5th lecture (Calcium accumulation)

Question 1

Hyaline definition?

Answer 1

NOT a unique of chemical, it is an amorphous materiel made of a mixture of plasma proteins coagulated in certain areas, overlaps hyalinic necrosis. Could be intracellular or extracellular, both are stained pinkish in H.E. staining.
Fibrinoid necrosis could look similar.

Question 2

Hyalinic arteriosclerosis.

Answer 2

affecting arteries mostly in the kidney but can affect other areas as well.
Endothelial experienced a physical of chemical stress (hypertension or diabetes [high glucose]) the endothelial cells become leaky, thus plasma proteins may leak out into the wall and the smooth muscle cells make start to secrete ECM. (narrow lumen and thick wall = potential ischemia injury)

Question 3

Hyaline membrane disease

Answer 3

occurs in the lungs, under 2 conditions:

1. Infant respiratory distress syndrome
2. adult respiratory distress syndrome.

Question 4

Infant respiratory distress syndrome description?

Answer 4

Immature lungs; surfactant is not produced enough thus alveoli cannot open. Cyanosis and acidosis will follow.

Question 5

adult respiratory distress syndrome description?

HYALINE membrane disease

Answer 5

toxic effect or infection that destroy the endothelial cells. The endothelial cells may also become leaky in the lungs and coagulates around the alveoli blocking the gas exchange.

Question 6

Name the types of haline diseases?

Answer 6

1. Hyaline arteriosclerosis
2. Hyaline membrane disease
3. Hyaline glomeruli
4. Mallory hyaline

Question 7

Hyalinic glomeruli description?

Answer 7

glomerulonephritis (inflammation of the kidney). The capillarys in the kidney will be leaky, plasma protein and immune complex start to precipitate in glomeruli causing. The duct will obliterated by the precipitation of hyalinic material (plasma protein) obstruct the capillaries and glomeruli (END stage kidney disease)

Question 8

Mallory hyaline description?

Answer 8

A result of hepatocytes in alcohol injury the cytoskeleton precipitates in the cytoplasm to make an amorphous material.

Question 9

Pigments definiton?

Answer 9

colored substances, which are intracelular or
extracellular.
can be endogeneous: hemosiderin, RBC breakdown and Iron accumulates in the skin.
can be extrageneous: Tattoos,

Question 10

Name some important pigments?

Answer 10

1. Carbon
2. lipofuscin
3. hemosiderin

Question 11

Carbon inhalation; what occurs in the body?

Answer 11

Carbons enters the alveoli which is phagocytosed by macrophages which then goes into the lymph nodes. The lymph nodes are blackish in the parabronchial area.
It has no effect in the lungs.

Question 12

coal workers pneumoconiosis description?

Answer 12

a diseases caused by coal worker who are exposed to not only carbon, but also; Si and iron. When Si combines with hydroxide causes SiOH which are consumed by macrophages and they kill the macrophages, as the macrophages dies it leaks enzymes into the tissue causing inflammation. Causing fibrosis, progressive loss of lung.
This increases the resistance in the lung causing cor pulmonale.
silicosis: lung disease caused by silica inhalation.

Question 13

lipofuscin description?

Answer 13

lipofuscin is a wear-and-tear protein that appears in all organs, caused by lipid peroxidation of intracellular organs (mt. golgi, ER). Perinuclear localization of brown-yellow granular substance, that is delivered by lipids (lipifuscin).

Question 14

Brown atrophy of the heart description?

Answer 14

occurs in older patients, and patients with advanced disease or infection or end-stage-disease. When the heart is involved in degenerative disease.
Apical-basal shortening of the heart, causing a curvery coronary arteries, with sharp edges, and there is downward pointing of the heart.

Question 15

hemosiderin description?

Answer 15

hemosiderin is a granular pigment intracellular that is gold-yellow. hemosiderin is mostly Iron surrounded by apoferritin (Iron-apoferritin). Accumulation causes hemosiderosis which can be local or systemic.
LOCAL: common root (blue-brown of a bruise caused by breakdown of RBC and Hb is liberated and Iron is taken up by macropages and combined with apoferritin. Also induratio brunea pneumonia (brown color of lung)
SYSTEMIC: hemolysis; (toxic event, blood mismatch)

Question 16

why are bruises turn blue then brown?

Answer 16

breakdown of RBC and Hb is liberated and Fe taken up by macrophages forming hemosiderin.

Question 17

what is hemosiderin mostly made up of?

Answer 17

hemosiderin is a granular pigment intracellular that is gold-yellow. hemosiderin is mostly Iron surrounded by apoferritin (Iron-apoferritin).

Question 18

describe induratio brunea pneumonia.

Answer 18

Brown coloration of the lung. (local hemosiderin)
If the heart has some sort of pumping failure (myocardial infraction) or a patient has Mitral valve stenosis. blood has difficulty going into the left ventricle causing back pressure into the lung. pulmonary stenosis can also cause similar problems. The high pressure in the alveoli causes penetration of RBC into the alveoi which are taken up by macrophages which are stored as hemosiderin, causing the BROWN color of the lung.
macrophage cells with granules of hemosiderin can be seen in the spit of the patient, they are refereed to as HEART FAILURE CELLS.

Question 19

what are HEART FAILURE CELLS?

Answer 19

Increase blood pressure in the lungs causes RBC to enter the alveoli to be taken up by macrophages which form hemosiderin causing the brown color of the lung.
Macrophages with hemosiderin can be found in the sputum of the patient and are called HEART FAILURE CELLS.
Can be caused by: mitral stenosis

Question 20

hemochromatosis description?

Answer 20

Extensive accumulation of Iron in the body.

Question 21

hemosiderosis description?

Answer 21

form of iron overload disorder resulting in the accumulation of hemosiderin. Iron homeostasis is highly controlled. Macrophages store the Iron.
hepcidin regulates Iron uptake from the intestine. High Iron = high hepcidin, low iron - low hepcidin allows Fe to enter the intestine.
Hepcidin is coded by the HFE. Mutation the patient looses hepcidin resulting in uncontrolled Fe uptake.

Question 22

In the event of hepcidin mutation causing excessive Iron uptake, what are the effect of excessive Iron in the blood?

Answer 22

The macrophage Iron storage is saturated. The extra free Iron not taken up by the macrophages will be toxic to other cell by forming free radical and ROS by causing inflammation and fibrosis.
cirrhosis at the liver, fibrosis of the pancreas, they also accumulate everywhere but the above to organs are most effected.

Question 23

Define cirrhosis?

Answer 23

late stage of scarring (fibrosis) of the liver caused by many forms of liver diseases and conditions, such as hepatitis and chronic alcoholism
(hepatic failure for patient)

Question 24

Pancreas fibrosis causes what?

Answer 24

Brown diabetes due to the Iron accumulation in the pancreas causing the brown color of pancreas. The fibrosis destroy the langerhans islands causing diabetes.

Question 25

who are the most effected by the hemochromatosis mutation?

Answer 25

Most effected by males, symptoms start show at age 35-40 at which age the macrophage system is saturated by Iron, Women tolerate it more do to menstrual cycle they loose blood and Iron.
Drugs can bind Iron in food to block the Iron uptake.
patients with this disease have a 200x risk for hepatocellular carcinoma (liver cancer) during their lifetime.

Question 26

Melanin description?

Answer 26

endogenous pigment made by tyrosinase enzyme using Thyrosine. they are located in the basal layer of epidermis. The melanocytes have melanin in the cytoplasm, the cell are surrounded by epithelial cell to which they could transfer the melanin.
This is called EPIDERMAL MELANIN UNIT. Using hydrogen peroxide causes a loss of color.

Question 27

ephelis definition? (melanin)

Answer 27

A form of freckle. A flat red or light-brown spot on the skin that typically appears during the sunny months and fades in the winter.
It is caused by increased transfer of melanin by melanocytes, its more prominent during sunshine.

Question 28

Melasma definition? (melanin)

Answer 28

brown to gray-brown patches, usually on the face, with a risk factor during pregnancy. Its a Matt like skin color of the skin. Junctional alteration of melanocytes. There is a reversible increase in the amount of melanin produced.
When pregnancy is terminated this condition does disappear.

Question 29

Vitiligo definition? (melanin)

Answer 29

partial or complete loss of melanin. 2 forms;

• albinism: problem with the thyronase enzyme (complete)
• Autoantibodies against melanocytes (partial).

Question 30

melanocytic nevus defintion? (melanin)

Answer 30

melanocytes can be located a different areas of skin:
-At epidermis (epidermal nervis)
-epidermal and dermal area (junctional nervis)
-deep dermis (dermal, intradermal nervis)
During puberty there is migration of melanocytes downward in the skin. So nervus can come up after puberty or during puberty.

Question 31

melanoma malignum definiton? (melanin)

Answer 31

Neoplasm of melanoma.

Question 32

Calcification definition?

Answer 32

Precipitation in calcium salts in tissues and organs. The calcium salts may also contain Iron potassium, magnesium.

Question 33

what are the 2 forms of calcification?

Answer 33

1. dystrophy (occurs with normal calcium levels)

2. metastatic (occurs with hypercalcemic levels)

Question 34

Dystrophy calcification description?

Answer 34

Occurs with normal calcium levels. Morphology of calcium is an amorphous precipitation of material which could be intracellular or extracellular, blueish.
occurs in necrotic and dying cells, cells with mostly terminated state. The dystropic calcification may start extracellular (via cell debris) or intracellular (via mitochondaria)

Question 35

dystropic calcification occurs how?

Answer 35

membrane bound vesicle are about 200nm diameter, theses vesicles come from dying cells. An enzyme called membrane bound phosphatase, will cut phosphate groups from the lipid membranes, the phosphate will bind the calcium to form calcium phosphate which make crystals which propagate and make calcium deposits in the cell.
can occur extracellularly via cell debris or intraceullularly via the mitochondria which also has a similar enzyme (phosphatase).
INITIATION: phosphate binds calcium
PROPAGATION: calcium crystal grows

Question 36

Diseases related to dystropic calcification.

Answer 36

• calcifying aortic stenosis
• Artificial valves
• atherosclerosis
• neoplasm
• inflammation

Question 37

Describe calcifying aortic stenosis? (in the context of dystropic calcification)

Answer 37

in older patients (70+), wear and tear diseases. The maximum flexture of the valves when opening is used up, thus degenerative necrotic procedure occurs, Head up Calcification fixes the valve in place and thus unable to move as much = Stenosis
thus increases resistance in outflow, and hypertrophy of left ventricle.

Question 38

Describe Artificial valves? (in the context of dystropic calcification)

Answer 38

Surgical procedure of implanting organic or inorganic valves is common. Implantation of any valve predisposes the patient to calcification. There are 2 reasons for this;

1. the suture around the valve causes cell necrosis where fibrosis could occur and block valve movement.
2. cell debris/necrotic cells may build up and calcify the valves.

Question 39

describe atherosclerosis? (in the context of dystropic calcification)

Answer 39

Lipid core is predisposed to calcification. Calcified plaque. Since the core is made up of cell debris.

Question 40

Describe neoplasm? (in the context of dystropic calcification)

Answer 40

Neoplastic disease is made of 2 things:
1. stroma (stromal vascular system)
2. parenchymal
parenchymal are the neoplastic cells.
For the neoplastic cells to stay alive they have a vascular system and stroma.
when neoplastic cells grow faster then the vascular systems can provide there will be a necrotic area where calcium is picked up and calcification may occur.

Question 41

Neoplasm in the context of breast cancer.

Answer 41

Breast cancer (mostly ductus origin) ductus epithelium starts to grow into the ductus, BUT the oxygen supply drops towards the lumen, Thus in the intra-ductule area necrosis and calcification can occur.
NOTE: breast cancer X-ray showing micro-calcification could be a tool for cancer diagnosis.

Question 42

Neoplasm histological characteristics, define psammoma bodies?

Answer 42

papillary cancer of thyroid or carcinoma of the ovary, may have laminated, ring like precipitation of calcium called psammoma bodies. In certain neoplasm characteristic dystorpic calcification can occur called psammoma bodies in the thyroid and ovary.

Question 43

Inflammation in the context of calcium deposition?

Answer 43

Example: tuberculosis which occurs moslty in the upper lobe of the lungs. It is composed of; central necrosis if inflammatory cells surrounding it. In the central area the caseous necrosis made by the calcium. It can be seen in the X-ray.

Question 44

Metastatic calcification description?

Answer 44

occurs in relation to hypercalcemia. Which could be do to;

1. hyperparathyroidism; secretion of PTH (parathyroid hormone) mobilizing of the Ca from bone and Ca uptake from GI. Could by hyperplasia of neoplasm of the gland.
2. Bone destruction. metastatic cancer in the bone that dissolved the bone (plasma cell myeloma)
3. Renal failure (causes secondary parathyroidisim)

Question 45

where can Calcium precipitation occur during metastatic calcification. (PTH increase)

Answer 45

it precipitation in areas where acid secretion occurs. because acidic secretion means alkaline in tissue which facilitates the precipitation of calcium.
1. Lungs (carbon monoxide is exhaled in the lungs, alkaline)
2. Kidney (phosphate is secreted here)
3. Stomach (where acid is secreted)
This precipitation does NOT disrupt the normal function of the organ.

Question 46

How can Renal failure cause secondary parathyroidism

Answer 46

since there is a balance between phosphate and calcium level. If Phosphate level increase Calcium level decrease and visa-versa. In the kidney the phosphate is secreted by the kidney, but during failure there is retention. The retention of phosphate causes hyperphosphatemia which reduces the Calcium level, and since Calcium concentration is a direct signal for PTH release. Low calcium level increase PTH secretion and cause parathyroidism.