number 12

Done by

Corrected by

Doctor موسى العبادي

Morphology of Granulomatous Inflammations

The first image (left) shows

a lung alveolus in which

necrosis is taking place. The

image below it shows the

alveolus at a higher

magnification and clearly

we can see the granuloma

(this alveolus represents a

necrosis center, it is called

a tubercle). The image on

the right shows a non-

necrotizing granuloma taken from the lymph-node, as we can see no tissue

damage is actually seen. The image below it shows the granuloma at a higher

magnification. The small blue image at the bottom-left corner shows the acid

fast stain which is used to detect the presence of the TB [the red color (which

the arrow is pointing to) indicates a positive result].

Dividing the granulomas into necrotizing and non-necrotizing is extremely

important for diagnosis for some diseases are more commonly associated with

one of the two types. For example, TB and fungal infections are common with

necrotizing granuloma while sarcoidosis (see last sheet) is more common in

non-necrotizing granulomas (of course you can find TB with non-necrotizing

granulomas and sarcoidosis with necrotizing granulomas (etc.), but this is rare).

*****necrosis tend to have infectious causes.

Side note: A special stain is used to diagnose TB called acid fast stain (also called Ziehl-Neelsen) and

fungal stains are used to detect fungi.

In some cases, the TB stain gives a negative result despite the presence of TB

(false negative) (small number of bacteria present; nothing was detected in the

section) still, clinically the doctor feels very suspicious and thinks that a TB is

present in this patient (due to symptoms for example), the more accurate tests

(PPD (purified protein derivative) test, quantiferon test, etc.) would need 4

weeks culturing tell the result is available. The doctor in this case gives the

patient “the benefit of doubt” and begins the TB treatment because if it was

really present and the treatment was given four weeks later things could

become more difficult (also if the type of mycobacterium is not known the

more accurate test would take a long time, the doctor can begin with a broad-

spectrum drug). To understand TB well read the last page “you can skip it”

The table below is of great importance

(the doctor talked a lot about it and at

least a question from this table seems

very likely in the mid-term). The cat

scratch disease is called so because cat

scratches cause it. Sarcoidosis is

diagnosed by exclusion, it can occur

anywhere in the body, but it is most

common in certain areas like the liver,

lungs, lymph nodes and skin. Sarcoidosis

is treated by giving steroids. Steroids are

not a desirable solution by patients (or

doctors) overall because it causes the

immunity of the patient to go down,

however, here it is the only solution as

they are very strong anti-inflammatory

molecules. This, however, tells us how important the diagnostic stage is.

Imagine you exclude TB and diagnose the disease as sarcoidosis despite the

presence of TB, then you would go on to give the patient steroids, guess what

will happen… You have actually made your patient’s immunity go down in the

presence of a very dangerous bacterium, this means that TB will go on to infect

the body very easily and cause serious complications to the patient and may

even kill them. Crohn disease is a chronic disease that is a member of a family

of diseases called the “inflammatory bowel diseases”. The etiology (cause) of

this disease is unknown, endoscopy is needed to diagnose the diseases. The

disease causes bloody diarrhea and in children it can cause troubles in their

growth. The inflammatory bowel diseases can be divided to two main

categories: Crohn disease and ulcerative colitis. The treatment is almost the

same for both despite different symptoms. In Crohn disease the ulcers formed

are superficial and do not exceed the lamina propria of the skin, but in the

ulcerative colitis the ulcers are deep and can extend from the surface to the

serous membrane. Granuloma is seen in both the diseases. Side note: there are several types of Crohn disease and their names often describe what problem they

cause. E.g. ileocolitis = the granuloma is in the ileum.

Systemic Effects of Inflammation

Any inflammatory response (acute or chronic) always brings about systemic

effects as the mediators travel in the blood to all over the body causing

different responses like fever. The most vital signs to notice are: temperature,

blood pressure, heart rate and respiratory effects.

The normal body temperature is (37.4-37.7°C) any increase above this range is

considered a fever, however, the fever can be a low grade one (e.g. 37.8°C,

often caused by viruses) or a high grade one (e.g. 41°C, often caused by

bacteria). Fever is also called “pyrexia” as it is caused by “pyrogens”, either

exogenous ones (lipopolysaccharides of bacteria, often cause high grade fever)

or endogenous ones (IL-1 and TNF, often cause low grade fever). All the

pyrogens induce the secretion of prostaglandin E2 increasing the body

temperature.

Acute phase proteins are produced by the liver (this is induced by mediators)

and secreted to the blood during an inflammation. For example, if the C-

reactive protein) CRP level is high in the blood we can tell that an acute

inflammation is present. Another test for inflammations is the erythrocyte

sedimentation rate (there is a constant rate in which the RBCs sediment in a

blood sample, in inflammations this rate changes).

Leukocytosis is the increase in the number of WBCs. This is a normal response

in inflammations as mediators go to the bone marrow inducing faster

production of WBCs (more hematopoiesis). Therefore, a complete blood count

(CBC) is often tested for in hospitals to tell if there is an inflammation or no

(also can show the presence of anemia). The normal number of WBCs in the

blood is 8-11 thousand cells. In an inflammation this number increases to 15-

20 thousand cells. However, sometimes we notice that the number can go up

to 40, 50 or even 70 thousand. If such a thing happens with any of your

patients you are supposed to get scared... This could mean that your patient is

having leukemia (cancer) or it could simply be that his body has over-reacted

to the mediators. To figure this out you take the sample to the lab and see on a

machine (flow cytometry test) whether the cells are polyclonal (not cancerous)

or monoclonal (cancerous). If they are polyclonal this means that his body

simply gave an exaggerated response and that this is a leukemoid reaction

(leukemia-like reaction).

Other systemic effects include tachycardia (heart rate becomes above normal),

chills and rigors (shivering due to the fever, rigors is a more intense type of

shivering than chills), decreased and cold sweating (especially just before a

shock), anorexia (فقدان الشهية), somnolence (sleepiness) and malaise (general

feeling of discomfort).

Sepsis and Septic Shock

Sepsis refers to the damage caused to the body cells and tissues as a result of

the response to infection. When the damage becomes very serious and the

blood pressure becomes very low and abnormalities in metabolism are seen

the sepsis has turned into a septic shock.

Usually caused by a gram-negative bacterial infection (can be gram-positive

but the gram-negative is more common and more dangerous. E.g. E. coli,

pneumonia, etc.).

It often happens in hospitals (i.e. hospital acquired) and patients often die.

Many mediators are involved in this condition and they can lead to DIC

(disseminated intravascular coagulation). Small clots appear in blood vessels all

over the body causing microinfarcts (can be thousands). To save a patient from

death here a very good level of treatment is needed and indeed patients do die

in many of these cases. A hypotensive shock can also occur [blood pressure

decreases as cardiac output decreases, (blood pressure = cardiac output *

peripheral resistance of blood vessels)], insulin resistance can develop and

hypoglycemia can occur (too many mediators lead to the development of

insulin resistance and the glucose is used up by the cells by glucose entering to

the cells with calcium ions, this results in both calcium ions and glucose

becoming low in blood so hypocalcemia and hypoglycemia develop). To

decrease the problem, you need to give a sugar and insulin to the patient.

Septic shocks can happen from non-infectious causes like severe trauma or

severe injurious effects (like pancreatitis and severe burns).

As sepsis develops due to mediators, the conditions described above fall under

the category of “systemic inflammatory response syndrome” (SIRS).

Extra paragraph

The granulomas of TB tend to contain necrosis ("caseating tubercules"), but non-necrotizing

granulomas may also be present. Multinucleated giant cells with nuclei arranged like a horseshoe

and foreign body giant cells [are often present, but are not specific for tuberculosis. A definitive

diagnosis of tuberculosis requires identification of the causative organism by microbiologic cultures.