WOUND HEALING AND SEPSIS PAS 215

2022
By

PROF. EDMUND MUONIR DER

MBChB, MGCPs, FWACP

Pathologist

HOD OF PATHOLOGY

SOM-UDS
The wound
• Necrosis leads to loss of tissue and the development of a wound.
• Wounds are divided into two:
• 1. close wound: Contusion caused by blunt injury.
• 2. Open wound:
a. Abrasion
b. Laceration
c. Penetrating
d. Perforation
e. Avulsion; partial and complete.
• Wounds can also be divided into clear and infected wounds.
 The wound
• Features to consider when describing a wound:
• 1. Location (site)
• 2. Size
• 3. Shape
• 4. Support
• 5. Edge
• 6. Depth
• 7. Floor
• 8. Base
• 9. Colour
• 10. Infection
• 11. others
 Wound Healing

1. Healing by primary intention

2. Healing by secondary intention

 Healing by primary intention

• Features:
Clean surgical wounds
Minor wounds
Approximation of wound edges by sutures
Less scar formation
Less contraction of the scar
 1.Primary Intention: STEPS

• Day 1:
Fibrin clot (haematoma) develops.
Neutrophils infiltrate the wound margins.
There is increased mitotic activity of basal cells of squamous epithelium in the
apposing wound margins.
• Day 2:
Squamous cells from apposing basal cell layers migrate under the fibrin clot and
seal off the wound after 48 hours.
Macrophages emigrate into the wound.
 1.Primary Intention: STEPS
• Day 3:
Granulation tissue begins to form.
Initial deposition of type III collagen begins.
Macrophages replace neutrophils.
• Days 4-6:
Granulation tissue formation peaks
Collagen bridges the incision site.
 1.Primary Intention: STEPS

• Week 2:
Collagen compresses blood vessels in fibrous tissue, resulting in
reduced blood flow.
Tensile strength is ∼10%.
• 1st month:
• Collagenase remodeling of the wound occurs.
• There is replacement of type III collagen by type I collagen.
 1.Primary Intention: STEPS
• 1st to 3rd month:

Tensile strength increases, reaching ∼80% .

Formation of a scar

Scar tissue is devoid of adnexal structures (e.g., hair, sweat glands)

and inflammatory cells.
 2. Secondary Intention

• Features:

 Wound remains open.

 Used for gaping or infected wounds.

 More intense inflammatory reaction than primary healing.

 Increased amount of granulation tissue formation than in primary healing.

 Wound contraction caused by increased numbers of myofibroblasts.

 Factors that impair wound healing

These are divided into:

a. Local factors

b. Systemic factors
Factors that impair healing
a. Local factors
1. Persistent infections: Staphylococcus aureus is the most common
pathogen.
2. Foreign objects: suture, needles, pieces of bone, cellular debri,
gauze, metals, etc
3. Increased mobility of the affected site
4. Others
 Factors that impair healing
b. Systemic factors
1.Metabolic disorders
• Example-diabetes mellitus increases susceptibility to infection by decreasing
blood flow to tissue and increasing tissue levels of glucose.
2. Glucocorticoids
• Interfere with collagen formation and decrease tensile strength
• Occasionally used along with antibiotics to prevent scar formation (e.g.,
bacterial meningitis)
3. Immunosuppression
4. Ischaemia and anaemia
 Factors that impair healing
• 5. Nutritional deficiencies
• Decreased protein (e.g., malnutrition)
• Vitamin C deficiency
• Decreased hydroxylation of proline and lysine causes decreased tensile strength in
collagen owing to loss of linkage sites between α-chains.
• Trace metal deficiency
• Copper deficiency leads to decreased cross-linking of α-chains in collagen.
• Zinc deficiency leads to defects in removal of type III collagen in wound remodeling.
 Keloid formation
The raised scars caused by
excessive synthesis of type III
collagen.
Common in African Americans
May occur as the result of third-
degree burns.
Lesion extends more than the
original size of the wound
• The End
 Sepsis
By
Prof. Edmund Muonir Der
MBChB, MGCPS, FWACP
HOD OF PATH
SOM-UDS
 Sepsis
• Introduction:

• Sepsis remains a critical problem with significant morbidity and

mortality even in the modern era of critical health care management.

• Multiple organs and systems derangements exist in sepsis.

• Septic patients have substantial, life-threatening alterations

particularly in their coagulation system.
 Some Definitions
• Bacteraemia:
• The transient presence of small numbers of non-proliferating
bacteria in the blood
• Usually asymptomatic
• Entry points: inflammation, oral, trauma, haematogenous etc

19
 Some Definitions

• Systemic Inflammatory Response Syndrome:

Defined in 1992 as:
fever >38°C or hypothermia <36°C

tachycardia >90/min

tachypnoea >24/min or PaCO2 <32 mm Hg

WBC >12x109/L or <4x109/L

20
 Some Definitions
• Sepsis:
Infection + SIRS

• Septicaemia
Proliferating bacteraemia resulting in sepsis

21
 Risk Factors of sepsis

 chronic disease
 burns
 prior antimicrobial treatment
 invasive procedures
 age (neonates, elderly)
 immunosuppression
 Genetics

22
Aetiology: Community Acquired.
Depends on the point of entry:

S. pneunomiae, N.meningitidis,
Pneumonia
Resp
Meningitis
S. pyogenes, M. cat., aerobic GNRs, etc
Fungi: aspergillosis,

Wounds, S. aureus, St. pyogenes, other GPCs

Skin
burns Anaerobes

Urinary
Tract
Pyelonephritis Aerobic GNRs

Cholangitis Enterococcus faecalis, coliforms,

Bowel
Peritonitis B.fragilis, Salmonellae, S.typhi

Pelvic Endo-metritis N.gonorrhoeae, anaerobes

23
Aetiology: Hospitalised patients
Urine Coliforms (E. coli, proteus etc) Nosocomial: Enterobacter,
catheter Pseudomonas
Usually GPC eg S. aureus, epidermidis;
IV catheter
Enterobacter, Pseudomonas, Acinetobacter, C. albicans
Pseudomonas, Enterobacter, Klebsiella, S. aureus (50%
Intubation
polymicrobial

Post-op S. aureus, E.coli, anaerobes (clostridium),

Post-splen S. pneumoniae, H influenzae, N.meningitidis.

(ascites) enteric aerobic GNR e.g. E. Coli, Klebsiella,

Bowel
perforation) coliforms, B. Fragilis (polymicrobial)

Burns GPC, Pseudomonas, C. Albicans

Immune Any
24
Pathophysiology – Outstanding Questions
Are septic patients hyperinflammatory or
immunocompromised?
What ‘magic bullet’ can improve survival?
What are the cellular alterations responsible for
organ injury?
Why do the patients die?

25
 Outcomes

• Sepsis

 Severe Sepsis: sepsis with dysfunction of a

least one organ or organ system.
• →sepsis + MSOF

• Septic Shock:
sepsis + refractory hypotension

26
 STAGING OF SEPSIS
• The International Sepsis Definitions Conference in 2001 modified the
model of SIRS and developed an expanded view of sepsis.
• Based on four separate characteristics designated by the acronym
PIRO.
 STAGING OF SEPSIS
• P: stands for the predisposition, indicating pre-existing co-morbid
conditions that would reduce survival.
• I: is the insult or infection, which reflects the clinical knowledge that
some pathogenic organisms are more lethal than others.
• R: represents the response to the infectious challenge, including the
development of SIRS.
• O: stands for organ dysfunction and includes organ failure as well as
the failure of a system such as the coagulation system.
 Clinical Manifestations
1. SIRS symptoms
2. Skin lesions
3. Mental changes
4. Raised intracranial pressure: headache, vomiting
and papilloedema
5. Complications e.g.
 Hypotension (shock)
 Thrombocytopenia and Bleeding (DIC)
 Leukopenia
 End organ failure (hypoxemia, acidosis,
oliguria, jaundice, heart failure)
29
 Investigations
 Cultures (Blood, Sputum, Urine, etc)
 ! Skin sepsis
 Blood Cultures: peripheral + access devices
 Imaging + Drainage
 Nonspecific markers: CRP, ?IL6

30
 Prompt Antibiotic Therapy
Gram Skin, Abscess, gentamicin, vancomycin, penicillin,
Positives Endocarditis clindamycin

Pseudo- Neutropenia, ceftazidime, aminoglycoside,

monas nosocomial, meropenem, ciprofloxacin, ticarcillin

CAP Mycoplasma, Macrolide

chlamydia

GNRs UTI, nosocomial, Cefotaxime/ceftriaxone,

fluoroquinolone, aminoglycoside
Anaerobes Fasciitis, bowel Metronidazole, clindamycin

Capsulated Meningitis, skin Ceftriaxone, penicillin

findings,
Meningo Meningitis, Ceftriaxone
purpura/petechiae
HIV … septrin
31
 Supportive Therapy
 Prompt Source control
-Lung-protective Ventilation
 Fluid therapy and vasopressors
 Glucose Control with insulin
 Activated protein C
 Steroids
 DVT prophylaxis
 Transfusion (decrease threshold); no
FFPs,
 Sedation and Analgesia
 Stress ulcer prophylaxis
 Dialysis
32
Prevention

 Good Hygiene/handwashing

 Prompt treatment of local infections

33
References
Bone RC. Gram-Negative Sepsis: a Dilemma of Modern Medicine. Clin
Micr Rev 1993, 6(1):57-68

Remick DG. Pathophysiology of Sepsis. Am J of Path 2007, 170 (5):

1435-1444

Hotchkiss RS, Karl IE. The Pathophysiology and Treatment of Sepsis. N

Engl J Med 2003, 348:138-150

Lisboa T, Diaz E et al. The Ventilator-Associated Pneumonia PIRO Score.

Chest. 2008.134 (6) 1208-1216

Twum-Danso K. Tutorial Session

34
 References

• The Global Incidence of

• Puerperal Sepsis
• Protocol for a Systematic Review
• Dr MC Chisembele
• Tutor: Dr L Say
• WHO/GFMER/IAMANEH
• Postgraduate Training Course in Reproductive
• THE END