W7 Pathophysiology of infections and clinical infection markers

Question 1

Mechanisms of Pathogen-Host Interaction:
What is adherence?

Answer 1

• Mechanisms to try and attach to host cells to facilitate colonisation
• Pili/fimbriae
• Adhesins
• Biofilms

Question 2

Mechanisms of Pathogen-Host Interaction:
What is immune evasion?

Answer 2

Pathogens using strategies to hide from host immune system
1. Antigenic variation
2. Intracellular survival
3. Inhibition of Phagocytosis

Question 3

Mechanisms of Pathogen-Host Interaction:
target for tissue damage?

Answer 3

Toxins
Inflammation
Host cell death (apoptosis)

Question 4

What is Colonisation?
What is Invasion?

Answer 4

• Pathogens establish residence at the site of infection
  (ingestion in contaminated food, colonisation of the cecum, non-invasive infection- febrile gastroenteritis)
• Pathogens breach host barriers and gain access to deeper tissues
  (intestinal epithelial into the mesenteric lymph nodes and portal circulation)

Question 5

What is proliferation?

What is dissemination?

Answer 5

• Pathogens multiply and spread within the host
  (replication in the liver and spleen)
• Pathogens spread to other sites within the host or to new hosts
  (in the blood, brain infection e.g. meningitis, Martens-fetal infection e.g. abortion and still birth)

Question 6

What is the definition of pathology?

Answer 6

The medical discipline that describes conditions typically observed during a disease state. Describes the abnormal or undesired condition.

Question 7

What is the definition of Physiology?

Answer 7

The biological discipline that describes processes or mechanisms operating within an organism.

Question 8

What is the definition of Pathophysiology?

Answer 8

A convergence of pathology with physiology. Seeks to explain the functional changes that are occurring within an individual due to a disease or pathologic state.

The disordered physiological processes associated with disease or injury. Disruption of the body’s homeostasis; alteration in function, metabolism, organ systems and the mechanisms involved.

Pathophysiology is the study of the underlying mechanisms by which diseases occur and develop, and the study of the changes by diseases within the body. It provides A theoretical basis for the preventive prevention, diagnosis and treatment.

Question 9

What is the difference between signs and symptoms?

Answer 9

Signs- measurable and objective
Symptoms- What a patients shows

Question 10

Framework of pathophysiology: terms and concepts:
What are the definitions of idiopathic, nocosomial, iatrogenic and multifactorial?

Answer 10

1. Idiopathic- Unsure of cause
2. Nosocomial- Healthcare-associated infections (HAI) e.g. MRSA
3. Iatrogenic- Caused by doctor/hcp by their words or actions
4. multifactorial- lots of causes

Question 11

The clinical course of a disease [biomedical perspective]

Answer 11

1. Exposure to pathogen
2. Biological onset of disease *
3. Symptoms appear *
4. Diagnosis **
5. Therapy begum **
6. ‘Outcome’ (cured, living w disease, deteriorated, died) **
   *pre-clinical phase
   **clinical phase

Question 12

Clinical manifestation:
Examples of
symptoms
signs
syndrome

Answer 12

Symptoms= Feeling: Headache, feeling hot, generally unwell

Signs= Measurable: Temperature >38.9, Inflammatory markers, low blood pressure, low platelet count
Syndrome= Toxic shock syndrome

How does the disease present?
consider if its local vs systemic OR acute vs chronic

Question 13

What are some inflammatory markers for influenza? (signs + symptoms)

Answer 13

A sudden high temperature
Tiredness and weakness
Headache
General aches and pains
A dry, chesty cough
Sore throat
Difficulty sleeping
Loss of appetite
Diarrhoea or tummy pain
Feeling sick and being sick
Chills
Runny or blocked nose
Sneezing

Question 14

What are some inflammatory markers for E. coli O157 infection?

Answer 14

Diarrhoea
Stomach cramps
Occasionally fever
About half of people with the infection will have bloody diarrhoea.
A small number of people with E. coli O157 infection go on haemolytic uraemic syndrome (HUS)
Some people become infected but don’t develop symptoms.

Question 15

What are some inflammatory markers for
Staphylococcus aureus?

Answer 15

A painful red lump or bump on the skin (boil or carbuncle or even abscesses)
Hot, red and swollen skin (cellulitis)
Sores, crusts or blisters (impetigo)
Sore, red eyelids or eyes (stye or conjunctivitis)
Staph bacteria can also cause more serious infections, like blood poisoning and toxic shock syndrome. These are much less common than skin infections.

Question 16

THREE Systemic Effects of Infection?

Answer 16

1. Fever: or pyrexia, is the elevation of an individual’s core body temperature above a ‘set-point’ regulated by the body’s thermoregulatory centre in the hypothalamus.
2. Sepsis: A severe systemic response to infection, characterised by widespread inflammation and organ dysfunction.
3. Organ dysfunction

Question 17

Fever as a systemic effect of infection:

Answer 17

Fever: or pyrexia, is the elevation of an individual’s core body temperature above a ‘set-point’ regulated by the body’s thermoregulatory centre in the hypothalamus.

Elevated body temperature >38°C in response to infection, caused by the release of pyrogens:
* Physiological process brought about by infectious causes or non-infectious causes such as inflammation, malignancy, or autoimmune processes.
* Fever is mediated by the pyrogenic activity of prostaglandins (pgs), specifically pge2.
* Peg2 stimulate endogenous pyrogens such as il-1, il-6, tumour necrosis factor (tnf), and interferon (ifn) to alter the hypothalamic set point
* Endogenous pyrogens also act to trigger an immune and inflammatory response. The immune response includes leukocytosis, T cell activation, B cell proliferation, NK cell killing, and increased white blood cell adhesion.
* The inflammatory response includes increased acute phase reactants, increased muscle protein breakdown, and increased synthesis of collagen.

Question 18

Sepsis as a systemic effect of infection:

Answer 18

A severe systemic response to infection, characterised by widespread inflammation and organ dysfunction.

• Infection triggers a dysregulated immune response, leading to a systemic inflammatory state.
• Release of pro-inflammatory cytokines causes widespread endothelial dysfunction, coagulation abnormalities, and organ dysfunction.
• Understanding the cascade of events is crucial for early recognition and management of sepsis.

…Sepsisprogressing to septic shock and multi-organ failure results from
Circulatory insufficiency characterised by hypovolemia
Myocardial depression
Increased metabolic demands
Vasoregulatory perfusion abnormalities

Question 19

Organ dysfunction as a systemic effect of infection:

Answer 19

Infections can directly impact various organs, leading to impaired function or failure.

• Organ dysfunction is an integral part of sepsis, and the presence of unexplained organ dysfunction in a patient who is acutely ill should raise suspicion of the possible presence of sepsis and encourage an appropriate diagnostic examination.
• The pathophysiology of organ dysfunction in sepsis is similar for all organs and involves complex haemodynamic and cellular mechanisms.
• The first goal in the prevention of organ dysfunction in sepsis is to restore and maintain adequate oxygen delivery to cells.
• Single-organ dysfunction in sepsis is rare, and several organs are usually affected; mortality in patients with sepsis correlates with the number of organs that are affected.
• Most organ dysfunction in sepsis is reversible.
• Current treatment for sepsis aims to limit the development of organ dysfunction by providing rapid control of infection, haemodynamic stabilization and organ support when possible to ensure recovery of organ function.