Ain Shams University, Faculty of Pharmacy

Department of ……………….
DO NOT WRITE YOUR NAME OR ID
Degree: Bachelor of pharmacy
Year/Level: Second year(Level 3)
Course Title: Pathology
Course Code: 352/m
Academic Year: Second Semester 2019-2020

Topic Title:……………………………………..

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1-Metastatic calcification :
Metastatic calcification is deposition of calcium salts in normal tissues . This is due to high calcium
phosphate product in the blood and may result from hyperphosphatemia and hypercalcemia or both . It's
commonly related with sarcoidosis, metastatic disease, hyperparathyroidism and myeloma. For patients
with hypermetabolic conditions with extended bed rest periods the metastatic calcification is intensified.(1)
A-Excessive mobilization of calcium from the bones :
Causes :1.Hyperparathyrodism which may be primary such as due to parathyroid adenoma or secondry
such as from parathyroid hyperplasia , chronic renal failure etc.
2.Prolonged immobilization of a patient resulys in tissue atrophy of the bones and hypercalcemia.
3.Bony destructive lesions such as multiple myeloma and metastatic carcinoma.
4.Hypercalcemia as a part of paraneoplastic syndrome e.g in breast cancer.
B-Excessive absorption of calcium from the gut :
Causes :1.Hypervitaminosis D from high intake.
2.Milk-alkali syndrome caused by excessive oral intake of calcium in the form of milk and administration
of calcium carbonate in the treatment of peptic ulcer.
3.Idiopathic hypercalcemia of infancy ( Williams syndrome ).
4.Renal causes such as in renal tubular acidosis.(2)
Calcification sites : Metastatic calcification may occur in any normal tissue of the body but preferentially
affects the following organs and tissues :
1.Kidneys , mainly in the tubular lumina and at the basement membrane of tubular epithelium resulting in
nephrocalcinosis.
2.Lungs , mainly in the alveolar walls.
3.Stomach , on the acid-secreting fundal glands.
4.Blood vessels , especially on the internal elastic lamina.
5.Cornea is another site affecte by metastatic calcification.
6.Synovium of the joint causing pain and dysfunction.(2)

(3)Metastatic calcification in normal tissue

( Heart ) (4)Metastatic calcification
in the
lung

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Differences between dystrophic and metastatic calcification :

Feature Dystrophic cacification Metastatic calcification

Definition Deposition of calcium salts in dead Deposition of calcium salts in normal

tissues tissues

Serum Ca level Normal Hypercalcemia

Ca metabolism Normal Deranged
Reversibility Generally irreversible Reversible upon correction of metabolic
disorer

Necrosis (caseous , liquefactive , fat ) , Hyperparathyroism (due to adenoma,

infarcts , thrombi , haematomas , dead
Causes
parasites , sclerosis , old scars , tumors ,
calcinosis cutis ,cysts
Pathogenesis Increase binding of phosphates with
necrotic and degenerative tissue ,which
in turn binds to calcium forming calcium
phosphate precipitates
hyperplasia , CRF) , bony destructive
lesion(e.g metastatic carcinoma,myeloma)
prolonged immobilization , hypercalcemia
of infancy , hypervitaminosis D , milk-
alkali syndrome
Increased precipitates of calcium
phosphate due to hypercalcemia at certain
sites e.g in lungs , stomach , cornea and
blood vessels

(2)
2-Ischemia :
Ischemia is a decrease in blood flow that leads to a decrease in tissue supply of oxygen and nutrients.
Ischemia may be reversible, in which case if blood flow is restored, the affected tissue will recover, or it
may be irreversible, leading to tissue death. Ischemia can also be acute due to a sudden decrease in blood
flow, or chronic because of a slow decrease in blood flow. Ischemia can take place in any part of the body.
Heart attacks and strokes also can be caused by ischemia. Although less well known, ischemia can also
affect the intestines, leading to abdominal pain, bloody stool, and even rupture or gangrene of the
intestines. Peripheral ischemia can lead to finger or toe loss or amputation of the limb. According to

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ischemia, pain is a typical symptom, but not always occurring. Cognitive, sensory or motor disorders may
result from brain ischemia. Intestinal ischemia and heart attacks may cause nausea and vomiting.(5)

Types of ischemia :
There are not so many different forms of ischemia, as different names are available according to the body
part, for instance:
1.Cardiac ischemia which is due to decreased blood supply and oxygen to the heart muscle.
2.Cerebral ischemia resulted from decrease in blood flow to the brain.
3.Focal ischemia which occurs in specific region of the brain [in the form of transient ischemic attack
(TIA) or Stroke ].
4.Global ischemia which affects large area of the brain.
5. Critical limb ischemia is a decrease in blood supply to arms or legs.
6.Mesentric ischemia affects the intestines , ischemic colitis is a reduced blood flow to the colon.
7. Cutaneous ischemia means a restricted blood supply to the skin layers resulting in uneven patchy
discoloration of the skin.
8. Cyanosis is bluish or purplish skin discolouration due to circulatory complications and low level of
oxygen in the blood (hypoxia).
9. Gangrene is a death of the tissue resulting from lack of blood flow.(6)

Ischemia is also classified into only two types : Embolic & Thrombotic :
1. Embolic ischemia: Embolic ischemia occurs when the blood clot or plaque on another site breaks down
and passes through the blood into another location of the body, and then lodges in an artery .
2. Thrombotic ischemia: Occurs when blockage is present in an artery that supplies blood to an organ .(6)

Causes of ischemia :
1-Heart : inadequate cardiac output resulting from ventricular fibrillation and arrest due to many reasons ,
heart block may result in hypoxic injury to the brain.
2-Arteries : the most popular and important causes of ischemia are due to obstruction in arterial blood
flow : A-Luminal occlusion of artery (embolism or thrombosis ) . B-Problems in arterial walls such as
hypothermia ,ergotism , vasospasm (e.g Raynaud's disease) , arteriosclerosis , polyarteritis nodosa
thrombongilitis obliterans (Buerger's disease) and severed vessel wall.
C-External pressure applied on an artery resulting from tight plaster , bandages, ligature and tourniquet .

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3-Veins : blockage of venous drainage may result in engorgement and occlusion to arterial blood flow
leading to ischemia : A-Luminal occlusion of the vein (thrombosis of mesenteric vein or cavernous sinus
thrombosis ) . B-Vessel wall of vein problems such as varicose vein of the legs . C-External pressure on
vein such as intussesception , strangulated hernia and volvulus .
4-Microcirculation : obstruction of capillaries , arterioles an venules.The examples include the following :
A-Luminal occlusion of microvasculature : i)By red cells (e.g acquired hemolytic anemia , sickle cell
anemia , infection by malaria). ii)By white blood cells (e.g chronic myeloid leukaemia). iii)Fat embolism
B- Microvasculature wall problems such as vasculitis (e.g Arthus reaction), injured small blood vessels by
frost-bite. C-External pressure on microvasculature like in bed sores.(7)

Complications :
The consequences of ischaemia vary from no change to sudden death . 1-No effects, if the collateral
channels develop sufficiently so that the effect of ischaemia is avoied. 2-Functional disturbances ,these
occurs if collateral channels provide blood during normal activity but the supply is not able to resist effort.
Examples are intermittent claudication and angina pectoris. 3-Cellular changes, cells may be affected by
partial and gradual ischaemia such as cloudy swelling, fatty change, ischaemic atrophy, and fibrosis
replacement. Infarction (The most popular effect resulting from ischemia ) occurs when blood supply
restriction is complete inducing tissue necrosis. 4-Sudden death resulting from cerebral and myocardial
infarction.(8)

3-Haemorrhage
Haemorrhage is defined as the leakage of blood from a blood vessel. The bleeding may be externally, or
internally into the serous cavities (e.g. haemoperitoneum ,haemothorax, haemopericardium), or into a
hollow viscus. Haematoma is classified as blood extravasation into the tissue with consequent swelling.
Ecchymose defines the haemorrhage when the blood is largely extravased through the skin and mucous
membranes. Purpuras are small areas of haemorrhages in the mucous membrane (up to 1 cm), while
petechiae are minute haemorrhages of pinhead size. Microscopic escape of erythrocytes into loose tissues
after significant congestion can occur and is identified as diapedesis.(8)

Types of haemorrhage :
Haemorrhage is classified into two types , it may be acute when the blood loss is severe and sudden or
chronic when the blood is repeatedly lost over a long period of time .(7)

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Etiology :
There are many causes of haemorrhage , The examples include the following :
1- Trauma to the vessel wall , for example : penetrating wound in the heart , during labour.
2- Vascular diseases e.g. atherosclerosis.
3- Elevated pressure within the vessels e.g. systemic hypertension causing cerebral haemorrhage.
4- Inflammatory lesions of the vessel wall e.g. polyarteritis nodosa , chronic peptic ulcer.
5- Spontaneous haemorrhage e.g. bleeding diathesis , acute leukaemias and scurvy .
6- Neoplastic invasion as in carcinoma of the tongue , vascular invasion followed by haemorrhage .(8)

Complications :
The effects of haemorrhage depend on 3 main factors: A- The site of haemorrhage B- The amount of blood
loss C- The speed of blood loss .
1- Up to 20% loss of blood volume ( acute or chronic ) usually has little impact, due to compensatory
mechanisms.
2- Acute loss of 33% of blood volume may be fatal.
3- Gradual loss of up to 50% of blood volume over a period of 24 hours may be not fatal.
4- Chronic haemorrhage usually induces iron deficiency anaemia.
5- Acute blood loss may result in severe immediate effects such as hypovolaemic shock.(7)

4-Reactive lymphadenitis :
In response to a wide variety of effects like microbial infections, drugs, environmental contaminants, tissue
damage, immune complexes, and malignant neoplasms, lymph nodes undergo reactive changes.
Nevertheless,inflammatory and immune responses, aside from primary malignant neoplasms and metastatic
tumour deposits, are the most likely reasons of lymph node enlargement. Those caused by the primary
inflammatory reaction are called reactive lymphadenitis, while those caused by primary immune reactions
are known as lymphadenopathy. Reactive lymphadenitis is a non-specific response and is classified into
acute and chronic types, each of which has a few variant forms.(8)

Acute Nonspecific Lymphadenitis

All types of acute inflammations can induce acute non-specific lymphadenitis  in the nodes draining the
region of inflamed tissue.  Most common causes are microbial infections and their products of breakdown,
and foreign bodies in the wound or circulation etc. Lymph nodes most commonly involved are: cervical
(due to oral cavity infections), inguinal (due to lower extremity infection), axillary (due to arm
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infection) and mesenteric (due to acute appendicitis, acute enteritis, etc.). Acute lymphadenitis is typically
mild and temporary but can be more serious sometimes. Acutely inflamed nodes are swollen, soft, and may
be fluctuating if deeply involved. The skin underneath is red and dry. Most cases heal entirely without
leaving any scar after infection control. Acute lymphadenitis changes into chronic lymphadenitis if the
inflammation doesn't subside.(8)

Morphologic features: Grossly, the involved lymph nodes are enlarged 2-3 times their normal size and
may exhibit abscess formation if the involvement is extensive.
The sinusoids are microscopically congested, widely distended, and oedematous, and include many
neutrophils. The lymphoid follicles are prominent with presence of several mitoses and phagocytosis.
Necrosis may take place in more severe cases and neutrophil abscesses may develop.(8)

Chronic Nonspecific Lymphadenitis

Chronic non-specific lymphadenitis, commonly referred to as reactive lymphoid hyperplasia, is a popular
form of draining lymph node inflammatory reaction as a response to antigenic stimuli such as frequent
attacks of acute lymphadenitis and malignant tumor lymph. Three types are classified according to the
pattern in chronic non-specific lymphadenitis, each with its own set of reasons. These are:
 Paracortical lymphoid hyperplasia is attributed to T-cell-dependent area hyperplasia. Among the
major causes are drug-induced immunological reactions (such as dilantin), vaccination, viruses
(such as infectious mononucleosis), and autoimmune disorders.
 Follicular hyperplasia is the most common pattern encountered especially in children. In addition to
nonspecific stimulation, there are also common causes: rheumatoid arthritis, syphilis,
toxoplasmosis and AIDS.(8)

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 (8)

 Sinus hyperplasia is a very common form occurring in regional lymph nodes draining
inflammatory lesions, or as the host's immune reaction to a draining malignant tumor or to its
products. Histological diagnosis is characterized by the expansion of the sinuses through the
proliferation of large histiocytes containing phagocytised material. Some researchers have
considered the involvement of sinus histiocytosis in the draining lymph nodes of cancer tissue ,
such as in breast carcinoma,  is to confer better prognosis in these patients due to strong immune
response from the host.(8)

(8)
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List of references :
1. Homeostasis P, Calcification ST. Bone Disease Resulting from Disturbances in Mineral
Homeostasis. Orthop Pathol. 2010;189–210.
2. Lecture 3 , Dr :Mohamed Mabrouk.
3. No Title. Available from: https://peir.path.uab.edu/wiki/IPLab:Lab_2:Metastatic_Calcification
4. No Title. Available from: https://www.slideshare.net/DeepakKumarGupta2/pathologic-
calcification-53513539
5. No Title. Available from: https://www.healthgrades.com/right-care/vascular-conditions/ischemia
6. No Title. Available from:
https://www.emedicinehealth.com/ischemia/article_em.htm#what_are_the_types_of_ischemia
7. Lecture 5 , Dr: Ahmed Abbas.
8. Mohan H. Harsh Mohan - Textbook of Pathology, 6th Edition. 2010. 130–165 p.

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