NUTR 3000 - Metabolic disorders

Metabolic disorders may be caused by

• A simple deficiency

• An induced deficiency

• Failure of an enzyme

• Dietary overload (as in laminitis in horses, or obesity in humans)

• Biochemistry

• Nutrition

• Genetics

Why could one enzyme not working cause full metabolic disorders

metabolism is a large network, if something goes wrong, it can cause a chain reaction causing a build up of compounds

G6PDH is

Glucose 6 Phosphate dehydrogenase

G6PDH deficiency in humans causes what conditions?

hemolysis and jaundice

Hemolysis is

the spontaneous destruction of RBC

How do you get G6DPH deficiency

inherited

Who is most susceptible to G6DPH

middle east, tropical africa, and asia

in the pentose pathway, G6P is oxidized by G6DPH to

6 phospho glucono lactone

In red blood cells, the P-P pathway is used to generate NADPH, which regenerates reduced glutathione, which protects

RBCs from oxidative damage

Favism develops when

a person with less efficient G6DPH enzyme consumes drugs (aspirin) or fava beans. The compounds oxidize glutathione faster than it's regenerated and hemolysis occurs

Favism is common in the

mediterranean

Phenylketonuria is a

phenylalanine overload

Phenylketonuria occurs in people who have

inneffective phenylalanine hyrdroxylase

What happens to the excess phenyl alanine

it breaks up in tissues, and can be excrete through the urine as phenylpyrivate

The build up of phenylalanine, if not but on a low phe diet, can cause

brain damage

depigmentation/albinism

aggression

hyperactivity

Phenylpyruvate is a

ketone, the keto analog of phenylalanine

T/F: Phenyl ketonuria is common

False, only 0.005% have it

If you have phenylketonuria you should

eat a low Phe diet, and eliminate: artificial sweeteners, meat, eggs, dairy, fish, beans, nuts

depigmentation is caused by shortage of __________

shortage of tyrosine

In PKU, why would tyrosine become an EAA

normally. we convert Phe into tyrosine when we need it, but if you cant eat Phe, you still need tyrosine. Tyrosine would become essential

MAO deficiency results from

and amine overload

Gout is caused by

uric acid overload

In humans, gout causes

-painful joint inflammation

Where is gout most often seen

in older men

chickens and birds

purines

Adenine and Guanine

Pyrimidines

Cytosine and Thymine

Purines are found in

nucleic acids and ATP

When nucleic acids and ATP are turned over, they are partly recycled and partly broken down into

uric acid

In most mammals, (some reptiles and mollusks), uric acid is broken down further into

allantoin

Allantoin, compared to uric acid and its salts, is

soluble (uric acid tends to crystallize out)

Humans lack the enzyme to converts uric acid into allantoin, which can cause

crystallization in the joints, painful

Birds are susceptible to gout because

birds and reptile excrete uric acid from deamination of proteins (gout found in T-rex remains)

What diet is advised for gout

avoid high-purine diets (meats, fish, shellfish, peas, beans, beer, wine)

What benefit might uric acid have

it is an antioxidant

Drugs for gout

colchicine, allopurinol

Neonatal hypoglycemia is cause by

glucose deficiecny

neonatal hypoglycemia is common in

pigs

Young pigs normally get glucose from

-glycogen reserve in liver

-digesting milk

What might induce hypoglycemia in piglets

-if milk doesn't contain glucose

-shivering (being cold)

Anything interfering with sucking

-competition

-sore teats

-poor milk release

-non-functional teats

-location (front teats = more milk, back teats away from head = less milk)

Young piglets have no

hair or fat

Piglet with hypglycemia become

depressed, cold, alone

Emergency treatment for hypglycemia

IP glucose and heat lamps

IP means

intraperitoneal

Peritoneum: serous membrane that lines the abdominal cavity and covers all viscera

• Serous = secretes a small amount of watery fluid for lubrication

Long term hypoglycemia treatment (management of pigs)

-foster piglet

-improve warmth of surrounds, stop drafts

-adjust farrowing crates

piglets have 30g glycogen per

kg body weight

only __% of any fat a piglet contains can be converted to glucose

5

Acidosis (laminitis) is caused by

an acid overload

How do high grain diets cause acidosis

High-grain diets contain a lot of starch, which ferments quickly in the rumen to acids, including lactic acid

• These can cause the pH of the rumen to fall

• Rumen pH is normally controlled by absorption of acids into the blood and by bicarbonate in the saliva•

• On high-grain diets, these controls can be insufficient

How much do cows salivate

~150L saliva / cow / day

Rumen pH in chronic acidosis

Rumen pH in acute acidosis

Clinical acidosis blood pH is

Fibre digetsers are inhibited below what pH?

5.8

Excess acid in the rumen can cause damage to the rumen wall, called what? What does it do?

rumen parakeratosis

allows bacteria into the blood

Blood leacing the rumen passes through the ____________ to the liver

hepatic portal vein

Bacteria from acidosis can be filtered out by the liver, but this can cause

liver abscesses

can be condemned at slaughterhouses for theses

liver abscesses are signs of ________________ acidosis

chronic

T/F: acute acidosis can be cause by cattle eating too many apples

true

If a cow is slightly unwell, production down and the pH

SARA

____________________________is helpful in treating acute cases and is often included in feedlot rations to reduce chronic acidosis

Baking soda (Na bicarbonate)

How can you use a healthy cow to treat acidosis?

Possible to wash out or empty the rumen of a cow with acidosis, then transfer some rumen contents from a healthy cow (cannulated)

Laminitis is caused by an overload of _______

acid overload

Laminitis is also called

founder

Laminae are tissues inside the

hoof

Signs of laminitis

abnormal gait, unable to stand

Laminitis is typically caused by (management)

-acute overfeeding

-sudden changes

-chronic high grain rations

-ponies on lush pasture (fructans)

Laminitis is typically caused by (other factors)

-metritis (inflamed uterus)

-pneumonia

-cold water

A fast increase in ______________ feed causes a large production of _______________ in the _____________ of horse (or rumen of cattle)

fermentable

lactic acid

colon

Lactic acid kills ___________________ bacteria, which, when they disintegrate, release _________________, such as ____________________

gram negative

endotoxins

Cell-wall glycolipids /lipopolysaccharides

Endotoxins are absorbed into blood and cause

inflammation to the hoof

separation of laminae

coffin bone push through hoof

what toxicity can also cause laminitis?

selenium toxicity

Treatments for laminitis

• Stomach pump

• Purgatives (4L mineral oil by mouth)

• Special shoes or pads

Galactosemia results from

galactose overload

When galactosemia occurs, what enzyme might not be working

Galactose-1-phosphateuridyl transferase

Galactosemia can cause

brain damage, cataract

Treatment for galactosemia

galactose-free diet (no milk)

Ketosis results from

Fat being broken down, glucose deficiency

Ketosis is aka

acetonemia

in beef cattle and sheep, ketosis occurs

before giving birth

in dairy cows, ketosis occurs after ___________

after calving

Symptoms of ketosis

drunk/depressed behaviour

ketones in blood

milk yield drops

loss of appetite

smell of acetone on breath and urine

What are the ketones?

acetoacetate, hydroxybutyrate, acetone

how to test for ketosis

ketone meter, uses a drop of blood

ketosis is likely to arise when

a lot of fat is being broken down and there is a shortage of carbohydrate

what piles up in ketosis

Acetyl CoA (which converts into the ketones

Can ketones be oxidized?

They can be oxidized and used in some tissues (muscle, brain), but only up to a limit

Treatment for ketosis

-IV glucose

-sugar or molasses

-glucocorticoid

Which cows are prone to ketosis

fat ones

What from of ketosis is most common

sub clinical

Twin lamb disease is aka

pregnancy toxemia

diabetes can cause

diabetic acidosis

LDL receptor deficiency can lead to

cholesterol overload

Cholesterol overload can be __________ based. It is called:

gene

hypercholesterolemia

Cholesterol is a precursor for

steroids and bile acids

Cholesterol has molecules which bind to

bind the LDL (low density lipoprotein) particles, which carry most of the cholesterol in the blood