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1
Q

list 7 general functions of the liver and examples

A

1) metabolic conversions
2) secretory - bile
3) excretory - urea and uric acid
4) synthetic - globulin, albumin, prothrombin, clotting and anti-clotting factors
5) storage - lipid, glycogen (glucose)
6) detoxifies
7) filters blood - removes foreign particulate matter

2
Q

position of liver in terms of other organs, what plane sits in, what side sits and how held in position

A

positioned between the diaphragm cranially and the stomach and intestinal mass caudally
- It extends across the median plane
○ bulk lies to the right in all species
-held in position largely by the pressure of the viscera and by its close attachment to the diaphragm.

3
Q

what percentage of body weight is the liver in carnivores, omnivores and herbivores

A

○ 3-5% of body weight in carnivores
○ 2-3% in omnivores
○ 1-1.5% in herbivores.

4
Q

palpation for the liver in the dog

A

right side doesn’t go beyond costal arch so not palpable unless diseased
Left side does slightly extend beyond costal arch so could be palpable

5
Q

what encloses the liver beneath the serosa

A

the tunica fibrosa

6
Q

what are the two surfaces of the liver and what do they contact

A

1) Cranial (parietal) or diaphragmatic surface – convex and fits into the concavity of the diaphragm
2) Caudal or visceral surface - concave and in contact with the visceral organs - has portal area for portal vein etc

7
Q

what does the porta of the liver contain

A
  • the hepatic artery;
  • nerves and lymphatic vessels;
  • the portal vein
  • and the common bile duct.
  • also the Fossa of the gall bladder,
    containing the gall bladder, which lies between the quadrate and right medial lobes (dog).
8
Q

what are the two borders of the liver, where do they go and what is present in one of them

A

1) Dorsal border - Is extended further caudally and dorsally on the right side by the caudate process which carries a deep impression for the cranial pole of the right kidney.
Towards the median plane, the dorsal border carries a groove for the passage of the caudal vena cava (so goes through middle of liver) and to the left of this a notch for the oesophagus
2) Ventral border - sharp edged and continuous around the periphery of the organ, except dorsally.

9
Q

List the lobes in the dog

A

1) left lateral
2) left medial
3) quadrate
4) right medial
5) right lateral
6) caudate process
7) papillary process

10
Q

List 6 ligaments involved with the liver

A

1) coronary
2) falciform
3) right and left triangular
4) hepatorenal
5) round
6) lesser omentum

11
Q

what are the 3 ligaments that tether the liver to the diaphragm and where found

A

1) coronary ligament - laterally continuous from the triangular ligaments
2) facilform - fat-filled fold in the dog passes from abdominal wall to diaphragm and liver where disapears into the umbilical fissure
3) right and left triangular attach to tendinous region of the diaphragm

12
Q

hepatorenal ligament, round ligament and less omentum what connect and what is important about the round ligament

A

hepatorenal - caudate process to the ventral surface of the right kidney
round - slight thickening of the caudal free edge of the falciform ligament
Differentiates between left medial lobe and quadrate lobe
lesser omentum - from visceral surface of liver to stomach (hepato-gastric) and duodenum (hepato-duodenal)

13
Q

the bile duct system what flows into what

A

1) microscopic canaliculi
2) larger ductules
3) large hepatic ducts
4) common hepatic duct
- leads to cystic duct which connects to gall bladder
5) distal to cystic duct is common bile duct that runs into the duodenum entering on major duodenal papilla

14
Q

gall bladder where positioned and what is special about the cystic duct

A

lies between the quadrate lobe medially and the right medial lobe laterally
bile can flow through the cystic duct in both directions.

15
Q

blood supply to the liver

A
hepatic artery (branch of the celiac artery) - source of O2 and the portal vein - source of nurtients and atrophic factors like insulin (dual) 
all blood delivered is collecting by central veins of hepatic lobules that drain into sublobular veins that drain into large hepatic veins that eventually drain into the caudal vena cava to the right side of the heart
16
Q

The endodermal cells of the hepatic diverticulum differentiate into:

A
  • Hepatocytes (liver cells) and the bile duct system and gall bladder
  • Mesodermal cells of the septum transversum contribute to blood vessels - grows to the diaphragm
  • Blood stem cells from the yolk sac migrate into the liver to form blood islands, which form blood cells.
    (Thus at an early stage of development the liver is haemopoietic).
17
Q

dog liver why isn’t ventral border palpable, how many lobes and what lobe is special

A

presence of fat in the falciform ligament.

  • It is deeply divided into five chief lobes by fissures extending from the ventral margin.
  • The centrally located papillary process, which protrudes from its dorsal part, is the most prominent feature of the visceral surface.
18
Q

gall bladder of the dog what surface see and what does discharge depend on

A

Always appears at the visceral surface
discharge of bile depends on the activity of the duodenum. The sphincter of Oddi is a smooth muscle sphincter at the termination of the bile duct with the duodenum.

19
Q

horse liver what does axis run along, what is highest and lowest point, can it be palpated, what plane does it lay in and on what side

A

long axis runs obliquely.
Its highest point is at the level of the right kidney and its lowest point on the left side
Cannot be palpated
2/3 lies to the right of the median plane

20
Q

what does the horse liver lay against on visceral surface and describe the lobes

A

lies against the stomach, the duodenum, dorsal diaphragmatic flexure of the colon and the caecal base

1) Right lobe is the largest-irregularly quadrilateral in form on its dorsal part is the caudate lobe and process. - doesn’t have medial right lobe just all right lobe
2) Quadrate lobe is located between the right lobe and the falciform ligament which separates it from the left lobe.
3) The left lobe consists of a medial and lateral portion-lateral part is oval in outline and thickest centrally.

21
Q

horse gall bladder

A

NO GALL BLADDER, but duct system is wider to compensate.
Bile duct opens into the cranial duodenum on the papilla shared with the major pancreatic duct, about 13-15 cm distal to the pylorus - known as the hepatopancreatic ampulla.

22
Q

cow liver what contact, where sit and what is dorsal and what is ventral due to what

A

in contact with the right abdominal wall
entirely to right of median plane
the right lobe is dorsal and the left lobe is ventral - due to compound stomach on left hand side

23
Q

the visceral surface of the cow liver what is it related to and what important structure sits here

A

is related to the reticulum, ruminal atrium, omasum, duodenum, gall bladder and pancreas
e is related to the reticulum, ruminal atrium, omasum, duodenum, gall bladder and pancreas.

24
Q

lobes of the cow liver and the gallbladder

A

no distinct patterns of liver lobulation just left and right lobe
gallbladder protudes from the right lobe of the liver

25
Q

the sheep and goat liver

A

resemble cattle but smaller and lobes more distinct

26
Q

lobes of the pig and what makes it distinct

A

Left lateral (largest)
caudate lobe - doesn’t make contact with kidney so no renal impression
left medial
no papillary process
short quadrate lobe
lateral and medial right lobe
high content of interlobular fibrous tissue outlines the lobules

27
Q

birds liver what lobes present and what surfaces

A

birds lack diaphragm so embrace caudal process of the heart
larger right lobe - gall bladder
left lobe divided into deep fissue into caudoventral and caudorsal parts
- parietal surface is convex and lies against the sternal ribs and sternum
The cranioventral part of the parietal surface is concave where the lobes make contact with the apex of the heart.
The visceral surface is concave and makes contact with the spleen, proventriculus, gizzard, duodenum, jejunum and ovary.

28
Q

gallbladder in birds

A
  • Two bile ducts one from each lobe enter the distal end of the duodenum close to the pancreatic ducts.
  • Only the duct from the right liver lobe is connected to the gall bladder.
  • The pigeon, budgerigar and some parrots lack a gall bladder.
29
Q

capsule of liver what made of, what blood vessels involved and what lined with

A

thin connective tissue capsule
sinusoids - Specialised blood channels little bigger than capillaries extend between cords of liver cells:
These are lined by endothelial cells and Kupffer cells - phagocytic cells

30
Q

what are the specialised cells in the liver

A

Stellate cells

  • are pericytes, found around the sinusoids just under the endothelium,
  • Function - produce collagen - more important in disease processes
31
Q

The Liver is defined into 3 lobules based on structural or functional concepts

A

1) hepatic or classical lobule
2) portal lobule - bile
3) liver acinus - patterns of damaged for toxicity and cell death

32
Q

describe the hepatic/classical lobule

A
  • The Central vein (hepatic vein) is present in the centre of the lobule
  • The Bile duct, hepatic artery and portal vein - known collectively as the portal triad - are at the periphery of the lobule in 3 to 4 of the 6 corners of the hexagon - lympahtic vessels also found here
    hepatic cords extend outward in radial pattern from central vein
33
Q

What direction does blood flow and what direction does bile canaliculi flow in the classical lobule

A

○ Sinusoidal blood flows in a centripetal direction - toward the central vein from the corners
○ Bile canaliculi is where the bile drains in opposite direction so towards the outskirts

34
Q

portal lobule of the liver what defines as, what shape, what is in the middle and what is the boundary

A
  • Defined as a functional secretory unit of the liver - the drainage of bile
  • The portal lobule is triangular in shape – it is formed by parts of 3 adjacent classical lobules adjoining a portal canal with the bile duct as its central axis.
  • Its boundary is defined by drawing lines between the central veins of 3 adjacent classical lobules
35
Q

liver acinus what defined as what shape and the boundary

A
  • Defined as a functional unit of the liver - the supply of blood to liver tissue.
  • Is diamond-shaped, formed by the contiguous parts of 2 adjacent classical lobules
  • The boundary is defined by drawing lines between 2 adjacent central veins, via their common portal triads
36
Q

histology of the interlobular duct and gall bladder

A

interlobular - cuboidal and as move along becomes columnar

gall bladder - lined by simple columnar epithelium

37
Q

list and describe the 2 mediates of gastric emptying

A

1) cholecystokinin (released in response to fat in duodenum) causes contraction of gall bladder and relaxation of sphincter - animals without gallbladder still release this hormone to upregulate the bile concentration
2) The muscle in the gall bladder wall and duct, including the sphincter at the entrance to the duodenum is supplied by parasympathetic nerves. Vagal stimulation is therefore also a stimulus to gall bladder emptying (although weaker than that caused by cholecystokinin).

38
Q

what does bile consist of

A
  • An aqueous alkaline fluid (similar to pancreatic NaHCO3 secretion) = added by duct cells
  • Plus organic constituents = from hepatocyte activity:
    ○ bile salts
    ○ cholesterol
    ○ lecithin
    ○ bilirubin
39
Q

conjugation of bile salt what occurs and why

A

○ This conjugation step makes molecule highly polar - the steroid backbone is lipophilic, and favours interaction with other lipophilic molecules; while the amino acid conjugate is hydrophilic and favours interaction with water.
Conjugated bile salts are thus able to function as detergents, and serve to keep fats in solution in an aqueous environment. Fats are then accessible to lipase

40
Q

cholesterol and bile salts relationship

A

bile salts are derived from cholesterol and cholesterol is present in bile
bile salts keep cholesterol ina super saturated solution allowing cholesterol to be excreted in bile in much higher concentration then would be otherwise possible

41
Q

bilirubin what occurs in the intestines

A

may be deconjugated and converted by bacteria in the intestine, to urobilinogen. This is then converted to stercobilinogen, and oxidised to stercobilin which is excreted in faeces - largely responsible for giving faeces its dark brown colour.
(Although most of the urobilinogen is converted and excreted in the faeces, some is reabsorbed and goes through the liver again and a small amount is excreted in the urine).

42
Q

how much bile salts are reabsorbed by intestine and how occurs

A

95-98% of secreted bile salts are reabsorbed by the intestine
Venous blood from the ileum goes straight into the portal vein and then into the liver sinusoids.
There, hepatocytes extract bile acids very efficiently

43
Q

list 4 main purposes of metabolism

A
  • Oxidation of food to provide energy in the form of ATP
  • Food molecules are converted to new cellular material
  • Processing of waste products to facilitate secretion
  • Generation of heat - thermoregulation
44
Q

fat what is it used for and is it stored, amino acids what used for, glucose what used for how stored and what dependent on these stores

A

Fat - most released into circulation and available for energy or storage or go into the liver for processing into lipoproteins
Amino acids and glucose - go to the liver either store glucose as glycogen and amino acid go into protein synthesis
- Limit to glycogen storage not to fat storage so once reach glycogen limit store as fat (below)
Brain - totally dependent on glucose - other tissues will use other molecules so brain can have enough glucose

45
Q

postprandial what is it, what occurs

A

Postprandial - after a meal
- Dietary component high in blood - need to store
insulin is released
- Glucose is taken up by liver (also muscle and fat) to replenish glycogen stores
- Excess glucose taken up by liver and converted to TAG
- Amino acids taken up by all tissues and used for protein synthesis
- Excess aa converted to fat or glycogen

46
Q

what are the 3 steps in releasing energy from glucose

A

1) glycolysis
2) citric acid cycle
3) electron transport chain

47
Q

glycolysis what occurs, where, aerobic

A
  • Splitting of 6 C glucose into 2 x 3C, pyruvate and NADH
  • Cytoplasmic
  • Does not involve oxygen
  • Aerobic glycolysis NADH produced is reoxidised to NAD+ via mitochnodria
48
Q

citric acid cycle where occur, what occurs and what produced, how to regenerate the cycle

A

matrix - inner membrane of mitochondria
oxidative decarboxylation of pyruvate releases CO2 and acetyl-CoA that is fed into citric acid cycle
- C atoms of acetyl group are converted to CO2
- Three NAD+ are reduced to NADH
- One FAD is reduced to FADH2
- Also 1 ATP as (GTP)
Regenerate oxaloacetate to continue the cycle
times everything by two per glucose as 2 pyruvate per 1 glucose

49
Q

what are the 3 things acetyl coA can do and what concentration of oxaloacetate are present

A
  1. Go through TCA cycle - high oxaloacetate
  2. ketone bodies - low oxaloacetate
  3. Used in synthesis of fatty acids once converted to citrate - high oxaloacetate
50
Q

electron transport chain what occurs, what must have to occur

A
  • Electrons from NADH and FADH2 “bump down a staircase”
  • Each fall releasing free energy which is used to pump proton across membrane creating proton
    Gradient which allows ATP to be made from ATP synthase when proton moves back through membrane
  • Not a single step reaction
  • Chain of electron carriers with ever-increasing redox values
  • Have to have oxygen, NADH and ADP
51
Q

oxidation of fat what occurs, what called and how different from glucose oxidation

A

Carbon atoms are detached two at a time as acetyl-coA which feeds into citric acid cycle
- called Beta oxidation
Per fat molecule get a lot more energy than per molecule of glucose as one fatty acid can have many carbons that are broken off to create acetyl-coA and then each triglyceride has 3 fatty acid chains
therefore differs from glucose oxidation in preliminary formation of acetyl-coA

52
Q

what occurs with glycerol after the oxidation of fat

A

Directed to liver or kidneys where it converted to glycolytic intermediates (DHAP) - so minor

53
Q

energy release from oxidation of amino acids

A
  • Amino groups are removed
  • Carbon-hydrogen skeletons used as fuel
    Converted to pyruvate (then acetyl-coA), acetyl-CoA or to intermediates of the citric acid cycle - depends on whether ketogenic (can only produce ketones), glucogenic (produce glucose) or both
54
Q

what makes glucogenic and ketogenic amino acids

A

amino acids that are glucogenic form TCA cycle intermediates or are immediately converted to oxaloacetate then to glucose and others that only get converted to acetoacetyl coA and therefore are ketogenic -

55
Q

what occurs during fasting and what occurs during prolonged fasting

A
  • Insulin stimulated storage lowers glucose and amino acids to normal levels (chylomicrons cleared)
  • Glucagon released by pancreas
  • Stimulates glycogen breakdown to release glucose
  • Stimulates TAG hydrolysis in adipose to release FFA
    Prolonged fasting -
  • Glycogen last about 24 hours - in humans - varies in other animals
  • FFA released for muscle and other tissues (spares precious glucose for brain)
  • Muscles breakdown proteins to amino acids for gluconeogenesis
56
Q

where does gluconeogensis occur and what are the substrates

A
  • Glycerol derives from triglyceride hydrolysis
  • Lactate, pyruvate derive from incomplete glucose oxidation in muscle
  • Amino acids are from dietary sources and or protein degradation in various tissues
  • Oxaloacetate can form glucose - very important
  • Propionic acid of particular importance in ruminant animals
  • Acetyl CoA is not glucogenic
57
Q

ketogenesis

A
  • Accumulation of acetyl-CoA (beyond capacity of TCA and FA biosynthesis
  • Occurs particularly when oxaloacetate levels are low (flux through citrate synthase is impaired)
58
Q

liver structure higher proportion of body weight in what animals

A

carnivores and younger animals

59
Q

examples of what liver stores

A

storage of glycogen, lipid, vitamin B12, vitamin A, copper and iron (can get excess)

60
Q

examples of molecules synthesised from liver

A

albumin - oncotic pressure
coagulation factors - factor XII, factor VIII, prothrombin (factor II) and fibrinogen
anti-coagulant factors - antithrombin 111 and alpha and beta globulins

61
Q

haematopoiesis in the liver

A

normally takes place in the mammalian foetal liver, particularly in the perisinusoidal spaces but also in the connective tissues of the portal areas and around the larger central veins
○ haematopoietic activity usually declines post-natally but may return to the liver if there is a sustained demand for production of erythrocytes, leukocytes and/or platelets

62
Q

portal vein of the liver what percent, what does it allow and what does it supply

A

70-70%
allows rapid (first pass)
hepatic clearance of ingested nutrients, xenobiotics, infectious agents and antigens absorbed from the gastrointestinal tract
portal venous blood supplies hepatocytes with trophic factors (e.g. amino acids, insulin and glucagon (pancreas)

63
Q

hepatic artery what percent of blood flow to the liver and what is important

A

25-30%
most hepatic arterioles empty into a peri-biliary capillary plexus before emptying into the sinusoids; this arrangement drops the pressure of the incoming arterial blood

64
Q

what occurs when portal venous inflow decreases and how controlled

A

hepatic arterial inflow increases and vice versa

- this regulatory mechanism is controlled by the sympathetic nervous system

65
Q

what is the same in all parts of the liver, and what can be streamlined

A
  • the ratio of blood flow to hepatic mass is the same in all parts of the liver
  • there is probably a similar uniformity in bile drainage in health
    ○ however, portal venous blood flow can be streamlined to certain parts of the liver (e.g. from stomach and duodenum to the left lobes, and from jejunum and ileum to the right lobes)
66
Q

what are the 3 zones of the liver hepatocytes and why are they divided

A

different vulnerabilites to injury

1) zone 1 = periportal
2) zone 2 = midzonal
3) zone 3 = periacinar (or centrilobular)

67
Q

characteristics of periportal hepatocytes (zone 1)

A
  • relatively young cells that are rich in rough endoplasmic reticulum (RER)
  • closest to the incoming portal vein and hepatic arterial branches
    ○ therefore, best supply of oxygen, nutrients and other trophic factors
  • site of greatest hepatocyte mitotic activity and aerobic metabolism
  • main site of protein synthesis
  • main site of gluconeogenesis and glycogen storage
  • main site of urea cycle enzyme activity
  • main site of lipid and cholesterol metabolism
68
Q

charateristics of midzonal and periacinar hepatocytes

A

midzonal - same as zone 1 and 3
periacinar - closest to the venous outflow route from the liver
- poorest supply of oxygen and nutrients, very vulnerable to hypoxia
- hepatocytes in this zone are relatively old cells that contain little RER but are rich in smooth endoplasmic reticulum (SER)
- rich in cytochrome P450, glucuronyl transferase enzymes involved in biotransformation of lipid-soluble drugs and toxins, endogenous steroid hormones etc

69
Q

how are the hepatocytes arranged, what are sinusoids lined with, what lines the endothelial cells and what does this serve

A

anastomosing plates
sinusoids are lined by a specialised fenestrated endothelium that lacks a typical basement membrane
- the endothelial cells that line the sinusoids are supported by a loose extracellular matrix
- this arrangement promotes the exchange of macromolecules between the hepatocytes and the sinusoidal blood

70
Q

what percentage of cell population of the liver are the kupffer cells, when see, function

A

10%, usually inconspicuous by light microscopy in health - only really see when engulfing something large, filtering function and can release large amounts of potent mediators (e.g. nitric oxide, interleukin-6 and tumour necrosis factor-α)

71
Q

Perisinusoidal space, can it be seen under light microscope, when extends within, what is contained within

A

cannot be readily discerned in a healthy liver using a light microscope

  • microvilli of hepatocytes extend into the perisinusoidal space to increase the hepatocellular surface area and promote exchange of substances with sinusoidal blood
  • the perisinusoidal space contains a loose extracellular protein matrix (collagen fibres), stellate cells, nerve fibres and pit cells (natural killer lymphocytes)
  • site of hepatic lymph formation - contains 70% of total plasma proteins (including fibrinogen); it is therefore coagulable once extravasated
72
Q

how does lymph drain from the space of disse and what occurs if increase hydrostatic pressure in sinusoids and example of condition

A

Hepatic lymph drains from the space of Disse - lymphatics in the portal areas - liver hilus - lymphatics of hepatic ligaments - hepatic lymph nodes - thoracic duct
- If increase hydrostatic pressure in sinusoids more pushed into space of Disse and therefore formation of increased volume of lymph
Eg - dog was ascites due to right-sided congestive heart failure - venous blood pool in liver increase pressure, excess is a transudate as increased protein content

73
Q

stallate cells what are they, where found, what produce in health

A
  • these are specialised lipocytes (fat-storing cells) located in the perisinusoidal space immediately external to the sinusoidal endothelial cells
  • produce and maintain the delicate extracellular matrix that supports the sinusoidal endothelium
    ○ this matrix is largely made up of type IV collagen
  • in health, stellate cells store lipid droplets that are rich in vitamin A
    ○ can become greatly distended by lipid, especially in cats
    ○ also function in the control of microvascular tone and regulate sinusoidal blood flow
74
Q

what occurs to stellate cells in hepatic injury (inflammation and/or necrosis)

A

1) local release of cytokines from lymphocytes, activated of kupffer cells or injuried hepatocytes
2) stimulation of stellate cells
3) mitotic division and transformation from fat and vitamin A storing cells into collagen producing myofriboblasts
4) collagen largely deposited in perisinusoidal space - type 1 and 3
if mild - collagen may be degraded
if severe - progressive fibrosis results and is virtually irreversible - capillarisation of sinusoids - impaired perfusion of hepatocytes and compromised secretion of hepatocellular products into sinusoidal blood

75
Q

how does liver have regenerative capacity

A

1) hepatocytes have long lifespan
2) stable cells - low replication rate but maintain the capacity to divide
3) usually in post-mitotic phase but under influence of growth factors can enter cell cycle
4) periportal (zone 1) hepatocytes have the greatest capacity to replicate
- can surgically remove up to 70% of liver complete regeneration within a few weeks to normal size (but not shape)
involves mitotic division of surviving hepatocytes on the existing connective tissue scaffold - without scaffold collapse and permanent scarring

76
Q

what are some cells that are sources for new hepatocytes

A

1) oval cells (also known as ductal precursor cells)
- small bipolar epithelial stem cells located in the lining of the terminal bile ductules (canals or ducts of Hering or cholangioles)
○ located in the periportal (zone 1) parenchyma adjacent to the portal areas
- these can divide and then differentiate into either cholangiolar (bile) epithelial cells or hepatocytes
- biliary hyperplasia (proliferation of new biliary channels in the portal areas and in periportal parenchyma) is a common non-specific finding in diseased livers
2) putative multipotent periductular liver progenitor cell – derived from circulating bone marrow stem cells

77
Q

what occurs in chronic or repetitive hepatic insults

A

the parenchymal regeneration tends to be nodular (nodular hyperplasia), leading to architectural distortion

78
Q

what mainly causes liver dysfunction/failure

A

f bile outflow is obstructed or if the liver’s large reserve function and regenerative capacity are exhausted from acute massive damage (trauma or toxic insult) or chronic progressive parenchymal injury

79
Q

What are the 3 main causes of jaundice list them

A

1) Haemolysis (Pre-hepatic Jaundice)
2) Hepatocellular disease (Hepatic Jaundice)
3) Extrahepatic obstruction of Bile Flow (Post-hepatic jaundice)

80
Q

what occurs with haemolysis and how cause jaundice example

A
  • excessive breakdown of erythrocytes (red blood cells) may overwhelm the capacity of hepatocytes to take up and conjugate unconjugated bilirubin
  • e.g. intravascular (more common) or extravascular haemolytic anaemias
81
Q

main causes of hepatocellular disease that leads to jaundice where occur

A

intra-hepatic cholestasis
secretion of conjugated bilirubin into bile canaliculi is energy-dependent and is the rate- limiting step - hepatoctye injury less likely to occur so accumulation of bilirubin and spill over into sinusoids - leads to hepatocyte necrosis or canalicular rupture, local release of bile, inflammation
occurs mainly in periacinar zone 3 cells

82
Q

what are some causes of intrahepatic cholestasis

A

1) toxins - damaging SER where conjugation occurs
2) in anorexia (especially horses) - unknown
3) bacteraemia/septicaemia

83
Q

what occurs with extrahepatic obstruction of bile flow where does it first become obvious in the liver

A

obstruction of bile ducts by luminal parasites, choleliths (gall stones), inflammation, fibrosis or neoplasia (stenosis)
see distention of extra-hepatic ducst immediately proximal to obstruction and ultimately get distention of intra-hepatic ductal system
in liver first becomes obvious in portal areas and may cause extensive fibrosis around bile ducts if chronic

84
Q

when is jaundice detectable on mucous membrane, when intensity highest and most highest, when possible that yellow is carotenoid pigment

A

35μmol/L
greatest when more than one classical mechanism of hyperbilirubinaemia is operating, longer it persists, also most obvious in tissue rich with elastin (aorta, sclera)
in horses and Jersey and Guernsey cattle - yellow fat caused by dietary carotenoid pigments

85
Q

photosensitisation what is the most common form, where does it develop, how and example

A

hepatogenous photosensitisation
develops in herbivores with intra- or extrahepatic cholestasis of several days’ duration if eating green feed and if exposed to sunlight
- especially associated with toxic hepatic insults of plant or mycotoxin origin
- a classic example is facial eczema caused by the mycotoxin, sporidesmin

86
Q

Mechanism of photosensitisation, what occurs normally and what occurs when get photosensitisation

A

phylloerythrin - photodynamic agent produced by action of GI bacteria in herbivores on chlorophyll transferred to the liver and secreted into the bile normally
- in cholestasis, phylloerythrin leaks from hepatocytes into the general circulation and is deposited in tissues
in the skin, phylloerythrin is activated by absorption of ultraviolet light to produce reactive oxygen species (free radicals) that damage nuclei, cell membranes and organelles in adjacent cells

87
Q

presentation of photosensitisation

A
  • lesions are usually restricted to hairless or sparsely haired, non- or lightly pigmented skin exposed to sunlight
  • see skin hyperaemia (reddening due to increased perfusion with arterial blood), oedema, intense pruritus (itchiness), self-excoriation (self-traumatic damage), exudation and necrosis, desiccation and sloughing
88
Q

hepatic encephalopathy what animals common in, when and what is the cause and example

A

common in ruminants and horses with hepatic failure and in dogs with portosystemic shunting and (to a lesser extent) chronic hepatitis
cause - failure of hepatic detoxification functions leading to brain exposure to toxins absorbed from the gastrointestinal tract
eg - ammonia produced by bacteria in GI tract and meant to be broken down to urea - if not can cause cerebral oedema

89
Q

clinical signs for hepatic encephalopathy and example or characteristic

A

variable and non-specific clinical signs - depression, dullness, aimless movement, head-pressing, hypersalivation,
in most species is characterised by swelling of the nuclei of astrocytes (Alzheimer type 2 cells) and extensive spongy vacuolation and oedema of myelin- unravelling - reversible
horses - only see Alzheimer type 2 cells not myelin vacuolation and oedema

90
Q

where produced albumin produced, what called when have too little, what level is too little, when does this develop and what does it occur with example

A

Liver is sole source of albumin
hypoalbuminaemia only develops late in hepatic disease when at least 75-80% of functional mass has been lost - not usually chronic
- if the serum albumin concentration falls below 10-15 g/L, water begins to leave the circulation due to decreased plasma oncotic pressure - generalised oedema
○ the oedema fluid is typically a transudate (low in protein and nucleated cell count) and therefore grossly resembles water
○ Eg - Bottle jaw in sheep - oedema in the mandible

91
Q

ascites what is it what species does it most commonly develop in and what are the broad causes

A
  • ascites (accumulation of non-inflammatory oedema fluid in the abdominal cavity) associated with hepatoportal pathology develops most commonly in cats and dogs, occasionally in sheep and rarely in horses and cattle
    the abdominal effusion may be due to pre-hepatic, hepatic or post-hepatic mechanisms
92
Q

pre-hepatic causes of ascites what occurs and what type of fluid

A

conditions that lead to portal hypertension (increased pressure within the portal vein) like hepatic disease with inflammation, neoplasia, fribrosis of portal areas
venous blood from GI tract pools leading to passive congestion - increase blood in microcirculation - movement of low protein fluid from capillaries into lumen of bowel (transudate)

93
Q

post-hepatic causes of ascites, what occurs and what type of fluid

A
  • increased hydrostatic pressure in the perisinusoidal space (the space of Disse) - increased hepatic lymph formation
    e.g. post-hepatic mechanisms such as right-sided heart failure - obstruction of caudal vena cava, increase pressure in sinusoids etc
    modified transudate with an elevated protein concentration as contains proteins secreted from hepatocytes
94
Q

does the kidney do in response to ascites

A

irrespective of the cause of ascites, the kidneys respond to perceived hypovolaemia (low blood
volume) by retaining sodium and water, further compounding the ascites

95
Q

POLYURIA/POLYDIPSIA define them, and what can cause them

A
  • polyuria (increased urine volume) and polydipsia (increased water consumption) can be a manifestation of severe hepatic dysfunction, especially in dogs
    pathogenesis of PU/PD in hepatic disease is multifactorial
  • hepatic encephalopathy
96
Q

acholic faces what is it and what needs to occur and what can contribute

A
  • bile flow must be completely interrupted (e.g. complete extrahepatic bile duct obstruction or transection of the bile duct) to result in acholic (cream or white) faeces
    steatorrhoea (large amount of fat in faeces due to decrease bile acids for absorption) and chlorophyll pigments can contribute
97
Q

If suspected liver disease what test do you need to run before liver biopsy

A

laboratory tests of coagulation function in small animals with suspected liver disease to check for subclinical impairment of haemostasis - clotting factors made from the liver

98
Q

Hepatorenal syndrome what is it, when does it develop, is it reversible, mechanism

A
  • acute renal failure may develop in animals with cirrhosis and ascites
  • the renal failure is reversible if the liver function can be improved
    originally though conjugated bilirubin irritant but not now though decreased renal perfusion due to reduced blood pressure and volume
99
Q

ammonium biurate crystals what is it and when does it occur

A
  • dogs with portosystemic shunts or hepatic failure develop hyperammonaemia (increased blood ammonia concentration) and hence hyperammonuria (increased urine concentration of ammonium ions)
100
Q

List 2 miscellanous findings in liver failure and when occurs

A

1) drug intolerance - impaired hepatic biotransformation of administered drugs
2) hepatocutaneous syndrome (= superficial necrolytic dermatitis)
- especially dogs
- abnormal skin keratinisation - hyperkeratosis and crusting +/- erosion of especially high friction areas (e.g. muzzle and footpads) due to altered plasma amino acid concentrations

101
Q

developmental hepatobiliary anomalies when incidental finding when clinical significant

A

most incidental like hypoplasia of individual lobes, duplicated gall bladders
clinical significance when absebce or atresia of extraheptic bile ducts - jaundice and deficiency of fat-soluble vitamins (due to deficiency of bile acids reaching the duodenum)
affected animals may develop vitamin D deficiency rickets or vitamin K deficiency (haemorrhage)

102
Q

congenital portosystemic shunt what species most common, in small breed what usually occurs and in large breed what usually occurs

A

most common dogs and cats but can occur in any species
small breeds - usually single, large, extrahepatic shunt between portal vein and caudal vena cava
large breeds - usually single, large, extra-hepatic shunt usually persistenence of foetal ductus venosus or some anomaous vessel elsewhere in the liver

103
Q

clinical signs of animals with congenital portosystemic shunts and microscopic appearance and you rely on biopsy to confirm presence of a shunt

A

typically stunted in growth, signs of hepatic encephalopathy, liver is typically hypoplasia
microscopically - portal areas are small, increase in proliferation of hepatic arteriolar branches (compensate)
no because identical microscope lesions with hypoplasia or one or more intra-hepatic branches of portal vein or acquired portosystemic shunt

104
Q

Congenital Hepatic and Biliary Cysts what species occur in, what derived from, what content look like large and superfical cysts (what called)

A
  • congenital hepatic or biliary cysts occur in all species
  • may be derived from the intrahepatic bile duct system or from the hepatic capsule
  • content is usually clear and watery
  • large cysts may distend the abdominal cavity but most do not compromise liver function
  • single large superficial cysts that protrude from the diaphragmatic aspect of the liver capsule (so-called serosal inclusion cysts)
105
Q

ductal plate malformations what species seen in, what associated with, how classified and where located when arise early or develop late

A
  • Seen in cats (especially Persians), dogs (especially Cairn and West Highland white terriers), pigs and goats
  • often associated with polycystic kidneys (which may ultimately cause renal failure) +/- polycystic pancreatic ducts
  • ductal plate malformations are subclassified according to the calibre of the affected bile ducts and also on whether the cysts progressively expand due to fluid accumulation or are eventually obliterated by fibrosis
  • arise early are usually located centrally towards the hilus of the liver whereas those that develop late are situated at the periphery of the lobes
106
Q

displacement of the liver to where and what sometimes occurs

A

usually caudal displacement or within thorax (cranial) - common in diaphragmatic hernias
- lobe(s) strangled by a hernial ring undergo congestion and oedema (due to impaired venous drainage) and eventually venous infarction

107
Q

liver lobe torsion what occurs which lobes, hepatic rupture what can occur

A

Lobe Torsion
- especially left lateral hepatic lobe in sows and dogs
- the lobe undergoes venous infarction
Rupture
- e.g. blunt abdominal trauma
- rupture of hepatic parenchyma may lead to fatal haemoperitoneum (presence of blood in peritoneal cavity)