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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.
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