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Metabolism and Excretion Flashcards

1
Q

What is ALT?

What species is it useful in?

A

Alanine aminotransferase. Cytosolic enzyme that is used to detect hepatocellular injury.

Dogs, cats, rabbits, rats and primates

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2
Q

What is AST?

What species is it useful as a marker in?

A

Aspartate aminotransferase. Cytosolic and mitochondrial marker for hepatocellular injury.

Useful in horses, ruminants, dogs and cats.

*note: this marker needs to be interpreted alongside CK and the PCV because you often get an increased AST with primary muscle injury

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3
Q

What is GLDH?

A

Glutamate dehydrogenase. Mitochondrial marker for hepatocellular injury. Used in large animals, birds, reptiles, cats and dogs. It requires greater cell damage to escape into serum

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4
Q

What is SDH?

A

Sorbitol dehydrogenase. A cytoplasmic marker for hepatocellular damage in horses and ruminants. 🇺🇸

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5
Q

What is ALP?

A

Alkaline phosphatase. A membrane bound marker for cholestasis used in cats and dogs. Has 3 isoforms: liver, bone, corticosteroid

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6
Q

What is GGT?

A

Gamma glutamyl transferase. A membrane-bound enzyme used to detect cholestasis and biliary hyperplasia in ALL domestic species

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7
Q

Liver dysfunction/ failure can manifest in different ways including…

A
  1. Jaundice
  2. Photosensitization
  3. Hepatic encephalopathy
  4. Hypoalbuminaemia
  5. Ascites
  6. Polyuria/ polydipsia
  7. Acholic faeces
  8. Haemorrhage and thrombosis
  9. hepatorenal syndrome
  10. Ammonium bifurcate crystalluria
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8
Q

Briefly describe the energy release from glucose.

A

Glucose ➡ glycolysis (pyruvate, NADH, ATP) ➡ citric acid cycle involves oxidative decarboxylation of pyruvate ➡ acetal coA

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9
Q

The gall bladder in the dog lies where?

A

Between the quad rate and right medial lobes

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10
Q

The ligaments of the liver include…

A

🔹Coronary (form a connection between the liver and the immediately joining part of the diaphragm)
🔹Falciform (begins on ventral wall of abdomen)
🔹L/R triangular (attach the liver firmly to the left and right tendinitis regions of the diaphragm)
🔹Round ligament (thickening of caudal free edge of the falciform ligament. Umbilical vein vestige)
🔹Hepatorenal ligament (caudate process to ventral surface of right kidney and caecum)
🔹Lesser omentum (visceral surface of liver to stomach and duodenum)

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11
Q

What gives pig liver the morocco leather appearance?

A

High content of interlobular fibrous tissue outlining minute liver lobules

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12
Q

Sinusoid also blood flows in a______________ direction?

What about bile?

A

Centripetal (towards the central vein)

Bile flows in a centrifugal direction (towards the portal triads)

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13
Q

The opening of the bile duct is guarded by the….?

The wall of the gall bladder (histologically)…?

A

Sphincter of Oddi (closed except during meals)

Simple columnar epithelium, mucosal crypts, LCT, lamina proprietary, submucosa, muscularis externa, serosa

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14
Q

What are the mediators of gall bladder emptying?

A

Cholecystokinin: released in response to fat in the duodenum. Contracts GB and relaxes sphincter

Vagal stimulation: GB muscle and duct is supplied by parasympathetic nerves

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15
Q

Bile is comprised of….

A

Cholesterol
Bile salts (function as detergents)
Lecithin (fat emulsifier)
Bilirubin

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16
Q

What is hepatitis?

A

Inflammation of the hepatic parenchyma

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17
Q

Which pattern of hepatitis is most likely to progress to cirrhosis?

A

Diffuse hepatitis

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18
Q

What conditions commonly lead to hepatic abscess formation in cattle?

A

🔹ruminants acidosis/ rumenitis
🔹fusobacterium necrophorum = hepatic necrobacillosis
🔹traumatic reticuloperitonitis

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19
Q

How do gross lesions of fusobacterium necrophorum-induced hepatitis differ from those caused by pyogenic bacteria?

A

F.necrophorum: produce sharply circumscribed, dry zones of coagulative necrosis with an intense margin of hyperaemia and haemorrhage. The centres of these liquefy to form conventional abscesses

Pyogenic bacteria: form abscesses with a yellow or yellow-green liquid pus.

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20
Q

What are the potential consequences of hepatic abscessation?

A

Most are asymptomatic.
Can lead to weight loss, decreased milk production in cattle.
May become encapsulated and form adhesions to adjacent viscera.
Very rarely they perforate the liver.
May erode into hepatic veins.
May spread systemically leading to toxaemia and death

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21
Q

Briefly outline the aetiopathogenesis of black disease. What gross lesions might you expect?

A

Caused by clostridium novyi, type b.
Ingested spores produce and release exotoxins which causes necrosis and expansion of the original lesion. This leads to absorption of toxins into the general circulation leading to widespread vascular injury.

Systemic oedema, rapid carcass putrification, severe subcut congestion. Lesions of larval fluke migration, one or more large (>2cm) yellow-white to red zones of coagulative necrosis with a margin of intense hyperaemia.

Large gram +ve bacilli in zones of necrosis and concentrated at margin.

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22
Q

What is bacillary haemoglobinuria?

A

Liver disease common to black disease but caused by clostridium haemolyticum. Lesions as per black disease (see below) but usually only 1 large focus of liver necrosis is present.

Systemic oedema, rapid carcass putrification, severe subcut congestion. Lesions of larval fluke migration, large (>2cm) yellow-white to red zones of coagulative necrosis with a margin of intense hyperaemia.

Large gram +ve bacilli in zones of necrosis and concentrated at margin

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23
Q

What is the typical gross pattern of lesions in multifocal (embolic) hepatitis?

What are some agents that commonly cause this?

A

BING BING BING!!! Random distributed lesions

Causes: 
Bacteraemia 
Some systemic protozoal infections (eg. Toxoplasma gondii)
Viraemia
Systemic fungal infections
Migrating parasites
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24
Q

What is a useful macroscopic clue that indicates multifocal hepatitis is likely to be due to parasitic migration?

Name some related parasites.

What are some consequences of transhepatic migration?

A

Linear or sinusoidal tunnels containing haemorrhage, necrotic debris, leukocytes and fibrin exudation are present grossly wherever the liver capsule has been breached.

Parasites: 
Fasciola hepatica 🐑🐮🐑🐮
Taenia hydatidgena 🐑🐑🐑
Ascaris suum 🐷🐷🐷
Stephanurus dentatus 🐷🐷🐷

Transhepatic migration is common but rarely fatal. Leads to economic loss at meat inspection. Can be fatal if large numbers of migrating parasites or if the parenchymal injury triggers activation of a clostridial spore (black disease or bacillary haemoglobinuria)

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25
Zonal hepatitis is an unusual pattern of hepatitis that can mimic hypoxic and toxic insults to the liver. Name 2 conditions that produce zonal hepatitis.
Canine adenovirus-1 (canine infectious hepatitis) | Equine serum hepatitis (theiler's disease)
26
What are the characteristic features of chronic hepatitis in dogs? What is known about the causes of this condition?
Characterised by: 🌼periportal interface hepatitis (especially involves lymphocytes and plasma cells) 🌼Apoptosis of periportal hepatocytes 🌼frequent progression to cirrhosis due to progressive deposition of collagen in the perisinusoidal spaces by stellate cells Causes: 🌼mostly caused by infection with hepatitis viruses A-E (esp. B and C) 🌼autoimmune hepatitis, drugs, alcohol metabolic disorders, storage disorders NOT ALL CASES ARE ACTIVE OR PROGRESS TO CIRRHOSIS
27
In which canine breeds is chronic hepatitis associated with copper storage? In which breeds is copper storage thought to be primary to cholestasis? ⭐️
``` Bedlington terrier ⭐️ West highland white terrier ⭐️ Skye terrier ⭐️ Doberman pinscher Dalmatian ⭐️ Labrador ⭐️ American and English cocker spaniel Standard poodle ```
28
What do the following terms mean? Cholangitis Cholangiohepatitis Cholecystitis
Cholangitis= inflammation of the bile ducts and their supporting connective tissues Cholangiohepatitis= infl. centered on the bile ducts of the portal areas but spreading to involve the hepatic parenchyma Cholecystitis= inflammation of the gall bladder
29
What are the typical gross lesions of chronic fascioliasis in sheep and cattle?
Lesions occur in both liver lobes but are more severe in the left lobe. 🐑 dilation of thin walled bile ducts, mild catarrhal inflammation of duct mucosa and little reactive fibrosis 🐮 bile duct fibrosis, severe duct mucosal erosion and ulceration, irregular duct stenosis
30
How do bacteria reach the biliary tree to cause cholangitis, cholangiohepatitis and/or cholecystitis? Which domestic species commonly develop bacterial cholangitis/ cholangiohepatitis? What would you expect to see grossly in the bile ducts of affected animals (acute and chronic stages)?
Bacteria may arrive haematogenously and descend the bile ducts. More commonly they ascend the bile ducts from the duodenum. Affects cats and horses and other animals sporadically. Acute: liver is swollen and soft. Few-many supparative foci, pus obvious within lumina of intra- and extrahepatic bile ducts Subacute/ chronic: fibrosis around affected bile ducts and may bridge between portal areas. Biliary hyperplasia, intra- and extrahepatic cholestasis, parenchymal atrophy, mild regenerative nodular hyperplasia of surviving hepatocytes.
31
What are the typical lesions of chronic lymphocytic cholangitis/cholangiohepatitis in cats? What is thought to be the pathogenesis of this disease?
Affects young to middle-aged cats. Chronic inflammation rich in small lymphocytes centred on the intra- and extrahepatic bile ducts. Variable degree of biliary fibrosis, biliary hyperplasia and intra- and extrahepatic cholestasis Immune-mediated pathogenesis is suspected. May involve helicobacter.
32
Outline the aetiology/pathogenesis of facial eczema in ruminants.
Aetiology: sporidesmin (mycotoxin produced by pithomyces chartarum. Ingested and carried to the liver. Excreted in bile. Irritant. Causes necrosis of intra and extrahepatic biliary epithelium, irritation of peribiliary connective tissues and blood vessels. Leads to obstructive jaundice and photosensitization. Can also cause mucosal oedema and haemorrhage in urinary bladder.
33
What is tribulosis? What is distinctive about histological lesions in the liver?
Jaundice and hepatogenous photosensitization resulting from the consumption of tribulus terrestris (aka caltrop). Caltrop contains steroidal sapogenins which may form salts with calcium ions and precipitate in the bile ducts as fine crystals. Crystals may also be found microscopically in hepatocytes, kupffer cells and sometimes renal tubules.
34
How common are gall stones in domestic animals? Why do they form and what are the potential consequences?
Occasionally. Usually of no clinical significance. However may rarely cause obstructive jaundice and/or pressure necrosis with risk of gall bladder rupture
35
What is a gall bladder mucocoele? In which species is this seen?
Accumulation of excess mucin in gall bladder. Especially in older dogs of small to medium breeds (especially cocker spaniels)
36
What are potential causes of extrahepatic bile duct obstruction?
``` 🌼cholangitis 🌼intraluminal parasites 🌼choleliths (gall stones)- rarely 🌼gall bladder mucocoele 🌼periductal fibrosis 🌼pancreatic, bile duct or proximal duodenal tumour ```
37
What is the most likely cause of bile peritonitis? What are the potential consequences?
Traumatic rupture of the extra-hepatic biliary tree. Can also result from spontaneous rupture of an inflamed/infected or obstructed/infarcts during segment of the extrahepatic biliary tree. Can lead to generalised peritonitis which may be septic (if caused by bacteria)--> life threatening
38
Outline the typical lesions of facial eczema in ruminants.
Acute: swollen jaundiced liver, oedematous gall bladder and portal connective tissues, oedematous thinking of bile ducts, parenchymal bile infarcts Chronic: firm, fibrotic left lobe with fibrous thickening of the bile duct walls. Hypertrophy of the right lobe
39
The three major volatile fatty acids produced (from pyruvate) during ruminant CHO digestion include....
Acetate Proprionate Butyrate
40
What is the only VFA that a ruminant can make glucose out of? By what pathway does it do this?
Proprionate (propionic acid) Methylmalonate pathway (propionate ➡️ propionate CoA ➡️ methylmalonyl CoA ➡️ succinate)
41
In order to produce succinate (and then oxaloacetate and then glucose) in a ruminant, what 3 things are needed? What does the rumen need in order to make B12?
CoA, biotin, Mg++ Cobalt
42
What is the major product of CHO digestion and ruminants and the only VFA present in the blood?
Acetic acid
43
In what ways can drugs move across cellular membranes in order to be absorbed?
Filtration, passive diffusion, active transport, facilitated diffusion, endocytosis
44
What is meant by the term volume of distribution? Why is it important?
The volume of body water in which a drug appears to be dissolved, after it has distributed throughout the body. Vd=x/c (where x is the amount administered and c is the concentration at the time of administration) Important bc it tells us how much drug you need to give in order to get a certain concentration in the plasma
45
Describe the 2 phases of metabolism in the liver.
Phase 1: enzymes act to introduce reactive and polar groups into their substrates. Phase 1 reactions may occur by oxidation, reduction, hydrolysis, cyclisation/decyclisation and they involves the cytochrome P450 superfamily of enzymes. Phase 2: synthetic reactions that add groups by conjugation to increase water solubility and decrease toxicity.
46
What is bioavailability of a drug?
Proportion of an oral dose that reaches the systemic circulation.
47
How are we able to visualise the portal vasculature using radiographs?
Mesenteric angiography
48
What three processes contribute to control the volume and composition of urine?
1. Filtration of blood plasma to create glomerular filtrate within the bowman's space 2. Tubular reabsorption of water and salts from glomerular filtrate 3. Tubular secretion (largely by active transport)
49
The cuboidal epithelial cells of the PCT are rich in what? Why?
Mitochondria and rough endoplasmic reticulum. They synthesise abundant amounts of ATP which is needed to power active transport mechanism in order to recover important nutrients
50
Describe how the Na/K ATPase pumps in the PCT work?
They're located on the basolateral membrane of the cell. They regulate intra cellular sodium levels and thereby cell volume by moving sodium out of the cell into the extracellular fluid.
51
What is azotaemia?
Increase in any non-protein nitrogenous waste (urea and creatinine) that often occurs as a result of decreased glomerular filtration rate. It occurs when there is a 75% or more loss
52
What is uraemia?
A clinical syndrome associated with fluid, electrolyte and hormone imbalances and metabolic abnormalities, that develops with deterioration of renal function
53
What is a urine specific gravity?
Test which indicates the ability of tubules to reabsorb or excrete water. It reflects urine osmolality/concentration
54
What are the highly concentrated USG values for the following species: 🐱🐶🐴🐮🐷🐑🐦
🐱1.035 🐶1.030 🐴🐮🐑🐷1.025 🐦1.020
55
What do we need to consider when using the USG to assess renal function?
``` Hydration status Serum electrolytes External factors (eg. Hypercalacemia, hyperadrenocorticism) Drug reactions (eg. Diuretics) Effect of proteinuria, glucosuria. ```
56
The basic unit of the kidney is the ____________ which is comprised of ___________ and ____________. The papilla projects into an expanded area of the ureter called the __________ or a branch of it (calyx).
Renal lobe Cortical cap Medullary pyramid Pelvis
57
Based on the macroscopic appearance, which animals have unilobar and which have multilobar kidneys? What about based on the presence of primitive lobes?
Macroscopic: Unilobar: rodents, rabbits, dogs, cats, sheep, goats and horses Multipolar: pigs, ox Primitive lobes: Unilobar: rodents and rabbits Multilobar: pigs, ox, dog, cat, sheep, goats, horses
58
What is the order of vessels blood will pass through upon entering the kidney?
Renal artery ➡️ interlobar artery ➡️ arcuate artery ➡️ interlobular artery
59
The glomerulus is a tuft of porous capillaries supported by mesangial cells. The capsule comprises 2 epithelial layers. Describe these:
The outer layer is the parietal and is simple squamous epithelium lying on thick bm. The inner layer is the parietal epithelium and is comprised of podocytes
60
``` Describe the epithelium of the following nephron components: PCT Thin LoH DCT Collecting duct ```
PCT: simple cuboidal. Apical surfaces have a brush border LoH: simple squamous. (Can be identified from capillaries by wider lumen, rounder nuclei which bulge into lumen and more numerous cells) DCT: simple cuboidal with no brush border. Larger lumen than PCT Collecting ducts: simple cuboidal
61
What three components comprises the juxtaglomerular complex?
Macula densa (closely packed cells of the DCT in contact with the vascular pole of the renal corpuscle). Juxtaglomerular cells (modified smooth muscle cells in afferent arterioles. Act as baroreceptors). Mesangial cells (ellipsoid cells between arterioles and macula densa extending into the glomerulus
62
What is the trigone?
The triangular area outlined by the ureteral openings into the bladder and the converging mucosal folds at the neck of the bladder
63
How is the bladder stabilised within the pelvis?
Three ligaments- two lateral ligaments that extend laterally from the body wall to the bladder. One ventral ligament lies in the median plane and extends from the bladder to the body floor
64
Regulatory renal failure occurs when there is ______% loss of nephron function Excretory failure occurs when there is ______% loss of nephron function Biosynthetic failure refers to.....? Increased serum SDMA occurs at ____% loss of nephron function
>/= 66% >/= 75% Decreased production of erythropoietin (non-regenerative anaemia) >/= 40%
65
What may cause increased urea concentrations in the urine? Why is it not helpful to assess renal function in ruminants?
``` 🔹Pre-renal causes - decreased renal perfusion with dehydration -high protein diet -GIT haemorrhage or protein loss 🔹Renal insufficiency -loss of nephron function 🔹Post renal causes -urinary obstruction -uroabdomen ``` Excretion of urea is dependent on nitrogen intake. Ruminants excrete majority of urea through rumen and horses excrete urea in large intestine
66
What may cause increased creatinine levels? | (In what species is it an insensitive marker?)
``` 🔹Decrease in GFR -pre-renal (less so than urea), renal or post renal 🔹Training or rhabdomyolysis 🔹Large muscle mass 🔹Jaffe reaction? ``` (🐦🐦🐦🐦)
67
What is SDMA?
Symmetrical dimethylarginine. Released with proteolysis and excreted through kidneys. Therefore, it serves as a marker for GFR. Cannot differentiate pre-renal from renal azotaemia.
68
What are the urine protein:creatinine (UPC) ratios to indicate severity of proteinuria?
UPC <0.5 Normal UPC 0.5-1.0 Borderline proteinuria UPC >1.0 Significant proteinuria (tubular or glomerular) UPC >3.5 Marked proteinuria (highly likely glomerular)
69
Describe and provide an example of a transdermal drug.
Transdermal means that the drug is applied to the skin and is absorbed through the skin layers to then circulate within the body. An example is the -mectin group of anti parasitics The drug may also disperse in the fat layer on the skin surface (eg. Imidacloprid)
70
What factors may affect drug distribution?
Molecular size Ability to bind to plasma proteins Lipid solubility
71
What may cause an increase in C-ALP in dogs?
Exogenous corticosteroid admin Chronic stress Hyperadrenocorticism
72
In small breeds of dogs, what might an increased serum bile acid level indicate?
PSS or microvascular dysphasia (portal hypoperfusion)
73
In what case might we see acanthocytes?
Seen with shear liver injury and diseases which alter lipid composition
74
Cloudiness in urine can reflect...
``` Mucus Cells (leukocyte, epithelial, casts) Crystals Bacteria Storage ```
75
What causes hyaline cast formation?
They are tamm-horsfall proteins. Physiologic causes include strenuous exercise, dehydration, oliguria, proteinuria (accumulate in slow flow)
76
What do granular casts indicate? In what cases are waxy casts seen? What might a leukocyte cast indicate?
Renal tubular necrosis Oliguria, nephron obst., chronic renal failure, end stage renal disease Pyelonephritis
77
What factors may impair ADH action?
``` Hypokalaemia Hypercalcaemia Corticosteroids Endotoxins Pyelonephritis ```
77
What may cause proteinuria?
🔹Glomerular disease -increase in the amount filtered 🔹Tubular dysfunction -inability to reabsorb filtered protein 🔹Haemorrhage 🔹Inflammation of urinary tract -cystitis -pyelonephritis 🔹Genital tract disease -pyometron -prostatitis -vaginitis 🔹Pre-renal causes -physiologic (transient increase in glomerular permeability) ->caused by systemic stressor such as fever, dehydration -increased protein load to kidney

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