dose and 350mg/m2 - cumulative
Boxers and young dogs
Portal haemosiderin Kupffer cells
124
Tetracycline?
Inh beta oxidation of FAs in mitochondria and inhibit lipoprotein secretion
125
Potentiated sulphonamide?
Idiosyncratic - nitroso metabolites, covalent protein binding, haptens
Hepatic necrosis
126
Caprofen
Always ALT increase, never ALP, idiosyncratic
Bridging necrosis
Lab
127
Methimazole
Ox metabolite Nmethylthiourea gen flavin monooxygenases, glutathione depletion
Centrilobular necrosiis
128
Diazepam?
> 5d use, centrilobular necrosis/biliary hyperplasia
129
What might impair phenobarbital clearance?
Felbamate
130
Amanita phalloides tox?
Inh RNA polymerase, decreased protein synthesis and necrosis of metabolically active cells, hepatic and renal tubular necrosis
Silybin decreases uptake by OATP1B3, prevents fatality
131
Blue green algae?
Microcystin and nodularin, inhibit serine/threonine protein phosphatase, hyperphosphorylation, cytoskeletal disruption
Hepatic necrosis, glutathione depletion
Cholestyramine might bind the toxins
Nodularin does renal tubular necrosis
132
Cycad palm
Seeds most tox but all parts of plant.
Cyasin bioact to methylazoxymethanol by gut bacteria
Cycad AAs neuro toi
Centrilobular necrosis and neut inflamm
133
Cholelithasis in dogs and cats?
Dogs - calcium rare are canine GB can absorb free calcium. Cholesterol/bilirubin
Cat - cholesterol, bilirubin, calcium
134
Risk factors for cholelithiasis?
increased hydrophobic cholesterol in bile, bile stasis, hypertrig/bili, endocrine dz, cholesterol transportation/absorption defects
135
Timing of biliary tree dilation in cholelithiasis?
GB 24h, extrahepatic bile ducts 24-48h, intrahepatic 5-7d
136
Common bacteria in canine cholangitis?
E coli, enterococcus, clostridium, bacteroides, strep
Bile culture pos 60 %
137
How well do cyto/culture agree with gall bladder aspirate?
Almost perfect if no AB, 85 % otherwise
138
Gall bladder abnormalities and culture?
Sensitive but not specific
139
Bacteria associated with emphysematous cholecystitis?
E coli, clostridium perfringens
140
Leptin?
Increased in GBM dogs
141
Causes of GBM?
Hyperplasia of mucus secreting glands and mucous accumulation
Impaired GB motility - accumulation of bile salts (stim mucous), DM/hT4/HAC decrease gall bladder emptying
Increased unconjugated bile acids - HAC, hydrophobic, epithelial injury and mucin secretion
Impaired relaxation sphincter of Oddi - hT4, impaired relaxation. Also altered cholesterol metabolism and. decreased bile secretion
Sheltie and imidacloprid
ABCB4 transporter mutation (phosphaditylcholine across canalicular membrane) - alter bile composition?
142
Bile acids and GBM?
Taurochenodeoxycholic acid and deoxycholic acid stim mucin secretion
Unconjugated chenodeoxycholic acid and deoxycholic acid increased in HAC
Taurocholic acid/taurodeoxycholic acid/taurochenodeoxycholic acid conjugated
2 primary bile acids = cholic acid and chenodeoxycholic acid
Secondary BAs (unconjugated) - deoxycholic acid, ursodeoxycholic acid, lithocolic acid
143
Positive culture in GB mucocoele cases?
9 - 66 %
Enterococcus, enterobacter, E coli, staph, strep
144
UCDA in GBM?
Might increase canalicular transporters which could be helpful in gene defect
Decreases mucin formation and decreases formation cholesterol crystals
145
Negative prognostic factors GBM?
Clinical for disease, increased ALT, hyperbili, decreased alb, phosphate, ALP, azotaemia , rupture
146
Best place to culture in GBM?
FISH GB wall most sens
147
Border terrier GBM?
Transglutaminase 21gA autoABs
148
Cobalamin half life in dogs?
6 - 12w
149
Components of cobalamin receptor in ileum?
Cubam, amnionleess
150
Where do GI bacteria produce cobalamin?
Colon - after receptors
151
Cobalamin biliary recycling?
Bile haptocorrin
152
Cobalamin storage?
Liver and kidney
153
Renal cobalamin handling?
Cobalamin reabsorbed by megalin PCT - cobalamin/transcobalamin II complex
Cubam - renal resorption of albumin, transferrin and vit D binding protein
154
Consequences of cobalamin deficiency?
Lack of methylmalonyl CoA mutase activity increases methylmalonic acid and decreased n-acetyl glutamate therefore decreased carbomyl phosphate synthetase activity
Lack of methionine synthase activity - decrease methionine, increase homocysteine, decrease tetrahydrofolate, increase 5 methyl tetra hydrofolate
Homocysteine - neurotox, hepatic degeneration and fibrosis, Heinz body anaemia
Methylmalonic acid - neuro, and ammonia neuro
CBC - anaemia neutropenia hyperseg neut megaloblastic
155
What might increase homocysteine or methylmalonic acid in the absence of cobalamin deficiency?
Renal cardiac disease, decreased alb, delayed serum separation
Renal insufficiency dehydration SIBO URINE - bacterial contamination
156
What is holotranscobalamin?
Cobalamin plus TCII - measured in humans
157
Immerslund grasbeck syndrome?
Hypoglycaemia, hyperammonaemia, ketoacidosis, oral lesions, anaemia, proteinuria (renal cubam for reabsorption)
158
Beagles and cobalamin?
Cubulin mutation
May get degenerative liver disease (hyperhomocystinaemia?)
Immunosupressed - ?decreased phagocytic activity
159
Border collie and cobalamin?
Cubulin, less severe beagle, delayed onset
160
Giant schnauzer and cobalamin?
Amnionless mutation (more like border collie than beagle)
161
Aussie shephard cobalamin?
Their own amnionless mutation (border collie more than beagle presentation)
162
Komondor cobalamin?
Autosomal recessive cubulin splice variant
163
Other causes of B12 deficiency
Hyperthyroidism (not functional), hAC, multi centric lymphoma, dysbiosis
NB Bacteroides can use cobalamin bound to intrinsic factor
164
What cobalamin supplementation is thought to be most effective?
Hydroxycobalamin
165
Risk factors for pancreatitis?
```
Hypertriglyceridemia
Maybe SPINK (contraversial) no CFTR or PRSSI
Endocrine - hAC hT4 DM
```
166
What is cathepsin B?
Activator of trypsinogen
167
Effect of feeding in pancreatitis?
Decreased hospitalisation time (may not decrease mortality?)
168
Does organophosphate toxicity cause pancreatitis?
In dogs but probably not cats (experimental)
169
Low fat feline pancreatitis?
Not necessary - they need arachidonic acid from omega 6 FAs
170
Mode of inheritance in EPI
Not simple auto recessive
171
Pathophys canine EPI
Atrophy - probably subclin immune med first - T lymph infiltration
172
Breeds?
GSD, rough collie, eurasian
chow, ckcs, whwt
173
Alternative EPI diagnosis?
Faecal pancreatic elastase 1 (resistant to GI absorb) - nb false pos
174
Why might bacterial overgrowth decrease fat absorption?
Deconjugate bile salts, decrease activity
175
Cobalamin and EPI?
Decreased survival if marked decrease
