clinical and pathological changes seen in inflammation and sepsis Flashcards
Define pathogenecity
Ability of a microbe to damage the host
Define virulence
Measure of how effectively a microbe causes damage
When do clinical signs of bacterial infection present?
When pathogenecity exceeds the body’s defences
What causes tissue damage in infection?
Bacterial toxins
Inflammatory response
Immune response
What are the 3 possible outcomes of a bacterial infections
Host clears infection
Carrier state (persistent infection)
Clinical disease (acute, subacute, chronic)
Describe the clinical signs of the inflammatory response
Systemic - Pyrexia, Increased HR and RR
Local signs - pain, heat, swelling, erythema
Pus – neutrophils (acute)
Granulomas – macrophages (chronic)
Describe the cardiovascular clinical signs of bacterial infection
Congested mucous membranes (“brick” or dark red)
Toxic line (purple line in gums near teeth – horses)
Describe the clinical pathology of inflammation seen in bloods
Neutrophils:
- Greater number
- left-shift (younger)
- toxic change (dysmaturation)
Acute phase proteins:
- fibrinogen
- CRP, SAA, haptoglobin
Cardiovascular:
- acid base (metabolic acidosis, lactate)
Coagulopathy:
- platelets, coagulation time, FDPs
What is the difference between bacteraemia and septicaemia?
Bacteraemia – Presence of bacteria in the bloodstream, but not necessarily multiplying
Septicaemia – Bacteria actively replicating in circulation, leading to systemic infection
Diagnosis – Rarely visible on blood smears, confirmed via blood culture
How do neutrophils appear in inflamed tissues?
Number assessment:
- Subjective: Microscopic examination
- Objective: Counting in effusions using lab analysers
Degenerate neutrophils – Seen in bacterial infections (cells take up water, nuclei swell)
Non-degenerate neutrophils – Seen in sterile inflammation (e.g. autoimmune disease)
What is the role of macrophages in inflamed tissues?
Clear debris & pathogens from inflamed areas
Increased macrophage count suggests chronic inflammation
Activated macrophages have foamy/lightly vacuolated cytoplasm
Describe the neutrophil response in dogs and cats
High marrow neutrophil reserve - responds quickly to infection
Rapid regenerative capacity
Neutropenia (low neutrophils) is rare, seen only in severe cases where demand exceeds production
Describe the neutrophil response to inflammation in cattle
Low neutrophil reserves → Slow response to inflammation
Early inflammation → Neutropenia due to slow replenishment
Chronic inflammation → High neutrophil count due to long-term stimulation
Cattle are good at walling off infections (e.g. abscesses in thorax/abdomen)
What does the term “left shift” mean in neutrophil maturation?
Left shift occurs when immature neutrophils appear in circulation due to high demand
Instead of only mature segmented neutrophils, you see:
- Band neutrophils (mild left shift)
- Metamyelocytes, myelocytes, or earlier precursors (severe left shift)
Indicates strong inflammatory stimulation
What is the difference between a regenerative and degenerative left shift?
Regenerative Left Shift:
- Increased mature neutrophils with some immature forms.
- Bone marrow keeps up with demand = Better prognosis.
Degenerative Left Shift:
- More immature neutrophils than mature ones.
- Bone marrow cannot keep up with demand = Poor prognosis
What does “toxic change” in neutrophils indicate?
Not caused by bacterial toxins, but linked to severe inflammation
Driven by cytokine stimulation during strong inflammatory responses
More severe toxic change = worse prognosis
What are the morphological features of toxic neutrophils?
Foamy cytoplasm – Due to dispersed organelles
Diffuse cytoplasmic basophilia – Persistent cytoplasmic RNA staining blue
Döhle bodies – Blue-grey cytoplasmic structures (rough endoplasmic reticulum/RNA)
- can be normal in cats
Asynchronous nuclear maturation – Mature-looking segmented nucleus, but immature chromatin structure
How is toxic change different from a left shift?
Toxic change – Morphological abnormalities in mature and immature neutrophils due to severe inflammation
Left shift – Increased numbers of immature neutrophils in circulation due to high demand
Both can appear together in severe infections
What do neutrophil inclusions indicate?
Uncommon findings in blood smears but may indicate infection, inflammation, or genetic disorders
Some infections directly invade neutrophils, while others cause secondary morphological changes
Give examples of causes of neutrophil inclusions
Bacterial
- Ehrlichia, Anaplasma
Viral
- Canine distemper
Protozoa
- Toxoplasma, Hepatozoon
Fungi
- Histoplasma
Hereditary/metabolic
- Chediak-Higashi, Birman cat anomaly, mucopolysidosis
What happens in septic shock?
Severe systemic inflammation due to infection
Cytokines & endotoxins cause metabolic failure & circulatory collapse
Leads to poor oxygen delivery, organ dysfunction & lactate accumulation
How do cytokines and endotoxins affect cellular metabolism in sepsis?
Cytokines & endotoxins inhibit pyruvate dehydrogenase, preventing pyruvate from entering the Krebs cycle
Instead, pyruvate is converted to lactate, leading to lactate accumulation
Cells switch to anaerobic metabolism due to oxygen extraction failure
How does vasodilation contribute to tissue hypoxia in septic shock?
Widespread vasodilation → Blood moves too slowly in some areas, too fast in others
Oxygen bypasses hypoxic tissues, leading to poor oxygen extraction
Venous blood remains oxygen-rich, but tissues still suffer from hypoxia
How does severe inflammation lead to coagulation abnormalities?
Cytokine storm activates clotting cascade
Leads to disseminated intravascular coagulation (DIC)
Platelets become hyperactive, causing microthrombosis & depletion of clotting factors
What happens in DIC (Disseminated Intravascular Coagulation)?
Excess clot formation → Microthrombosis & organ damage
Clotting factor depletion → Uncontrolled bleeding
Often seen in sepsis, systemic inflammation, and trauma
How does DIC create a vicious cycle of inflammation?
- Inflammation activates neutrophils
- Neutrophils release DAMPs (damage-associated molecular patterns)
- DAMPs promote coagulation & reduce fibrinolysis
- Coagulation further stimulates inflammation, worsening process
