What is Pathology and What Does a Pathologist Do?

A pathologist is a medical professional who examines bodies and body tissue. They are also responsible for conducting lab tests. A clinical pathologist is an essential part of medical teams who reach diagnoses for patients. After completing medical school, an individual must also complete three years of advanced medical education in a residency program before they are eligible to take board certification exams. Most pathologists are trained in both anatomical and clinical pathology.

The Role of Blood and Pathology Tests

Blood and pathology tests are essential for detecting, diagnosing, and treating disease. The term, “pathology” means the study of disease as well as causes and progression. There are a variety of pathology tests including blood tests, urine, stool (feces), and body tissue testing. Pathologists interpret the results of blood and pathology tests. They are looking for abnormalities in the samples that may indicate the presence of disease or health risks like cancer, chronic illnesses, or pre-diabetes. 

Why Blood and Pathology Tests Are Ordered

While pathology plays a role in detecting and diagnosing diseases, the tests are also important for other reasons including:

·   Properly treating a disease

·   Monitoring the progression of disease

·   Preventing disease

·   Determining the future risk of disease

·   Aiding research for new treatment options

·   Ensure the safety of treatment and procedures

When a doctor or specialist requests pathology tests it’s usually due to a concern about your health risks. A pathology test is effective for discovering if a problem or concern exists.

Types of Tissue Pathologists Examine

A pathologist is trained to examine tissue samples including samples as small as a dozen cells. Tissue cells may be obtained by aspiration or a needle biopsy. Larger tissue samples are surgically removed.

What do clinical pathologists do?

A clinical pathologist examines blood, urine, and other types of bodily fluids under a microscope. They are watching for the presence of certain chemicals or other substances. Their test results often determine a diagnosis or treatment option. Specimens used in clinical pathology include:

·   Blood Samples are used in many tests and can be checked in a variety of ways whole, plasma (the remaining fluid after red and white blood cells are removed), or serum (the clear fluid that separates from the blood during clotting).

·   Urine Samples are collected in a variety of ways including catheterization, clean catch specimen, or randomly.

·   Sputum Samples or phlegm samples are coughed into a clean container.

·   Stool Samples are often examined for the presence of blood.

·   Other Bodily Fluid Samples may include spinal fluid, pleural fluids, belly fluids, joint fluids, or bone marrow.

Clinical pathologists are often responsible for blood banks at hospitals. Their duties include collecting and processing blood products. They may also look at transfusion reactions or check tissue compatibility for transplants.

Conclusion

Pathology is a medical field that is quickly becoming more specialized. Pathologists provide experience and expertise when it comes to interpreting laboratory test results and evaluating cells, tissue, and organs in order to diagnose disease. A pathologist may determine a specific type of cancer and what stage it is in so that appropriate treatment can be recommended. In a quickly advancing technological age, their work is far from done and their importance continues to become apparent.

https://www.mskcc.org/cancer-care/diagnosis-treatment/diagnosing/role-pathology

https://pathology.uic.edu/understanding-your-pathology-report/

https://www.rcpath.org/discover-pathology/what-is-pathology.html

https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=85&contentid=P00955

https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/Blood-and-pathology-tests

https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/the-pathologist

Cancer Therapy

Thanks to extended research from human tissue samples we have been able to make major breakthroughs in cancer research. In the twenty-first century, evidence, both epidemiologically and clinically, have supported that the changes in whole-body metabolism can affect oncogenesis, the progression of tumors, and the response of tumor to therapy. It has been observed that metabolic conditions such as hyperglycemia, obesity, hyperlipidemia, and insulin resistance are associated higher with risk of cancer development, accelerated progression of tumors, and poor clinical outcome. Due to these findings, many clinical studies indicate that statins and metformin may help in decreasing cancer-related mortality and morbidity. Phenformin is another drug used to treat diabetics that can help with anticancer effects. However, phenformin was discontinued in the late 1970s due to a high incidence of lactic acidosis. Metformin is the most commonly used antihyperglycemic agent globally. It has an optimal pharmacokinetic profile with:

·         50 – 60% of absolute oral bioavailability

·         Slow absorption

·         Negligible binding to plasma protein

·         Broad tissue distribution

·         No hepatic metabolism

·         Limited drug interactions

·         Rapid urinary interaction

It also has an exceptional safety profile as there is a low number of individuals who have side effects. Statins also have a great safety profile and is currently used by a large population.

Cancer and Cellular Metabolism

The accumulation of evidence has suggested that malignant transformation is linked to changes that affect several factors of metabolism. Metabolic rearrangements associated with cancer have been linked with the inactivation of tumor suppressor genes and activation of proto-oncogenes. However, the accumulation of metabolites such as fumarate, succinate, and 2-hydroxyglutarate (2-HG) drives oncogenesis through the signal transduction cascades. Conclusively, these observations support the notion that signal transduction and intermediate metabolism are associated.

a)       Oncogenes and Metabolism

The signaling pathways from oncogenic drivers are linked to metabolic alterations due to cancer. For example, the expression of the PKM2 (an M2 isoform of pyruvate kinase) encourages the alteration of glycolytic intermediates in the direction of anabolic metabolism while regulating both transcriptional and post-transcriptional program that leads to the addiction of glutamine.

b)      Oncosuppressors and Metabolism

There are some oncosuppressor proteins that can regulate cellular metabolism. The inactivation of tumor suppressor p53 happens in more than 50% of all neoplasms causes a variety of metabolic consequences that could potentially stimulate the Warburg effect. P53 can possibly suppress the transcription of GLUT4 and GLUT1 and stimulate the expression of apoptosis regulator (TIGAR), TP53 induced glycolysis, SCO2, glutaminase 2 (GLS2) and many other pro-autophagic factors. It also interacts physically with glucose-6-phosphate-dehydrogenase (G6PD) with RB1-inducible coiled-coil 1 (RB1CC1).

c)       Oncometabolites and Oncoenzymes

It was found that metabolites can contribute to oncogenesis when mutations such as fumarate hydratase (FH) and succinate dehydrogenase (SDH) was linked to sporadic and familial types of cancer including pheochromocytoma, leiomyoma, renal cell carcinoma, and paraganglioma. once the enzymatic activity of SDH and FH is disrupted, succinate and fumarate accumulate resulting in oncogenesis.

Targeting Cancer Metabolism

The metabolic targets for cancer therapy rewiring of cancer cells is seen as a promising source for new drug targets. Some different approaches have resulted in the identification of agents that can help with targeting glucose metabolism for cancer therapy. However, the low number of metabolic inhibitors reflect the recent rediscovery of the field. There are also some concerns about the uniformity between malignant cells and non-transformed cells that are undergoing proliferation.

a)       Targeting Bioenergetic Metabolism

Some cancer-associated alterations such as the Krebs cycle, glycolysis, glutaminolysis, mitochondrial respiration, and fatty acid oxidation have been studied as potential sites for drug therapy.

b)      Targeting Anabolic Metabolism

The anabolic metabolism in cancer cells increases the output from nucleotide, protein, and protein biosynthesis pathways to help with the generation of new biomass in rapidly proliferating cells (includes both normal and malignant). A high metabolic flux through the pentose phosphate pathway is vital to cancer cells as it generates ribose-5-phosphate and nicotinamide adenine dinucleotide phosphate (NADPH).

c)       Targeting Other Metabolic Pathways

Other pathways involved in the adaptation to metabolic stress may provide drug targets for cancer therapy. This applies to autophagy, hypoxia-inducible factors 1, and nicotinamide adenine dinucleotide metabolism. A competitor of nicotinamide phosphoribosyltransferase (NAMPT) known as FK866 has been observed to have antineoplastic effects in murine tumor models.

Conclusion

The extensive metabolic rewiring in malignant cells provides a large number of possible drug targets. Many agents that target metabolic enzymes are used for decades while others are being developed. Therefore, the use of metabolic modulators that could be complicated by the similarities of highly proliferating normal cells and metabolism of malignant cells, there might be a chance to harness the antineoplastic activity of these drugs clinically. While many efforts were focused on merging metabolic modulators and targeted anticancer drugs, there may be a common view that metabolism and signal transduction are mostly independent if not separate entities. More research is needed to study the extent of how the metabolic functions of oncosuppressive and oncogenic systems contribute to the biological activity.

References:

Galluzzi L, Kepp O, Vander Heiden MG, Kroemer G. Metabolic targets for cancer therapy. Nature Reviews Drug Discovery. 2013; 12: 829-846.