Essential tissue destruction

Initiation of endotoxaemia
-once in blood stream lipid A binds to PBS binding protein (LBP) which binds to CD14 on monocytic cells which actives pattern receptor molecules on cells like TLR (toll like receptors)
this will effect the transfer of LPS to MD2 which stimulates monocytes, dendritic cells, macrophages to up-regulate the production of cytokines, nitrous oxide and iosanoids (prostaglandin) for inflammation
inflammatory cytokines like IL1&6 will induce a release of acute phase proteins, like fibrinogen, this results in haemodynamic (blood flow) derangement (disturbance), abnormal body temp, multiple organ failure etc.

Small amount of lipid A = protective inflammatory response

Large amount of lipid A = excessive inflammatory response which is auto destructive

consequences of endotoxameia
the initial production of cytokines by the monocytes and macrophage leads to;
-the production of a variety of cytokines including prostaglandins
-stimulation of the coagulation cascade
-stimulation to the alternative complement pathway

fever is a clinical sign of endotoxameia fever, IL-1 stimulates the production of prostaglandin E2 in the hypothalamus which stimulates CAMP to be produced therefore increasing the temp set point of the thermoregulatory centre, this leads to mammals shivering to increase heat production and vasoconstriction in the skin which reduces heat loss

Lipid A initiates an immune response when it binds to LBP which then ends to CD14 on monocytic cells which results in complex activates pattern receptor molecuesl like toll like receptors which effects the transfer of LPS to MD2 which stimulus monocytes, dendritic cells, macrophages and B cells to up-regulate the production of proinflammatory cytokines

vascular effects of endotoxin
there is vasodilation which causes decreased blood flow to tissues.
vasoactive amines like histamine causes the leakage of capillaries and this causes the BP to go down and there is oedema because the fluid increases in the interstitial, there will be microalbumin forming, the capillaries will be destroyed and this leads to necrosis
decrease in tissue perfusion and therefore causes metabolic acidosis
there is cardiac depression, the heat will beat faster however its no effective which causes a decrease in cardiac output

endotoxin effects on coagulation
increase in endothelial leakage, there is a release and activation of large quantities of clotting factors result micro emboli (blood clots) within the micro capillary bed and this leads to clotting factor depletion, this is called disseminated intravascular coagulopathy (DIC)
animals effected also have multi-organ failure due to ischaemic (deficient supply of blood) necrosis
por tissue perfusion leads to metabolic acidosis

Endotoxaemia causes acute respiratory distress syndrome
there is an increases amount of cytokines by activated macrophages causing hyperinflammation in the lungs wiht hypertension (high blood flow)
there is an increase of fluid in r the interstitial
there is a decrease in surfactant, diffusion becomes shit, CO2 going out struggle and O2 struggles to get in which causes respiratory acidosis
this also causes cyanosis (lung becomes blue)

Small capillaries are present and the haemorrhages come from shock in the late stage

The animals can’t expel the CO2 and there is an issue with the kidneys and this is for the acidosis, cells produce surfactant are damaged
causes oedema
hypotension and hypertension

Laminitis
inflammation of the lamellae
endotoxaemia can be the cause, it can lead to an increased inflammation of the hoof due to increased capillary pooling
increase in inflammatory cytokines can result in production of matrix metalloproteases which breakdown the basement membrane of the lamella
this leads to a decrease in nutrient and O2 supply to the lamellae will result in ischaemic (deficient supply of blood) necrosis of the lamellae
so the blood flow to the lamellae which is damaged cause the fuck up of gown and there is the rotation of petal bone

D) The inflammatory response in the hoof causes neutrophils to degranulate and damage the hoof lamellae

Diagnosis of endotoxaemia

• clinical examination; fever, rapid breathing, pulse is weak and rapid

• haematology and blood chemistry; metabolic acidosis, low levels of O2 in the blood

• Post-mortem examination

• endotoxin activity assay= chemically-luminescence test which tests if IgA ab have bound to toxin A

• Lipoplysaccaride (LBP) binding protein which is detected in a sandwich or competitive ELISA, it will level the levels of LBP

• limulus amoeba assay

treatment of endotoxaemia

• control source of endotoxin, treat colic mastitis etc. antibiotic therapy, surgical removal of dead tissue

• hydration; increase blood volume ensure cardiac output is maintained

• hyperimmune plasma; protect animals at risk before clinical signs are present

• polymixin B its an antibiotic that binds lipid A allowing lipid A to be cleared from the body

• non-steroidal anti-inflammatories; reduces the production of vasoactive amines in a hydrated animals

Transduction

conjugation

transduction
-lytic cycle
they have a long tail which attacked to bacterial cells and their inject their DNA into the bacteria using a pumping action.
The DNA forms a circle and encodes the bacteria to replicate and then the bacteria will rupture releasing the new phage virions
-lysogenic cycle
phage attaches to host cell and injects DNA
phage DNA circularise
phage DNA integrates within the bacterial chromosome by recombination becoming a prophage (genetic material)
lysogenic bacterium reproduces normally
many cell divisions
prophage may excise from bacterial chromosome by another recombination event initiating a lytic cycle

conjugation is when 1 bacterium transfers plasmid DNA to another bacterium of the same species via sexual pill

exotoxins classified
defined by their model of action
- type 1; activated directly on host cell plasma membrane receptors
-type 2; damage cell membranes
-enter cell and after cell processes=intracellular toxins
can be defined by the tissue they affect;
-tissue toxins-histotoxins/cytotoxins
-interstinal toxins= enterotoxins
-peripheral and CNS toxins= neurotoxins

-suckling 1 dry; enterotoxigenic Escherichia coli
EC will grow rapidly, adhere to the brush borders of intestinal epithelium and produce heat-labile or heat stable enterotoxins, these toxins cross into the cell cytoplasm, heat labile toxins activates adenyl cyclase easing cAMP levels which stimulates the transmembrane chloride transporter to secrete cl and h2o
heat stable toxins binds to membrane guanltae cyclase stimulating the production of cGMP which stimulates transmembrane channels to secrete Cl and bicarb ion bring H2O, this fluid loss can result in rapid dehydration which is fatal in young animals