Lecture 3 - Acute Inflammation Flashcards
What is Inflammation?
The response of living tissue to injury
What is the aim of acute inflammation?
Limits damage
What does it mean by referring to acute inflammation as stereotyped?
The response is the same regardless of the damage
What is the relative duration of acute inflammation?
Short lived
What are the 2 phases of acute inflammation?
Vascular Phase
Cellular Phase
Generally, what happens in the vascular phase of inflammation?
Change in blood flow and accumulation of exudate
Generally, what happens in the cellular phase of acute inflammation?
Delivery of neutrophils
What can cause inflammation?
Pretty much anything
Trauma
Micro-organisms
Hypersensitivity
What are the 5 clinical signs of acute inflammation?
Rubor
Calor
Tumor
Dolor
Functio laesa
What does Rubor mean?
Redness
What is Calor?
Heat
What is Tumor?
Swelling
What is Dolor?
Pain
What is Functio laesa?
Loss of function
What are the 3 changes that happen in the Vascular phase?
Vasoconstriction
Vasodilatation
Increased permeability
What signs does the vasodilation stage of the vascular phase of acute inflammation cause?
Calor
Rubor
What is Starlings Law?
The movement of fluid through the blood vessel is controlled by the balance of hydrostatic pressure and oncotic pressure
What is hydrostatic pressure?
The pressure exerted on a vessel wall by fluid
What is oncotic pressure?
The pressure exerted by proteins trying to draw fluid back into blood vessels.
What happens in the increased permeability stage of acute inflammation?
Plasma proteins move into interstital space
Increased interstitial oncotic pressure and decreased capillary oncotic pressure
Fluid is drawn out by the interstitial oncotic pressure and capillary hydrostatic pressure into interstitial space
What affect does the fluid being drawn out of the blood vessels have on the blood in acute inflammation?
Increased viscosity
Reduced blood flow through vessel
What is Stasis?
When blood flow is reduced/flows more slowly through vessels since its thicker
What is exudate?
Protein rich fluid
How is exudate produced?
INCREASED VASCULAR PERMEABILITY produces protein rich fluid
Produced in inflammation
What is transudate and when is it produced?
Fluid produced as a result of increased capillary hydrostatic pressure and reduced oncotic pressure
VASCULAR PERMEABILITY DOESNT CHANGE
What conditions produce transudate?
Heart failure
Hepatic failure
Renal failure
How is transudate produced in heart failure?
Blood pools in blood vessels increasing hydrostatic pressure
How is transudate produced in hepatic failure?
Liver responsible for producing plasma proteins
Hepatic failure = decreased oncotic pressure
What are the 3 ways by which blood vessels increase their permeability?
Endothelial cells retract (become smaller)
Direct injury to endothelial cells
Leukocyte Dependant injury to endothelial cells
What stimulates the retraction of endothelial cells?
Histamines
Nitric oxide
How is the vascular phase effective to minimise damage?
Fluid in interstital spaces dilutes toxins
Exudate delivers proteins (fibrin- mesh limits spread of toxin)
Where does the fluid released into the interstitial space drain to?
Lymph nodes
What is the main white blood cell involved in acute inflammation?
Neutrophil
What is a key feature of a neutrophil?
Tri-lobular nucleus
What affect does stasis have on the blood cells in the vessel?
Margination
What is margination?
When the cells migrate to the borders of the blood vessels
What are the 4 steps to neutrophils escaping vessels?
Margination
Rolling
Adhesion
Emigration
What is another word for emigration?
Diapedesis
What are the 2 adhesion molecules important in the migration of neutrophils from blood vessels?
Selectins
Integrins
Which adhesion molecules are responsible for rolling of neutrophils?
Selectins
What is the strength of the bonds formed between the Selectins on the endothelial cells and the neutrophils?
Weak bonds
Where are Integrins located?
Surface of neutrophil
What is the function of Integrins on neutrophils?
Adhesion when they are in the high affinity state
What is chemotaxis?
The movement of cells along an increasing chemical gradient of chemoattractants
Give some examples of chemical attractants:
Bacterial peptides
Inflammatory mediators
What do neutrophils do?
Phagocytosis
Release inflammatory mediators
Briefly describe how a neutrophil phagocytoses a pathogen:
Cytoplasm extends around pathogen
Forms phagosome
Lysosome fuses with phagosome forming phagolysosome
Phagolysosome digests pathogen
How do neutrophils know what to target and destroy?
Pathogen covered in markers/labels called opsonins
What is opsoninisation?
When a pathogen is labelled by proteins for destruction
What are 2 examples of opsonins?
Fc (antibody)
C3b (complement protein made as part of innate immunity)
What produces complement proteins like C3b?
Liver
What is the cellular phase?
The migration of neutrophils into the interstitsium and destroying the opsoninised pathogens
How is the cellular phase effective?
REMOVES:
Pathogens
Necrotic tissue
RELEASES:
Inflammatory Mediators
What are inflammatory mediators?
Chemical messengers that control and coordinate the inflammatory response
What inflammatory mediators trigger vasodilation?
Histamine
Serotonin
Prostaglandins
What inflammatory mediators trigger increased vascular permeability?
Histamine
Bradykinin
What inflammatory mediators are chemoattractants triggering chemotaxis?
C5a
IL-1
Bacterial peptides
What inflammatory mediators cause fever?
Prostaglandins
IL-1
IL-6
What inflammatory mediators cause pain?
Bradykinin
Prostaglandins
Substance P
What are the 2 types of complications of acute inflammation?
Local
Systemic
What is meant by a local complication?
Specific to 1 anatomical area
What is meant by a systemic complication?
Affecting the whole body
Why can acute inflammation cause acute local complications?
Swelling my compress tubes like airways/ intestines
Give an example of an acute inflammation that would restrict breathing:
Epiglottitis (Epiglottis)
How can acute inflammation cause cardiac tamponade?
Acute inflammation of pericardial sac will cause exudate to accumulate in pericardial space compressing the heart
Why do burns cause rapid dehydration?
Acute inflammation of area causes lots of exudate to be produced
Exudate will be directly exposed to air so will rapidly evaporate
What is essential when treating a burns patient?
Aggressive IV rehydration
What are pyrogens?
Type of inflammatory mediator that act on the hypothalamus to alter the body’s temperature/thermostat
What are NSAIDS?
Non-steroidal Anti Inflammatory Drugs
What is a common systemic complication of acute inflammation?
Why does this happen?
Fever
Neutrophils produce pyrogens as an inflammatory mediator which go to the hypothalamus leading to the base thermostat being increased
What is the function of NSAIDs?
Reduce fever, pain and inflammation
How do NSAIDs reduce fever, inflammation and pain?
Stop production of Prostaglandins
Block Cox enzymes needed for their production
What is Leucocytosis?
Increased production of white blood cells
How is Leucocytosis a systemic complication of acute inflammation?
Inflammatory mediators act on bone marrow (IL-1)
Which white blood cell is going to be elevated in a bacterial infection?
Neutrophils
Which white blood cell is going to be elevated in a viral infection?
Lymphocytes
What is the Acute phase response?
Series of vague signs and symptoms indicating infection, inflammation or trauma
What are the acute phase response signs/symptoms?
Malaise
Reduced appetite
Altered sleep
Tachycardia
What are the acute phase proteins?
C-Reactive protein
Fibrinogen
What is CRP used for in hospitals?
Tested as a marker of severity of acute inflammation/infection
What happens in septic shock?
Huge release of chemical mediators
Widespread vasodilation
Hypotension (BP drops as TPR drops)
Multiple organ failure due to poor perfusion of organs
What happens after acute inflammation has been completely resolved?
In terms of the:
-Inflammatory mediators
-vessel permeability
-neutrophils
-exudate
Mediators have short half life so degrade
Vessel permeability back to normal
Neutrophils undergo apoptosis and get phagocytose
Exudate drained to lymphatics
What happens if substantial tissue damage has occured following acute inflammation?
FIBROSIS
(Repair with connective tissue)
Where is the appendix?
Hangs of caecum which is a part of the large intestine of the right side of the body
How does appendicitis usually occur?
Lumen of appendix blocked by fecal matter (Faecolith)
Bacteria accumulate and so does exudate
What are the concerns with appendicitis?
The increased pressure due tot build up of exudate and bacteria may lead to the burst of the appendix exposing contents of large intestine to abdomen
What organisms can cause Pneumonia?
Streptococcus pneumoniae
Haemophilus influenzae
What is the normal process for pneumonia?
Infection of lungs
Lungs fill with fluid (exudate) following inflammation
What are the signs and symptoms of Pneumonia?
Shortness of breath (Dyspnoae)
Cough
Sputum
Fever
What are the risk factors for pneumonia?
Smoking
Pre-existing lung condition
(COPD, asthma, malignancy)
What occurs in bacterial meningitis?
Inflammation of the meninges
What are the meninges?
The protective layer between the brain and the skull
What are the signs and symptoms of bacterial meningitis?
Headache
Neck stiffness (meninges on spinal cord)
Photophobia
Altered mental state
What is an abscess?
An accumulation of dead and dying neutrophils
Why are abscesses associated with liquefactive necrosis?
The neutrophils release all of their enzymes
What are the 3 serous cavities of the body?
3Ps
Pleural space
Peritoneal space
Pericardial space
What is accumulation of fluid (exudate) in the abdomen called?
Ascites
With a patient with pleura effusion, why would you test the fluid?
To check for exudate (protein rich) to see if acute inflammation is happening
What are some rare disorders of acute inflammation?
Hereditary angio-oedema
Chronic granulomatous disease
Alpha-1 antitrypsin deficiency
What is Alpha-1 antitrypsin deficiency?
How does it present?
Low levels of alpha-1 antitrypsin
Bad since it inhibits proteases released by neutrophils at tissues
If absent the proteases can breakdown self tissues like in the lungs
Emphysema and liver cirrhosis
How does Hereditary angio-oedema present?
Cutaneous anti-oedema
Recurrent abdominal pain
If a patient has Haemoptysis and chest pain, what sort of diseases must be considered?
TB (Tuberculosis)
Lung cancer
What is sarcoidosis?
How does it present?
Condition where bodies immune system over reacts
Enlarged lymph nodes
Granulomas
How are prostaglandins produced?
From cell membrane phospholipids
