Sepsis Flashcards

1
Q

5 examples of relevance… GO

A

1- Estimated to affect more the 30 million people worldwide 🌎 each year.
2- Every 4 hours someone in the UK dies of sepsis
3- 1 in 10 deaths associated with pregnancy and childbirth is due to sepsis.
4- 11 million people a year will die from sepsis.
5- 1 in 4 NHS trusts is failing to give antibiotics to half of their patients with sepsis within the recommended time.

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2
Q

Who is at risk form developing sepsis?

A

Anyone affected by an infection can progress to sepsis conditions but some vulnerable groups are at a higher risk. These include:

  • Elderly 🧓
  • Pregnant women
  • Neonates
  • Hospitalised patients
  • People with HIV/ aids, liver cirrhosis, cancer, kidney disease and autoimmune diseases
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3
Q

What are the 4 causes of sepsis. Identify the main cause.

A
  • Bacteria 🦠- causes 60% of all cases
  • Viruses
  • Parasites
  • Fungi
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4
Q

4 fats about bacteria….GO

A

1- Single called organisms
2- Can exist in environments with or without O2
3- Can absorb nutrients from the host
4- Can replicate themselves with binary fission- requiring protein synthesis

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5
Q

What is Binary Fission?

A

Division from a single entity into 2 or more

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6
Q

Explain the 4 step process of binary fission…. GO

A

1- DNA 🧬 replication
2- Cell wall and membrane will invaginate (fold in on itself)
3- Invagination complete
4- Cells separate

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7
Q

What is a gram positive bacteria?

A
  • A gram positive bacteria has a thick cell wall

- During a gram stain test it will be stained purple by the dye.

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8
Q

What is gram negative bacteria?

A
  • A gram negative bacteria has a thin cell wall.

- During the gram stain test it will not be stained by the dye.

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9
Q

What are endotoxins?

A
  • These are structural components of the bacterial cell wall.
  • They are freed from the outer membrane of the bacteria when they are destroyed by the immune system
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10
Q

Endotoxins stimulate the release if 10 things.

Can you name five of them….GO

A
1- Tumour necrosis factor 
2- Activation of the coagulation system 
3- Prostaglandin, thromboxane, leukotrienes and prostacyclin release
4- Beta- endorphins 
5- Bradykinin
6- Oxygen- derived free radicals 
7- Platelet activating factor
8- Anaphylatoxins (C5a and C3a)
9- Myocardial depressant factor 
10- Interleukin 1 and 2
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11
Q

What is an Exotoxin?

A
  • These are products of microorganisms that are harmful to the host.
  • Some bacteria 1 specific toxin to cause disease
  • for example Tetanus, Diphtheria and streptococcus
  • Another group of bacteria harms the host through actions of both endo and exo toxins.
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12
Q

What is the difference between endotoxins and exotoxins?

A

Endotoxins..

Are the lipid portion if the lipopolysaccharides (LPSs) that are part of the outer membrane of the cell wall of gram negative bacteria.
The endotoxins are freed when the bacteria die and the cell wall breaks apart.

Exotoxins

Are proteins inside the pathogenic bacteria, most commonly found in gram positive bacteria.
They are secreted/ released into the the surrounding medium following lysis.

Both substances (endotoxin and exotoxin) stimulate the inflammatory cascade

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13
Q

The endotoxins and exotoxins cause human mediators to be released, what does this cause in the case of sepsis?

A
  • The human mediators released cause widespread vasodilation and increase the permeability of tissues.
  • These physical changes are caused by endo and exotoxins
  • Inflammation is a normal response but in sepsis and exaggerated, excessive inflammatory response is produced throughout the body.
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14
Q

What is a histamine?

A
  • These are found in mast and basophils cells.

- Histamines are a profound vasodilator and they increase cellular permeability.

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15
Q

What are kinins ?

A
  • These are rapidly generated in blood 🩸 plasma after a tissue injury, leading to vasodilation, increased vascular permeability and cell migration.
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16
Q

What are prostaglandins?

A
  • A potent hormone like substance found in most tissues- influences vascular tone, platelet aggregation and inflammatory response
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17
Q

How does sepsis develop?

A
  • Bacteria can gain entry to the host ie via an open wound.
  • Bacterial endotoxin binds to the CD14 macrophage receptor.
  • This stimulates white blood cells to release tumour necrosis factor
  • This stimulates other white blood cells to release other cytokines
  • Stimulates a massive inflammatory response
18
Q

What is the clinical effect of Tumour necrosis factor (TNF)

A
- Activates the inflammatory cascade 
Causes
- Fever 🥵 
- Hypotension (low BP)
- Tachycardia (fast heart rate)
- tachypnoea (fast resp rate) 
- Hyperglycaemia (Hugh glucose)
- Metabolic acidosis
19
Q

What is the clinical effect of interleukin 1?

A
  • Fever
  • Increased white blood cell count
  • Increase in amino acids produced by muscles
  • Decreased systematic vascular resistance
20
Q

What is the clinical effect of interleukin 6?

A
  • Fever
  • Antibody secretion
  • Neutrophil production
21
Q

What is the clinical effect of interleukin 8?

A
  • Stimulates neutrophil functions

- Attracts inflammatory cells to the site of infection/ injury

22
Q

What are the classic symptoms of Sepsis?

A
  • Temp higher the 38 or lower then 36
  • White blood cell count higher the 12000 mml or lower then 4000mml
  • Hypoxaemia - ( low O2)
  • Lactate higher then 4
  • Decreased urine operation
  • Hyperglycaemia(high blood sugar)
23
Q

The SEPSIS acronym helps diagnose sepsis.

Explain the acronym.

A
S= Slurred speech 🎤 
E= Extreme muscle pain 
P= Passing no urine
S= Severe breathlessness 
I= I feel I might die
S= Skin mottled or discoloured
24
Q

Please explain the physiology of Pyrexia (high temp)

A
  • Infection causes damaged cells
  • Damaged cells release pyrogens
  • Example of these pyrogens are Interleukin 1 and tumour necrosis factor (TNF)
  • Interleukin 1 and TNF act directly on the hypothalamus
  • They change the set point of the hypothalamus
  • The nervous system perceives the the person top be colder then normal.
  • Causing shivering
  • Temperature 🤒 increases
  • High temperature 🤒 is a classic symptom of Sepsis
25
Q

Explain the three things pyrexia (high temp) causes….GO

A

1- Releases of pyrogens
2- Direct action of cytokines
3- Increases metabolic rate —> the harder the organs work the more heat they generate.

26
Q

Pyrexia/ high temps cause cellular damage by ?

A
  • Damaging the Golgi Apparatus
  • Swelling the mitochondria
  • Changing the cellular permeability
  • Disrupting the nucleus and aggregation of chromatin which is a combination of DNA and proteins in the nucleus.
  • elevating protein synthesis.
  • High temps reduce the ATP (energy) production and you need ATP (energy) for normal electrical activity
27
Q

Sepsis can present as hypothermia as well as pyrexia why is this?

A
  • Organs may shut down

- Liver isn’t as well perfused so doesn’t produce as much heat

28
Q

Please explain the physiology of an increased heart rate?

A
  • The sympathetic nervous 😬 system stimulates an increased release of adrenaline and noradrenaline from the adrenal medulla (this is the stress response)
  • This stimulates the heart to contract faster by as adrenaline and noradrenaline act upon the alpha and beta receptors of the heart
29
Q

Why does your heart rate go up when you BP falls?

A
  • Drop in BP
  • Baroreceptors monitor your BP levels and pick up on the drop in BP
  • Baroreceptors send impulses to the medulla oblongata
  • Medulla oblongata is connected to the heart ♥️ by the vegas nerve (release the break)
  • Heart rate increases in an attempt to move the reduced circulatory volume in your circulatory system round your body faster 💨.
30
Q

Why does your resp rate rise when you have sepsis ?

A
  • Fall in Ph ( due to rising hydrogen levels)
  • Chemoreceptors in the cardiovascular 🫀 system detect this change
  • Chemoreceptors send impulses to the medulla oblongata
  • The medulla oblongata sends impulses to the Phrenic and respiratory nerves
  • This causes the resp rate to increase
31
Q

Why do the Ph levels fall in someone with sepsis?

A
  • Histamine makes the capillary and alveolar walls more permeable allowing liquid into the alveoli
  • Making it difficult to breath in O2
  • Causing cells to have to respire anaerobically leading to lactate and lactic acid production
  • This reduces the Ph eventually making someone acidotic
32
Q

What is lactate?

A
  • Lactate is the bi product of anaerobic respiration Anaerobic respiration is less efficient then aerobic respiration.
  • It creates a Ph imbalance
  • You produce lactate in situations of severe hypoxia
  • Lactate can also be produced and elevated due to hypotension, liver/ Kidney
    Dysfunction, anaerobic respiration, circulatory stasis and cell death ☠️.
33
Q

What is phagocytosis?

A

This is the process by which a cell (phagocyte) uses its plasma membrane to engulf a large particle such as a pathogen.

34
Q

What causes an elevated white cell (lymphocytes)count?

A
  • Lymphocytes develop as a young child 👶
  • They remain dormant until activation
  • The activation is called proliferation
  • The body only has a few lymphocytes that recognise invading organisms but thousands are needed to fight the infection.
  • When phagocytosis takes place a warning system is set up
  • Your body fights pathogens by remembering them and previously creating an antibody.
35
Q

How do antigens/ pathogens present themselves?

A
  • The phagocyte ‘eats’ or engulfs a bacteria
  • Parts of the bacteria (antigens) go to the surface of the phagocyte
  • The phagocyte presents the antigens to a T- helper cell
  • The T- helper cell is now activated.
  • when your immune system recognises a bacteria (that you have previously fought off)the T helper cell is activated and starts dividing. Increasing your white blood cell count
36
Q

What 4 inflammatory mediators are released in relation to sepsis?

A

1- Histamine- found in the mast and basophil cells. Histamine is a profound vasodilator
2- Kinins - are rapidly generated in the blood plasma after tissue injury leading to vasodilation, increased vascular permeability and cell migration.
3- Prostaglandins- A strong hormone like substance found in most tissues- influences vascular tone, platelet aggregation and inflammatory response
4- Cytokines - Protein, chemical messengers produces by damage tissue and white blood cells.

37
Q

Why does sepsis causes Hypotension (low BP)

A
  • Sepsis causes you to have a high temperature 🤒
  • High temperatures lead to dehydration
  • When you breath you breath out water
  • Meaning the faster you breath the more water you breath out the quicker you become dehydrated- dropping BP
  • Inflammatory mediators such as histamine cause wide spread vasodilation which can cause a drop in BP
38
Q

How can we explain confusion caused by sepsis?

A
  • The causes of mental abnormalities is not entirely understood,
    However some explanations may be:
  • cerebral hypo-perfusion—> inadequate blood flow to the brain
  • altered amino acid metabolism.
39
Q

Why may someone with sepsis present with elevated blood 🩸 glucose levels?

A
  • Sub optimal glucose levels are detected by glucagon releasing cells in the pancreas
  • Glucagon releasing cells of the pancreas are stimulated to release glucagon into the blood - target 🎯 organ the liver.
  • The liver breaks down the glycogen stores releasing glucose.

Normal glucose = 4.7

40
Q

Decreased urine output is a symptom of sepsis.

How do we explain a reduced urine output?

A
  • Low BP causes the renal system to stimulate an increase in renin secretion ( from the juxtaglomerular in the bowman capsule of the nephrons.
  • Renin converts angiotensin 1 to angiotensin 2
  • angiotensin 2 has two made effects, vasoconstriction of arteriolar smooth muscles and stimulation of aldosterone (hormone)secretion by the adrenal cortex.
  • Aldosterone increases the salt 🧂 and water 💦 concentration in the kidney decreasing the urine output.
  • The hypothalamus detects a change of decreased blood 🩸 volume or increased blood osmolarity.
  • This causes Anti diuretic hormone (ADH) to be released from the posterior pituitary gland in response to a decrease in BP ( detected by the baroreceptors)
  • ADH indirectly leads to an increased reabsorption of water and salt by the distal tubule, and the collecting ducts and the loop of henle in the nephron