Histopathology Laboratory - cell injury, cancer and Mitochondrial Disease Questions:

Histopathology Lab

Task 1. (P)

Cell injury:

The term cell injury is used to describe a state in which the capacity for physiological adaptation is exceeded. This may occur when the stimulus is excessive or when the cell is no longer capable to adapt without suffering some form of damage (injury).

Cell death:

There are different types of cell death, one type of cell death is known as necrosis which is caused by external factors. Necrosis is cell death within a living organism.

There is also apoptosis which is programmed cell death such as loss of webbing in between fingers in a human foetus.

Also there is general cell death where cells in a dead organism undergo autolysis, this is where they self destruct due to the organism being deceased.

Result of cancer from cell injury:

Cancer harms the body when damaged (injured) cells divide uncontrollably to form lumps or masses of tissue called tumors; tumors can grow and interfere with the digestive, nervous, and circulatory systems, and they can release hormones that alter body function.

Cancer is ultimately the result of cells that uncontrollably grow and do not die. Normal cells in the body follow an orderly path of growth, division, and death. Programmed cell death is called apoptosis as previously mentioned, and when this process breaks down, cancer begins to form. Unlike regular cells, cancer cells do not experience programmatic death and instead continue to grow and divide. This leads to a mass of abnormal (injured) cells that grow out of control causing cancers.

Cells can experience uncontrolled growth if there are damages or mutations to DNA, and therefore, damage to the genes involved in cell division. Four key types of gene are responsible for the cell division process: oncogenes tell cells when to divide, tumor suppressor genes tell cells when not to divide, suicide genes control apoptosis and tell the cell to kill itself if something goes wrong, and DNA-repair genes instruct a cell to repair damaged DNA.

Cancer occurs when a cell's gene mutations make the cell unable to correct DNA damage and unable to commit suicide. Similarly, cancer is a result of mutations that inhibit oncogene and tumor suppressor gene function, leading to uncontrollable cell growth.

Task 2. (M)

After a stroke or heart attack enzymes may be released from the damaged tissues into the blood; troponin, creatine, phosphokinase and transaminases are the main enzyes which are released. When these are present in the blood stream, this indicates necrosis (cell death) or damage to the plasma membranes. As a result of the damage, the intracellular proteins leak into the blood stream.

CPK test; Creatine kinase

Creatine phosphokinase (CPK) is an enzyme found mainly in the heart, brain, and skeletal muscle. CPK is composed of 3 isoenzymes (Multiple forms of ...

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Task 2. (M)

CPK test; Creatine kinase

Creatine phosphokinase (CPK) is an enzyme found mainly in the heart, brain, and skeletal muscle. CPK is composed of 3 isoenzymes (Multiple forms of enzymes) that differ slightly in structure:

•CPK-1 (also called CPK-BB) is concentrated in the brain and lungs
•CPK-2 (also called CPK-MB) is found mostly in the heart
•CPK-3 (also called CPK-MM) is found mostly in skeletal muscle

Because the CPK-1 isoenzyme is predominately found in the brain and lungs, injury to either of these organs (for example, stroke or lung injury due to a pulmonary embolism) are associated with elevated levels of this isoenzyme.

CPK-2 levels rise 3 - 6 hours after a heart attack. If there is no further damage to the heart muscle, the level peaks at 12 - 24 hours and returns to normal 12 - 48 hours after tissue death. CPK-2 levels do not usually rise with chest pain caused by angina, pulmonary embolism (blood clot in the lung), or congestive heart failure.

The CPK-3 isoenzyme is normally responsible for almost all CPK enzyme activity in healthy people. When this particular isoenzyme is elevated, it usually indicates injury or stress to skeletal muscle.

Lactic acid dehydrogenase (LDH) is most often measured to check for tissue damage. The enzyme LDH is in many body tissues, especially the heart, liver, kidney, skeletal muscle, brain, blood cells, and lungs.

But generally cardiac enzyme studies measure the levels of the enzyme creatine phosphokinase (CPK, CK) and the protein troponin in the blood. Low levels of these enzymes and proteins are normally found in the blood, but if your heart muscle is injured, such as from a heart attack, the enzymes and proteins leak out of damaged heart muscle cells, and their levels in the blood stream rise.

Task 3. (D)

Mitochondrial Disease Questions:

1.)

a. Georgina’s main symptoms are tiredness, weak muscles, problems with balance, coordination and nerve functions.

b. The nerve and muscle tissues are the most affected tissues.

2.) As Georgina’s GP stated one of her main symptoms is problems with nerve functions, the table shows data on the oxygen consumption of some organs and tissues.

The oxygen consumption per mass of tissue on the brain row is extraordinary high compared to other results in the table being 3.08 and the other data does not range above 2, since the brain oxygen consumption per mass of tissue intake is high this could explain why Georgina is having nerve problems due to her brain controlling the functions of nerves and the intake of oxygen being to high; also this explains why her mental development is slightly retarded.

Georgina’s GP also states another one of her main symptoms is problems with muscle functions, once again the table of data shows a result of 8.63 for muscles which is highly above other results featured in the table for oxygen consumption of organ / tissue; this high intake result may explain why Georgina is having problems with muscle function which is there for causing balance and coordination issues for her due to the correct control of muscles being required for good coordination.

3.) The main health risks associated with free radical damage is the DNA found in the mitochondria. Mitochondria are small membrane-enclosed regions of a cell which produce the chemicals a cell uses for energy. Mitochondria are the "energy factory" of the cell. Every cell contains an enormous set of molecules called DNA which provide chemical instructions for a cell to function.

This DNA is found in the nucleus of the cell, which serves as the control centre of the cell, as well as in the mitochondria. The cell automatically fixes much of the damage done to nuclear DNA however; the DNA in the mitochondria cannot be readily fixed.

This process causes extensive DNA damage to accumulate over time and shut down mitochondria, causing the cells to die and the organism to age.

This free radical generation process can disrupt all levels of cell function; this is why free radical damage is thought to be such a basic mechanism of tissue injury. It damages the body at the cellular level.

Free radicals can cause LDL (bad) cholesterol in the blood to stick to the walls of the blood vessels, resulting in atherosclerosis, a leading cause of heart disease. They can damage parts of the eye, resulting in cataracts or macular degeneration (a progressive condition leading to blindness). And if they affect cell reproduction, they can cause different forms of cancer.

4.)

a. The chemical curcumin which is found in the spice turmeric prevents mutations in mitochondrial DNA which therefore prevents abnormalities in cytochrome oxidase which therefore prevents the high build up of free radicals.

Due to the defects in cytochrome oxidase being associated with Alzheimer’s disease and normal aging process, this may be why the studies show the incidence of Alzheimer’s disease in the aging process of India is lower than in the west due to the majority of the Indian population consuming curry which mostly contains the spice turmeric.

b. Make sure Georgina eats food which contains high levels of the spice turmeric due to it containing the chemical curcumin, curcumin will theoretically help prevent mutations of Georgina’s mitochondrial DNA and which in Georgina’s case should help in the lacking of cytochrome oxidase and will therefore help increase the levels of ATP produced which will further more provide her with more energy which will help in reducing muscle weakness and tiredness.

Also if Georgina has high levels of radicals in her cells, it may help for her to have a diet high in antioxidants such as vitamin C, beta-carotene and vitamin E. These can be found in fresh fruit and vegetables.

5. (Also refer to sheet – Q.5.)

The electron transport chain comprises an enzymatic series of electron donors and acceptors. Each electron donor passes electrons to a more electronegative acceptor, which in turn donates these electrons to another acceptor, a process that continues down the series until electrons are passed to oxygen, the most electronegative and terminal electron acceptor in the chain. Passage of electrons between donor and acceptor releases energy, which is used to generate a proton gradient across the mitochondrial membrane by actively pumping protons into the intermembrane space, producing a thermodynamic state that has the potential to do work being in this case muscle contraction. The entire process is called oxidative phosphorylation, since ADP is phosphorylated to ATP using the energy of hydrogen oxidation in many steps.

A small percentage of electrons do not complete the whole series and instead directly leak to oxygen, resulting in the formation of the superoxide radicals, a highly reactive molecule that can cause cell and genetic damage which is what is taking place with Georgina.

6.)

Lactic acid is an acid produced by cells during chemical processes in the body that do not require oxygen (anaerobic metabolism). Anaerobic metabolism occurs only when too little oxygen is present for the more usual aerobic metabolism (oxygen requiring).

Pyruvate can be made from glucose through glycolysis; pyruvate supplies energy to living cells through the citric acid cycle (also known as the Krebs cycle) when oxygen is present (aerobic respiration), and alternatively ferments to produce lactate when oxygen is lacking (fermentation).

Basically, reduced coenzyme produced in glycolysis can’t be oxidized via the electron transport chain, so pyruvate which is the final product of glycolysis, will be reduced to lactate in anaerobic respiration.