Practical 2: Inflammation and tissue repair

Question 1

Which of the symptoms listed below is NOT a symptom of an acute inflammation?

a. Calor
b. Turgor
c. Dolor
d. Tumour

Answer 1

b. Turgor

Question 2

An inflammatory reaction consists of two components. Which ones?

a. a vascular reaction and a humoral reaction
b. a humoral reaction and a cellular reaction
c. a neuronal reaction and a vascular reaction
d. a vascular reaction and a cellular reaction

Answer 2

d. a vascular reaction and a cellular reaction

Question 3

Toll-like receptors are activated by:

a. Bacterial and viral molecules
b. Interleukings like IL-1 and IL-6
c. Histamine
d. Endothelial selectins

Answer 3

a. Bacterial and viral molecules

Question 4

Which effect does histamine exert on venules?

a. vasoconstriction leading to capillary congestion
b. local activation of eotaxin
c. serotin release from vascular endothelium
d. increased permeability of the vascular wall

Answer 4

d. increased permeability of the vascular wall

Question 5

Where does leukocyte migration through the vessel wall take place during an acute inflammation reaction?

a. arterioles
b. capillaries
c. venules
d. lymph vessels

Answer 5

c. venules

Question 6

Which description of blood circulation in a focus of acute inflammation is INCORRECT?

a. hydrostatic pressure decreases, resulting in congestion
b. vascular leakage leads to an increased blood viscosity
c. blood congestion enhances margination of leucocytes
d. vascular leakage can be the direct consequence of epithelial damage

Answer 6

a. hydrostatic pressure decreases, resulting in congestion

Question 7

Selectins mediate the linkage of

a. leukocytes to components of the extracullar matrix
b. chemokines to chemokine receptors
c. leukocytes to endothelial cells
d. endotheliial cells to fibrinous polymers

Answer 7

c. leukocytes to endothelial cells

Question 8

The ‘pavementing’ of vascular endothelium by leukocytes during inflammatory reactions is mainly mediated by linkage of

a. integrins to VCAM-1 or ICAM-1 of the endothelial cell
b. selectings to CD31 of the leukocyte
c. CD31 to leukocyte selectins
d. CD31 of the leukocyte to CD31 of the endothelial cell

Answer 8

a. integrins to VCAM-1 or ICAM-1 of the endothelial cell

Question 9

Chemotaxis is best described as:

a. uncoordinated cell migration in the extravascular compartment
b. coordinated cell migration through a concentration gradient
c. secretion of interleukins bij inflammatory cells
d. fixation (immobilisation) of inflammatory cells at an inflammatory site

Answer 9

b. coordinated cell migration through a concentration gradient

Question 10

Which of the following substances plays an important role in chemotaxis?

a. C5b and TNF
b. P-selectin and CD-31
c. Toll-like receptors and CD-14
d. C5a and leukotriene B4 (LTB4)

Answer 10

d. C5a and leukotriene B4 (LTB4)

Question 11

As you know, there are several important connections between an acute inflammatory reaction on one hand, and haemostasis and fibrinolysis on the other. Which substance does not only cause fibrinolysis, but also splicing of complement factor C3 and activation of Hageman factor?

a. thrombin
b. plasmin
c. bradykinin
d. bradykinine

Answer 11

b. plasmin

Question 12

Microorganism opsonisation by designated proteins (opsonins) precipate:

a. apoptosis of infected cells
b. activation of the membrane attack complex (MAC)
c. contration of capillary endothelial cells
d. phagocytosis of microorganisms

Answer 12

d. phagocytosis of microorganisms

Question 13

A chronic inflammation is characterised by the activity of:

a. basophils
b. neutrophils
c. mast cells
d. macrophages

Answer 13

d. macrophages

Question 14

The two main components of granulation tissue are:

a. endothelium and granulocytes
b. endothelium and fibroblasts
c. fibroblasts and collagen
d. collagen and granulocytes

Answer 14

b. endothelium and fibroblasts

??? we don’t understand???

Question 15

Make sure you can identify cellular components that are discussed in the practical

Answer 15

and also the abnormalities…

e. g.
- Mucosa
- Muscularis mucosae
- Submucosa
- Muscularis propria (the inner circular layer, and the outer longitudinal layer)
- Serosa
- Meso-appendix
- Surface epithelium
- Crypts
- Goblet cells
- Lymph follicles
- Lymphocytes
- Plasma cell

Question 16

We first assess a microscope slide showing the image of a normal appendix, obtained from a 50 year old man whose appendix was removed during laparotomy due to anastomotic leakage. This microscope slide indicates that is appendix was indeed normal.

Why did the surgeon remove this appendix?

Answer 16

He was already performing a laparotomy: removing an appendix does not lead to an increased post operational morbidity and it eliminates the chances of developing appendicitis.

Question 17

An important aspect of surgery is to assess and decide about a surgical indication. Which surgeon has made the best surgical decision?

1. The surgeon who always turns out to be right when he performs an appendectomy (i.e. the appendix is always inflamed)
2. The surgeon who is sometimes wrong (the appendix turns out to be normal upon surgery)

Answer 17

The second surgeon, the one who is sometimes wrong, makes optimal surgical decisions. The first surgeon does not operate until there is no doubt about appendicitis, otherwise he would also be wrong in some cases. This means that the cases of doubt are left untreated, with chances of developing complications. It is better to remove a healthy appendix regularly, than to leave an acutely inflamed appendix in place sporadically.

Question 18

What will a surgeon during an appendectomy do when he sees that the appendix is NOT inflamed?

a. Leave the appendix in situ, close the wound and conclude surgery.
b. Remove the appendix anyway.

Answer 18

He or she will remove the appendix regardless of its condition. The logic behind this is the same as in the 50 year old patient from the first microscope slide: removing an appendix, once surgery has already begun, does not result in an increase of post operational morbidity and it eliminates the chances of developing a later appendicitis.

Question 19

Not performing an appendectomy…

Why is it considered a serious mistake when a surgeon does not perform an appendectomy in the case of acute appendicitis?

Which complication is feared most, and what are its acute risks and long-term sequelae?

Answer 19

Rupture, causing the infected appendix’ content to be released into the peritoneal cavity. This causes a localised peritonitis when the peritoneum adheres to the surrounding structures and the greater omentum, causing the infected area to be confined to a limited space. Rupture can secondly cause a generalised peritonitis when the infection is not confined and able to disseminate in the peritoneal cavity. Especially the generalised peritonitis poses a serious threat for a patient’s health.

Long-term sequelae are caused by a more fibrinous inflammation: This gives rise to fibrotic adhesions that impede the passage of nutrients and faeces through the bowel, as well as causing abdominal pains. When such a patient has to undergo abdominal surgery again, adhesions of the bowel will make an operation more complicated.

Question 20

In some blood vessels, leukocytes can be seen adhering to the endothelium. This is an early step of an acute inflammatory reaction. Look at the image for a magnification of this slide.

Why are these leucocytes present? The appendix is not inflamed, or is it?

Answer 20

Surgically manipulating the appendix activates its endothelium, causing leucocyte adhesion to endothelium.

It is rumoured that in appendectomies where the appendix turned out to be healthy, surgeons manipulated the appendix for an extended period of time. They would cause a mechanically induced inflammation, proving them right in their surgical decision for appendectomy…

Question 21

We will now evaluate a microscope slide of the appendix obtained during appendectomy of a 15 year old boy, who had been ill for 1 day, with a nagging abdominal pain. In the course of hours, the pain increased.

At first, the pain was localised around the navel diffusely, but it had slowly moved to the bottom right side of his stomach.

The boy was rushed to the hospital by his GP who suspected him from acute appendicitis.

Answer 21

.

Question 22

Place the following stages of acute appendicitis in the correct order:

• Luminal occlusion by a faecaloma for instance
• Increase of intraluminal pressure and pressure on the appendicular wall
• Obstruction of the venous return
• Ischemia of the mucosa
• Invasion of the appendicular wall by bacteria
• Acute inflammatory reaction
• Ulceration and necrosis of cells in the appendiceal wall
• Rupture of the appendix
• Peritonitis

Answer 22

Dit is al goeie volgorde, eerst ff random zetten?

Question 23

Why is a severely inflamed appendicular wall prone to ruptures?

What causes the weakening of the appendicular wall?

Answer 23

A multitude of activated neutrophils infiltrate the appendicular wall tissue, secreting neutral proteases that mediate matrix breakdown (which enables neutrophils through tissues), before releasing phagolysosomes with toxic substances when they (neutrophils) die. Tissue damage and degradation weakens the appendicular wall. During a severe inflammation, this can even cause an abscess.

Question 24

How would you describe an area characterized by inflammatory cell decay, as a result of which a cavity arises filled with inflammatory cells and cell debris?

a. Ulcer
b. Phlegmon
c. Abscess
d. Empyema

Answer 24

c. Abscess

(such as cavity is called an ‘abscess’. the liquid, turbin content of an abcess consists of cell remnants and inflammatory cells)

Question 25

Myeloperoxidase brings about the

a. Activation of macrophage’s lysosomal proteases
b. Recruiting of young white blood cells from bone marrow to the body’s circulation
c. killing of microorganisms in the phagolysosome of a neutrophil
d. attraction of inflammatory cells to an inflammatory focus

Answer 25

c. killing of microorganisms in the phagolysosome of a neutrophil

Question 26

The most effective and powerful method of killing bacteria in neutrophils is mediated by

a. binding of the membrane-attack complex (MAC)
b. induction of apoptosis
c. acidic hydrolases
d. the H2O2-MPO-halide system

Answer 26

d. the H2O2-MPO-halide system

Question 27

A fibrinous inflammatory process is characterised by

a. formation of fibrous (scar) tissue
b. formation of tissue defects
a. a serous excrete in the extravascular compartment
d. profuse formation of fibrin in the extravascular compartment

Answer 27

d. profuse formation of fibrin in the extravascular compartment

Question 28

The phage of resolution in the process when an inflammation

a. disappears completely, without remainders;
b. disappears, leaving scar tissue behind
c. transforms into a chronic inflammation
d. disappears, leaving behind an air-filled cavity

Answer 28

a. disappears completely, without remainders;

Question 29

What is the correct definition of an ulcer?

a. a purulent focus in a solid organ
b. an epithelial defect, caused by inflammatory damage
c. a defect in the continuity of skin or mucosa
d. an area of nectrotic tissue

Answer 29

b. an epithelial defect, caused by inflammatory damage

Question 30

Several abdominal disorders can present itself in a way that is interpreted preoperative as an acute appendicitis: These are, amongst others, gastro-enteritis (caused by Yersinia and other infections), acute cholecystitis, and urinary tract infections.
A young woman presenting with pain in the lower right part of her abdomen has a broader differential diagnoses than a man with similar symptoms.

The diagnosis of acute appendicitis is therefore more frequently rejected in women than in men (1 out of 3 women versus 1 out of 7 men).

Devise three diagnoses which you should consider with a woman, but not with a man.

Answer 30

Salpingitis; ectopic gravidity, endometriosis

Question 31

Isn’t it unbelievable that a diffuse and cell-rich acute inflammation does not induce severe destruction of the delicate alveolar parenchyma? After all, the seemingly more robust appendicular wall is often destroyed during an inflammation!

In clinical practice however, a bronchopneumonia turns out to heal without long-term damage.

Obviously, a strong selective pressure can be seen for those characteristics that protect the lung from permanent damage upon infection: The lung is an indispensable organ that is prone to infections.

The likelihood of tissue damage depends on the pathogen that causes the infection. A feared pathogen is Staphylococcus aureus, for a lung infection with this bacterium can indeed cause tissue destruction and create an abscess.

Answer 31

A remark….

Question 32

Some inflammatory processes of the lung, of which have the aetiology remains unclear, occur primarily in the interstitium of the lung, instead of in the air-filled space. Some of these diseases induce severe damaging of the delicate pulmonary architecture, mainly by inflammatory lung fibrosis.

Cryptogenic fibrosing alveolitis (idiopathic pulmonary fibrosis)

An infamous example is the so-called cryptogenic fribosing alveolitis (The Americans call it ‘usual interstitial pneumonia’), to which a clinician often refers as ‘idiopathic pulmonary fibrosis’. This disease is characterised by focal inflammatory progressive interstitial fibrosis, causing lung tissue to become functionally impaired.

Answer 32

You clearly see in the picture lots of fibrotic tissue with fibroblasts, the thin layer of the alveoli is not at all visible

Question 33

How can you distinguish this wound from a fresh wound (say, younger than one hour)?

Answer 33

The wound is covered with dried-in crusta composed of fibrin and cell remnants. Inferior to the wound, granulation tissue is starting to form.

Question 34

In tissue adjacent to the ulcus, you can find mitotic figures.
Which cell types are proliferating here?

Answer 34

(myo-) fibroblasts, endothelial cells, and perhaps some macrophages.

Question 35

Vascular endothelial cells close to the ulcer are enlarged and lay closer to each other than vascular endothelial cells distant from the ulcer.
Can you name the right terminology for these two endothelial changes?

Answer 35

Hypertrophy and Hyperplasia of the endothelium.

Question 36

Compared to the previous slide, this slide shows a widened dermis.

Is this skin hypertrophic?
Or was the previous skin sample atrophic?
Or are both skins neither hypertrophic nor atrophic, and if so, can you give an explanation?

Answer 36

This excision was made on the back. The dermis of the back is wider than the abdominal dermis. The skin’s microanatomy differs for each location.

An experienced microscopist can easily separate the skin of the sole of one’s foot from the skin of the back, the abdomen, the face, the scalp, etc.

Question 37

Compare the scar tissue to the adjacent normal dermis (and, if possible, to the subcutis).

Can you name the essential differences?

Keep in mind the following parameters:

• Aspect of the extracellular matrix (compare the collagen in scar tissue to that of the neighbouring reticular dermis)
• Richness in cells
• Vascularisation
• Aspect of the fibroblasts
• The presence of a lymphocytic infiltrate.

Answer 37

• The aspect of the extracellular matrix is pale with frail fibres. The wide collagenous bundles of normal reticular dermis are yet to be formed by remodelling of the scar matrix.
• There is an increased richness in cells
• Vascularisation is also increased, especially the capillaries.
• Fibroblasts are hypertrophic: these cells are actively producing matrix
• You can see several focal lymphocytic infiltrates.

Question 38

In one place you might have seen these two multinucleated macrophages (giant cells) that carry ‘something’ in their cytoplasm. Inspect this image.

What would these macrophages carry in their cytoplasm?

Answer 38

Remnants of surgical sutures. Macrophages try to remove this corpus alienum (plural: corpora aliena) by phagocytosis.

Question 39

At a distance from the scar of the surgical wound, the skin shows another little superficial scar area. Can you explain this second scar?

Answer 39

Sutures (on the left) and staple sutures (on the right) also cause trauma and therefore little scars.

Question 40

Characteristic of secondary wound healing is:

a. wound contraction
b. the formation of a small scar
c. the absence of an inflammatory reaction
d. the absence of collagen formation

Answer 40

a. wound contraction

Question 41

Which cells are responsible for wound contraction?

a. Myoepithelium
b. Myofibroblasts
c. Smooth muscle fibre
d. Macrophages

Answer 41

b. Myofibroblasts

Question 42

The difference between a hypertrophic scar and keloid is that

a. with keloid, there is no regression
b. keloid only occurs in darker skin types
c. with keloid, more collagen is created
d. keloid only occurs with burn scars

Answer 42

a. with keloid, there is no regression

Question 43

What is, most likely, the direct cause of his oesophageal varices?

a. Ascites
b. Diaphragmatic hernia
c. Portal hypertension
d. Chronic reflux

Answer 43

c. Portal hypertension

Question 44

Name two findings that indicate portosystemic shunting caused by portal hypertension.

Answer 44

Haemorrhoids and periumbilical caput Medusae.

Question 45

Name the probable direct cause of portal hypertension.

a. right-sided heart failure
b. obstruction of the hepatic venous return
c. pulmonary hypertension
d. liver cirrhosis

Answer 45

Liver cirrhoses.

Although all other options might induce portal hypertension, the anamnestic finding of alcohol above leaves liver cirrhosis caused by chronic toxic liver damage as the most likely option

Question 46

Select the essential terminology concerning the pathogenesis of liver cirrhosis:

a. fibrosis and regeneration
b. necrosis and apoptosis
c. inflammation and recovery
d. stuwing en drukatrofie

Answer 46

a. fibrosis and regeneration.

this leads to the formation of nodules of regenerating liver tissue with a deviant architecture

Question 47

Why does liver cirrhosis lead to portal hypertension?

Answer 47

The normal liver lobulus is a low-pressure system. It receives venous blood from the portal system, which is then conducted by the lobular sinuses to the central vein, from where blood is transported to the hepatic vein and the vena cava. The pressure drops only slightly. Disruptions in the lobular architecture will soon lead to an increase in resistance, causing an upstream rise in pressure in the portal vein (because of the downstream obstruction).

Question 48

Liver cirrhosis is an important cause of ascites.

Name 2 factors that cause ascites.

Answer 48

• Portal hypertension, leading to an increased capillary pressure in the splanchnic system causing liquids to leave the vascular compartment.
• Hypoalbuminemia due to liver failure, leading to a decreased oncotic pressure of the vascular compartment.

Question 49

To determine whether a patient with chronic liver damage has already developed cirrhosis, a liver biopsy has to be made. Before the clinician decides to take such a biopsy, he checks the patient for normal blood coagulation.

Give two arguments why this is important when a biopsy is taken from a patient with liver disease.

Answer 49

1. Coagulation factors are synthesized in the liver. Liver disease may lead to a deficiency in these factors, raising the chances of a severe bleeding (haemorrhagic diathesis).
2. The biopsy wound caused by the (needle) biopsy is not plugged by surrounding tissues. This allows blood to flow freely into the abdominal cavity, especially when blood coagulation does not occur.

Question 50

What are the most important causes for liver cirrhosis?

Answer 50

• Alcoholic liver disease (60-70%)
• Viral hepatitis (10%)
• Disease of the biliary system (5-10 %)
• Cryptogenic (10-15 %)

Question 51

What is the essential difference between liver fibrosis and liver cirrhosis?

Answer 51

With liver cirrhosis, numerous regenerative noduli are formed. This irreversibly damages the liver’s architecture, leading to portal hypertension and liver failure. In the case of isolated fibrosis (liver fibrosis), this architectural disruption has not yet occurred.

Question 52

In these samples, many hepatocytes harbour spaces that are optically empty.

1. How is this called?
2. Describe the underlying process.
3. What causes this process?

Answer 52

1. Steatosis
2. Accumulation of lipids in the hepatocyte
3. A disruption of fatty acid metabolism secondary to toxic damage to the hepatocyte.

Question 53

What are the three most important mechanisms by which liver cirrhosis causes death?

Answer 53

1. Liver failure
2. Portal hypertension
3. Hepatocellular carcinoma