Cellular injury and cell death can occur through necrosis or apoptosis. Necrosis is unregulated cell death due to external factors like hypoxia or toxins. It is characterized by cellular swelling, membrane rupture, and inflammatory responses. Apoptosis is regulated cell death that occurs normally or in response to DNA damage. The cell shrinks and fragments into membrane-bound vesicles that are phagocytosed without inflammation. Both can result from ATP depletion, calcium flux, reactive oxygen species, or endoplasmic reticulum stress. The pattern of necrosis in tissue provides clues to the underlying cause, such as coagulative necrosis from ischemia.
Necrosis and apoptosis are both forms of cell death, but they differ significantly. Necrosis is premature cell death caused by external factors like infection, toxins, or physical trauma. It results in the uncontrolled release of cellular contents and causes inflammation. Apoptosis is programmed cell death that occurs as part of natural biological processes. It is an actively regulated and controlled process where cells play an active role in their own death, avoiding inflammation.
Sansar Babu Tiwari presented a slide presentation on hematology focusing on eosinophilia. The presentation included:
1. Analysis of a peripheral blood smear showing 53% eosinophils, with normal RBC and platelet morphology.
2. A discussion of eosinophil morphology, differentiation, and granule composition. Eosinophils arise from bone marrow and traffic to tissues, where they play roles in immunity and tissue damage.
3. An overview of the causes of eosinophilia, which can be secondary/reactive to conditions like parasites, allergies, and drugs, or primary/clonal due to disorders like cancers, idiopathic hypereosin
The document discusses the outcomes of acute inflammation and their morphological patterns. There are three potential outcomes of acute inflammation: 1) complete resolution, 2) healing by fibrosis, or 3) chronic inflammation. It also describes four main morphological patterns of acute inflammation: serous, fibrinous, suppurative (abscess formation), and ulcerative. Each pattern is associated with different clinical presentations and histological features.
Robbins Chapter 1.. Cell as a unit of health and diseaseAshish Jawarkar
The document provides an overview of key cellular structures and functions, including the genome, plasma membrane, organelles, cellular communication, the extracellular matrix, cell division, and stem cells. It discusses how cells maintain essential housekeeping functions and how differentiation occurs at the epigenetic level despite all cells containing the same genetic material. Stem cells are described as being able to both self-renew and differentiate into specialized cell types to replace damaged or aging cells.
This document discusses several staining methods used for staining nerve tissue, including H&E staining, Nissl staining, Luxol-fast blue staining, Kluver–Barrera staining, Bodian silver staining, Holzer staining, and Gallyas–Braak staining. Each method selectively stains different components of nerve tissue such as cell nuclei, myelin sheaths, nerve fibers, and abnormal protein deposits. The staining methods allow clear visualization of neuronal structures and identification of lesions or abnormalities in nervous system tissue.
Giant cell lesions of bone include both reactive and neoplastic conditions characterized by the presence of multinucleated giant cells. Reactive giant cell lesions include giant cell reparative granuloma and brown tumor of hyperparathyroidism. Benign neoplastic giant cell lesions include giant cell tumor and aneurysmal bone cyst. Giant cell tumor is the most common, occurring most frequently in long bones of the extremities in young and middle aged adults. Histologically it is characterized by uniformly distributed osteoclast-like giant cells and mononuclear stromal cells that express RANKL.
This document outlines the various causes and mechanisms of cell injury. It discusses how oxygen deprivation, physical and chemical agents, infections, immune reactions, and nutritional imbalances can all lead to cell injury through mechanisms like ATP depletion, mitochondrial damage, calcium dysregulation, and oxidative stress. These mechanisms disrupt critical cellular processes and structures like membranes, ultimately leading cells to die through necrosis or apoptosis.
Necrosis and apoptosis are both forms of cell death, but they differ significantly. Necrosis is premature cell death caused by external factors like infection, toxins, or physical trauma. It results in the uncontrolled release of cellular contents and causes inflammation. Apoptosis is programmed cell death that occurs as part of natural biological processes. It is an actively regulated and controlled process where cells play an active role in their own death, avoiding inflammation.
Sansar Babu Tiwari presented a slide presentation on hematology focusing on eosinophilia. The presentation included:
1. Analysis of a peripheral blood smear showing 53% eosinophils, with normal RBC and platelet morphology.
2. A discussion of eosinophil morphology, differentiation, and granule composition. Eosinophils arise from bone marrow and traffic to tissues, where they play roles in immunity and tissue damage.
3. An overview of the causes of eosinophilia, which can be secondary/reactive to conditions like parasites, allergies, and drugs, or primary/clonal due to disorders like cancers, idiopathic hypereosin
The document discusses the outcomes of acute inflammation and their morphological patterns. There are three potential outcomes of acute inflammation: 1) complete resolution, 2) healing by fibrosis, or 3) chronic inflammation. It also describes four main morphological patterns of acute inflammation: serous, fibrinous, suppurative (abscess formation), and ulcerative. Each pattern is associated with different clinical presentations and histological features.
Robbins Chapter 1.. Cell as a unit of health and diseaseAshish Jawarkar
The document provides an overview of key cellular structures and functions, including the genome, plasma membrane, organelles, cellular communication, the extracellular matrix, cell division, and stem cells. It discusses how cells maintain essential housekeeping functions and how differentiation occurs at the epigenetic level despite all cells containing the same genetic material. Stem cells are described as being able to both self-renew and differentiate into specialized cell types to replace damaged or aging cells.
This document discusses several staining methods used for staining nerve tissue, including H&E staining, Nissl staining, Luxol-fast blue staining, Kluver–Barrera staining, Bodian silver staining, Holzer staining, and Gallyas–Braak staining. Each method selectively stains different components of nerve tissue such as cell nuclei, myelin sheaths, nerve fibers, and abnormal protein deposits. The staining methods allow clear visualization of neuronal structures and identification of lesions or abnormalities in nervous system tissue.
Giant cell lesions of bone include both reactive and neoplastic conditions characterized by the presence of multinucleated giant cells. Reactive giant cell lesions include giant cell reparative granuloma and brown tumor of hyperparathyroidism. Benign neoplastic giant cell lesions include giant cell tumor and aneurysmal bone cyst. Giant cell tumor is the most common, occurring most frequently in long bones of the extremities in young and middle aged adults. Histologically it is characterized by uniformly distributed osteoclast-like giant cells and mononuclear stromal cells that express RANKL.
This document outlines the various causes and mechanisms of cell injury. It discusses how oxygen deprivation, physical and chemical agents, infections, immune reactions, and nutritional imbalances can all lead to cell injury through mechanisms like ATP depletion, mitochondrial damage, calcium dysregulation, and oxidative stress. These mechanisms disrupt critical cellular processes and structures like membranes, ultimately leading cells to die through necrosis or apoptosis.
This document provides information about preparing and examining peripheral blood smears. It discusses how to make a good blood smear by ensuring the smear is evenly spread and covers most of the slide. The document also describes staining blood smears using the Leishman's stain method and examining smears under a microscope. Key things to observe during examination include the different types of white blood cells, red blood cell morphology, and any abnormal findings. Performing a manual differential count involves identifying 100 white blood cells and categorizing them by type.
Plasma cell neoplasms are clonal proliferations of plasma cells that produce monoclonal proteins. The key types are plasma cell myeloma, monoclonal gammopathy of undetermined significance, and plasmacytoma. Plasma cell myeloma is characterized by clonal plasma cell proliferation in the bone marrow causing osteolytic lesions and organ dysfunction. Diagnosis involves identifying monoclonal proteins by serum and urine protein electrophoresis and bone marrow biopsy showing clonal plasma cell infiltration. Genetic testing can further classify myeloma into hyperdiploid and non-hyperdiploid subtypes associated with different prognoses.
Chronic inflammation is defined as prolonged inflammation that lasts weeks or months, characterized by ongoing tissue destruction and healing simultaneously. It involves infiltration by mononuclear cells like macrophages, lymphocytes, and plasma cells, as well as tissue destruction and repair through angiogenesis and fibrosis. Chronic inflammation can be caused by bacterial, fungal, parasitic, or miscellaneous agents and is characterized by formation of granulomas consisting of activated macrophages, lymphocytes, and occasional plasma cells. Tuberculosis causes chronic inflammation through formation of tuberculous lesions containing caseous necrosis surrounded by lymphocytes, epithelioid cells, and giant cells.
This document summarizes information on pathological calcification and amyloidosis. It discusses two types of pathological calcification - dystrophic calcification, which occurs in dead or degenerating tissue despite normal calcium metabolism, and metastatic calcification, which results from hypercalcemia and occurs in normal tissues. It also covers the definition, chemical structure, classification, staining characteristics and morphological features of amyloidosis. In particular, it describes how amyloidosis can involve the kidney, spleen, liver and heart, and discusses the prognosis of generalized amyloidosis.
The document discusses myeloproliferative disorders (MPDs), which are clonal stem cell disorders characterized by increased blood cell counts and enlarged spleen and bone marrow. It focuses on chronic myeloid leukemia (CML), describing it as a MPD caused by a genetic mutation that results in uncontrolled white blood cell growth. CML progresses through chronic, accelerated, and blast phases, with symptoms ranging from fatigue to organ enlargement. Diagnosis involves blood and bone marrow tests detecting elevated white and platelet counts and the Philadelphia chromosome genetic abnormality associated with CML.
Salivary glands produce saliva and are composed of major and minor glands. The major glands are the parotid, submandibular, and sublingual glands. Salivary gland cytology can detect both benign and malignant lesions. Common benign findings include pleomorphic adenoma, Warthin's tumor, and basal cell adenoma cells. Malignant lesions include adenoid cystic carcinoma, mucoepidermoid carcinoma, and adenocarcinoma. Fine needle aspiration cytology allows diagnosis of salivary gland lesions with high sensitivity and specificity to guide treatment.
The document discusses acute myeloid leukemia (AML), including its pathophysiology, signs and symptoms, laboratory diagnosis, classification, and genetic abnormalities. AML results from the uncontrolled growth of immature myeloid cells in the bone marrow, preventing normal blood cell production and leading to symptoms like infections, anemia, and bleeding. Diagnosis involves blood and bone marrow tests to identify the percentage and type of immature blast cells present and any genetic mutations driving the cancer.
This document discusses myeloproliferative disorders (MPDs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis. MPDs are clonal stem cell disorders characterized by excessive proliferation of one or more myeloid cell lineages. Common features include increased proliferation, extramedullary hematopoiesis, marrow fibrosis, and peripheral blood cytopenias. The document defines each type of MPD and discusses their pathogenesis, morphology, clinical features, complications, investigations, and treatments.
1. The document discusses various hemodynamic disorders including edema, hyperemia, congestion, hemorrhage, thrombosis, embolism, infarction, and shock.
2. Edema results from fluid movement into tissues and can affect subcutaneous tissues, lungs, and brain. Congestion is the passive filling of tissues with blood due to impaired outflow.
3. Thrombosis is the formation of clots within vessels, which can then embolize and travel to other sites (embolism), potentially causing ischemic tissue damage or infarction if blood flow is not restored.
4. Shock represents a failure of circulation to maintain adequate tissue perfusion and oxygenation.
AML:ACUTE MYELOID LEUKAEMIA
for medical colleges teaching faculty and students as well. it includes AML causes , histopathological slides of subclasses of Acute myeloid leukemia, classification , diagnosis, management modalities, complications .Acute leukemias are stem cell disorders characterized by malignant neoplastic proliferation and accumulation of immature and non functional hematopoietic cells in the bone marrow.
The neoplastic cells show increased proliferation and/or decreased apoptosis.
If the defect primarily affects the common myeloid progenitor (CMP) then it is called Acute myeloid leukemia.
Acute myeloid leukemia (AML) is a neoplastic disease characterized by infiltration of the blood, bone marrow, and other tissues by proliferative, clonal undifferentiated cells of the hematopoietic system.
AML is the result of a sequence of somatic mutations in a multipotential primitive hematopoietic cell or, in some cases, a more differentiated progenitor cell.
It can be slow growing or rapidly fatal.
AML is the predominant form of leukemia during the neonatal period
Incidence : 1.5/100,000/year in infants decreases to approximately 0.4 per 100,000 children ages 5 to 9 years, increases gradually to 1.0 persons per 100,000 until age 25 years, and thereafter increases exponentially until the rate reaches approximately 25/100,000 persons.
AML accounts for 15 to 20 percent of the acute leukemias in children and 80 percent of the acute leukemias in adults.
Men > Women (4.5 : 3)
HEREDITY
1) Chromosomal aneuploidy like Trisomy 21 noted in Down syndrome
2) Defective DNA repair, e.g., Fanconi anemia, Bloom syndrome, and Ataxia telangiectasia
3) Congenital neutropenia ie Kostmann syndrome
4) Germline mutations of CCAAT/enhancer-binding protein α (CEBPA), runt-related transcription factor 1 (RUNX1), and tumor protein p53 (TP53) have also been associated with a higher predisposition to AML
RADIATION
Peaks after 5 to 7 yrs of exposure.
Therapeutic radiation alone seems to add little risk of AML but can increase the risk in people also exposed to alkylating agents.
CHEMICAL AND OTHER EXPOSURES
Exposure to benzene, plastic, rubber, petroleum products, paint, ethylene oxide, herbicides and pesticides can increase the risk.
Smoking can also increase the risk
DRUGS
Anticancer drugs are the leading cause of therapy-associated AML.
Alkylating agent–associated leukemias occur on average 4–6 years after exposure, and affected individuals have aberrations in chromosomes 5 and 7.
Topoisomerase II inhibitor–associated leukemias occur 1–3 years after exposure, and affected individuals often have aberrations involving chromosome 11q23.
Other agents like Chloramphenicol, phenylbutazone, and, less commonly, chloroquine and methoxypsoralen.
SYMPTOMS :
Present with nonspecific symptoms initially.
Fatigue is the first symptom
Fever with or without infection will be present in approximately 10% patients
Bleeding, easy bruising
occasional
This document provides an overview of practical pathology, including histopathology and cytopathology techniques. It discusses different types of biopsies like incisional, excisional, punch and needle biopsies. It also describes the general principles of gross examination and the histopathological techniques of fixation, dehydration, embedding, sectioning and staining tissue samples, most commonly hematoxylin and eosin or special stains. The document concludes with an overview of cytology techniques like exfoliative, abrasive and fine needle aspiration cytology as well as their indications and limitations.
- Benign inclusions are non-neoplastic ectopic tissue found in lymph nodes that can originate from various sources such as paramesonephric ducts, salivary glands, breast tissue, thyroid follicles, and squamous or mesothelial cells.
- Common types include epithelial inclusions resembling ducts or cysts, nevomelanocytic aggregates in capsules, and decidual tissues. Precise classification and identification is important to differentiate from metastatic adenocarcinoma.
- Inclusions are believed to develop through various mechanisms like implantation from tubal ostia, metaplasia of peritoneal tissues, or embryonic duct remnants. Their presence in lymph nodes is usually incidental
The document provides an overview of the nervous system and various neurological disorders. It describes the central nervous system including the brain and spinal cord, as well as the peripheral nervous system. Several neurological disorders are then discussed in detail, including seizures, dementia, Alzheimer's disease, strokes, headaches, meningitis, Parkinson's disease, multiple sclerosis, and brain tumors. For each disorder, the document outlines symptoms, causes, diagnosis, and treatment options.
The document discusses hematopoiesis, the process of blood cell production. It describes how hematopoietic stem cells in the bone marrow differentiate into the various blood cell lineages through the action of growth factors. This includes erythropoiesis, granulopoiesis, megakaryopoiesis, and lymphopoiesis. It also covers reactive conditions that can cause changes in white blood cell counts, such as infections and inflammatory states.
This document provides information about performing a peripheral blood smear examination, including the different types of blood smears, proper procedures for making blood smears, characteristics of a good smear, common causes of a poor smear, staining techniques, performing a manual differential count and assessing red blood cell morphology. Key steps include making wedge or spun smears from EDTA blood, allowing the smear to air dry before staining with Leishman's stain, examining under 10x, 40x and 100x magnification to perform white blood cell counts and differentials, and platelet and red blood cell morphology assessments. Causes of abnormal smears and signs of abnormal white blood cell morphology are also outlined.
Exfoliative cytology involves the microscopic study of cells that have been shed from epithelial surfaces, either spontaneously or through mechanical scraping, to detect malignant or precancerous lesions. A Pap test is a specific type of exfoliative cytology that involves collecting cells from a woman's cervix using a spatula or brush and examining them under a microscope to screen for cervical cancer and its precursors. The procedure involves collecting and fixing cells on a slide, staining the slide, examining it under a microscope, and communicating results.
The document provides an overview of neoplasia (new abnormal growth) and cancer. It discusses the history of cancer discovery from ancient Egypt and Greece to modern molecular understanding. Some key points covered include:
- The "hallmarks of cancer" which enable malignant growth including self-sufficiency in growth signals, evading growth suppression, altered metabolism, evading cell death, unlimited replication potential, sustained angiogenesis, tissue invasion and metastasis, and immune evasion.
- Molecular drivers of cancer like oncogenes which promote growth and tumor suppressor genes like RB and p53 which are inactivated, allowing uncontrolled cell division.
- Epidemiology factors in cancer incidence and risk including both modifiable (diet,
Cellular injury and cell death can occur through several mechanisms:
1. Reversible injury may occur when cells are stressed but can still adapt through changes like swelling. Irreversible injury leads to cell death.
2. Necrosis is caused by severe damage where cell contents leak out. Apoptosis is a programmed form of cell death where the cell dismantles itself. Autophagy is a process where cells digest their own components.
3. The causes of cellular injury include hypoxia, physical and chemical agents, infectious agents, immunological reactions, and genetic or nutritional factors. Cell death is identifiable through morphology changes in microscopy.
Reversible cell injury results in cellular swelling and fatty change due to failure of ion pumps and appearance of lipid vacuoles. If injury persists, irreversible changes occur like membrane damage, mitochondrial damage, calcium influx, and reactive oxygen species accumulation leading to cell death by necrosis or apoptosis. Necrosis involves loss of membrane integrity while apoptosis is a regulated pathway of cell fragmentation and phagocytosis.
This document provides information about preparing and examining peripheral blood smears. It discusses how to make a good blood smear by ensuring the smear is evenly spread and covers most of the slide. The document also describes staining blood smears using the Leishman's stain method and examining smears under a microscope. Key things to observe during examination include the different types of white blood cells, red blood cell morphology, and any abnormal findings. Performing a manual differential count involves identifying 100 white blood cells and categorizing them by type.
Plasma cell neoplasms are clonal proliferations of plasma cells that produce monoclonal proteins. The key types are plasma cell myeloma, monoclonal gammopathy of undetermined significance, and plasmacytoma. Plasma cell myeloma is characterized by clonal plasma cell proliferation in the bone marrow causing osteolytic lesions and organ dysfunction. Diagnosis involves identifying monoclonal proteins by serum and urine protein electrophoresis and bone marrow biopsy showing clonal plasma cell infiltration. Genetic testing can further classify myeloma into hyperdiploid and non-hyperdiploid subtypes associated with different prognoses.
Chronic inflammation is defined as prolonged inflammation that lasts weeks or months, characterized by ongoing tissue destruction and healing simultaneously. It involves infiltration by mononuclear cells like macrophages, lymphocytes, and plasma cells, as well as tissue destruction and repair through angiogenesis and fibrosis. Chronic inflammation can be caused by bacterial, fungal, parasitic, or miscellaneous agents and is characterized by formation of granulomas consisting of activated macrophages, lymphocytes, and occasional plasma cells. Tuberculosis causes chronic inflammation through formation of tuberculous lesions containing caseous necrosis surrounded by lymphocytes, epithelioid cells, and giant cells.
This document summarizes information on pathological calcification and amyloidosis. It discusses two types of pathological calcification - dystrophic calcification, which occurs in dead or degenerating tissue despite normal calcium metabolism, and metastatic calcification, which results from hypercalcemia and occurs in normal tissues. It also covers the definition, chemical structure, classification, staining characteristics and morphological features of amyloidosis. In particular, it describes how amyloidosis can involve the kidney, spleen, liver and heart, and discusses the prognosis of generalized amyloidosis.
The document discusses myeloproliferative disorders (MPDs), which are clonal stem cell disorders characterized by increased blood cell counts and enlarged spleen and bone marrow. It focuses on chronic myeloid leukemia (CML), describing it as a MPD caused by a genetic mutation that results in uncontrolled white blood cell growth. CML progresses through chronic, accelerated, and blast phases, with symptoms ranging from fatigue to organ enlargement. Diagnosis involves blood and bone marrow tests detecting elevated white and platelet counts and the Philadelphia chromosome genetic abnormality associated with CML.
Salivary glands produce saliva and are composed of major and minor glands. The major glands are the parotid, submandibular, and sublingual glands. Salivary gland cytology can detect both benign and malignant lesions. Common benign findings include pleomorphic adenoma, Warthin's tumor, and basal cell adenoma cells. Malignant lesions include adenoid cystic carcinoma, mucoepidermoid carcinoma, and adenocarcinoma. Fine needle aspiration cytology allows diagnosis of salivary gland lesions with high sensitivity and specificity to guide treatment.
The document discusses acute myeloid leukemia (AML), including its pathophysiology, signs and symptoms, laboratory diagnosis, classification, and genetic abnormalities. AML results from the uncontrolled growth of immature myeloid cells in the bone marrow, preventing normal blood cell production and leading to symptoms like infections, anemia, and bleeding. Diagnosis involves blood and bone marrow tests to identify the percentage and type of immature blast cells present and any genetic mutations driving the cancer.
This document discusses myeloproliferative disorders (MPDs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis. MPDs are clonal stem cell disorders characterized by excessive proliferation of one or more myeloid cell lineages. Common features include increased proliferation, extramedullary hematopoiesis, marrow fibrosis, and peripheral blood cytopenias. The document defines each type of MPD and discusses their pathogenesis, morphology, clinical features, complications, investigations, and treatments.
1. The document discusses various hemodynamic disorders including edema, hyperemia, congestion, hemorrhage, thrombosis, embolism, infarction, and shock.
2. Edema results from fluid movement into tissues and can affect subcutaneous tissues, lungs, and brain. Congestion is the passive filling of tissues with blood due to impaired outflow.
3. Thrombosis is the formation of clots within vessels, which can then embolize and travel to other sites (embolism), potentially causing ischemic tissue damage or infarction if blood flow is not restored.
4. Shock represents a failure of circulation to maintain adequate tissue perfusion and oxygenation.
AML:ACUTE MYELOID LEUKAEMIA
for medical colleges teaching faculty and students as well. it includes AML causes , histopathological slides of subclasses of Acute myeloid leukemia, classification , diagnosis, management modalities, complications .Acute leukemias are stem cell disorders characterized by malignant neoplastic proliferation and accumulation of immature and non functional hematopoietic cells in the bone marrow.
The neoplastic cells show increased proliferation and/or decreased apoptosis.
If the defect primarily affects the common myeloid progenitor (CMP) then it is called Acute myeloid leukemia.
Acute myeloid leukemia (AML) is a neoplastic disease characterized by infiltration of the blood, bone marrow, and other tissues by proliferative, clonal undifferentiated cells of the hematopoietic system.
AML is the result of a sequence of somatic mutations in a multipotential primitive hematopoietic cell or, in some cases, a more differentiated progenitor cell.
It can be slow growing or rapidly fatal.
AML is the predominant form of leukemia during the neonatal period
Incidence : 1.5/100,000/year in infants decreases to approximately 0.4 per 100,000 children ages 5 to 9 years, increases gradually to 1.0 persons per 100,000 until age 25 years, and thereafter increases exponentially until the rate reaches approximately 25/100,000 persons.
AML accounts for 15 to 20 percent of the acute leukemias in children and 80 percent of the acute leukemias in adults.
Men > Women (4.5 : 3)
HEREDITY
1) Chromosomal aneuploidy like Trisomy 21 noted in Down syndrome
2) Defective DNA repair, e.g., Fanconi anemia, Bloom syndrome, and Ataxia telangiectasia
3) Congenital neutropenia ie Kostmann syndrome
4) Germline mutations of CCAAT/enhancer-binding protein α (CEBPA), runt-related transcription factor 1 (RUNX1), and tumor protein p53 (TP53) have also been associated with a higher predisposition to AML
RADIATION
Peaks after 5 to 7 yrs of exposure.
Therapeutic radiation alone seems to add little risk of AML but can increase the risk in people also exposed to alkylating agents.
CHEMICAL AND OTHER EXPOSURES
Exposure to benzene, plastic, rubber, petroleum products, paint, ethylene oxide, herbicides and pesticides can increase the risk.
Smoking can also increase the risk
DRUGS
Anticancer drugs are the leading cause of therapy-associated AML.
Alkylating agent–associated leukemias occur on average 4–6 years after exposure, and affected individuals have aberrations in chromosomes 5 and 7.
Topoisomerase II inhibitor–associated leukemias occur 1–3 years after exposure, and affected individuals often have aberrations involving chromosome 11q23.
Other agents like Chloramphenicol, phenylbutazone, and, less commonly, chloroquine and methoxypsoralen.
SYMPTOMS :
Present with nonspecific symptoms initially.
Fatigue is the first symptom
Fever with or without infection will be present in approximately 10% patients
Bleeding, easy bruising
occasional
This document provides an overview of practical pathology, including histopathology and cytopathology techniques. It discusses different types of biopsies like incisional, excisional, punch and needle biopsies. It also describes the general principles of gross examination and the histopathological techniques of fixation, dehydration, embedding, sectioning and staining tissue samples, most commonly hematoxylin and eosin or special stains. The document concludes with an overview of cytology techniques like exfoliative, abrasive and fine needle aspiration cytology as well as their indications and limitations.
- Benign inclusions are non-neoplastic ectopic tissue found in lymph nodes that can originate from various sources such as paramesonephric ducts, salivary glands, breast tissue, thyroid follicles, and squamous or mesothelial cells.
- Common types include epithelial inclusions resembling ducts or cysts, nevomelanocytic aggregates in capsules, and decidual tissues. Precise classification and identification is important to differentiate from metastatic adenocarcinoma.
- Inclusions are believed to develop through various mechanisms like implantation from tubal ostia, metaplasia of peritoneal tissues, or embryonic duct remnants. Their presence in lymph nodes is usually incidental
The document provides an overview of the nervous system and various neurological disorders. It describes the central nervous system including the brain and spinal cord, as well as the peripheral nervous system. Several neurological disorders are then discussed in detail, including seizures, dementia, Alzheimer's disease, strokes, headaches, meningitis, Parkinson's disease, multiple sclerosis, and brain tumors. For each disorder, the document outlines symptoms, causes, diagnosis, and treatment options.
The document discusses hematopoiesis, the process of blood cell production. It describes how hematopoietic stem cells in the bone marrow differentiate into the various blood cell lineages through the action of growth factors. This includes erythropoiesis, granulopoiesis, megakaryopoiesis, and lymphopoiesis. It also covers reactive conditions that can cause changes in white blood cell counts, such as infections and inflammatory states.
This document provides information about performing a peripheral blood smear examination, including the different types of blood smears, proper procedures for making blood smears, characteristics of a good smear, common causes of a poor smear, staining techniques, performing a manual differential count and assessing red blood cell morphology. Key steps include making wedge or spun smears from EDTA blood, allowing the smear to air dry before staining with Leishman's stain, examining under 10x, 40x and 100x magnification to perform white blood cell counts and differentials, and platelet and red blood cell morphology assessments. Causes of abnormal smears and signs of abnormal white blood cell morphology are also outlined.
Exfoliative cytology involves the microscopic study of cells that have been shed from epithelial surfaces, either spontaneously or through mechanical scraping, to detect malignant or precancerous lesions. A Pap test is a specific type of exfoliative cytology that involves collecting cells from a woman's cervix using a spatula or brush and examining them under a microscope to screen for cervical cancer and its precursors. The procedure involves collecting and fixing cells on a slide, staining the slide, examining it under a microscope, and communicating results.
The document provides an overview of neoplasia (new abnormal growth) and cancer. It discusses the history of cancer discovery from ancient Egypt and Greece to modern molecular understanding. Some key points covered include:
- The "hallmarks of cancer" which enable malignant growth including self-sufficiency in growth signals, evading growth suppression, altered metabolism, evading cell death, unlimited replication potential, sustained angiogenesis, tissue invasion and metastasis, and immune evasion.
- Molecular drivers of cancer like oncogenes which promote growth and tumor suppressor genes like RB and p53 which are inactivated, allowing uncontrolled cell division.
- Epidemiology factors in cancer incidence and risk including both modifiable (diet,
Cellular injury and cell death can occur through several mechanisms:
1. Reversible injury may occur when cells are stressed but can still adapt through changes like swelling. Irreversible injury leads to cell death.
2. Necrosis is caused by severe damage where cell contents leak out. Apoptosis is a programmed form of cell death where the cell dismantles itself. Autophagy is a process where cells digest their own components.
3. The causes of cellular injury include hypoxia, physical and chemical agents, infectious agents, immunological reactions, and genetic or nutritional factors. Cell death is identifiable through morphology changes in microscopy.
Reversible cell injury results in cellular swelling and fatty change due to failure of ion pumps and appearance of lipid vacuoles. If injury persists, irreversible changes occur like membrane damage, mitochondrial damage, calcium influx, and reactive oxygen species accumulation leading to cell death by necrosis or apoptosis. Necrosis involves loss of membrane integrity while apoptosis is a regulated pathway of cell fragmentation and phagocytosis.
Cell injury can be reversible or irreversible, leading to cell death. Reversible injury causes pathological changes that can be reversed when the stressor is removed, while irreversible injury causes permanent changes and cell death. Cell injury is caused by various stressors like hypoxia, physical/chemical agents, microbiological agents, genetic defects, and nutritional imbalances. The key targets of injury are the mitochondria, cell membrane, proteins, cytoskeleton, and DNA. Injury disrupts cellular energy production and increases reactive oxygen species, calcium influx, and damage to membranes and DNA/proteins. This can lead to either reversible injury or the irreversible processes of necrosis or apoptosis.
Necrosis is cell death caused by external factors like lack of oxygen, toxins, burns or trauma. There are several types of necrosis including coagulative where tissue structure is preserved, liquefactive where cells are digested, and gangrenous which often involves bacterial infection. Necrotic cells appear eosinophilic on staining and show features like nuclear dissolution or fragmentation. Clinical signs include pain, swelling and spreading skin redness.
CONTENTS,
Introduction
Necrosis
Fates of necrotic cells
Patterns of tissue necrosis
Causes of cell injury
The biomechanism of cell injury
Clinicopathological correlations; examples of cell injury and necrosis
Apoptosis
Causes of apoptosis
Apoptosis in physiologic conditions
Apoptosis in pathologic conditions
Mechanism of Apoptosis
The Mitochondrial pathway of Apoptosis
The Death receptor pathway of Apoptosis
Clearance of Apoptotic cells
Examples of Apoptosis
Summary
References
Cell injury can result from various causes like hypoxia, infections, chemicals, or genetic abnormalities. Injured cells may adapt, die through necrosis or apoptosis, or experience reversible injury. Necrosis is unprogrammed cell death where the cell loses membrane integrity and undergoes physical changes like swelling and nuclear fragmentation. Apoptosis is programmed cell death where the cell remains intact until phagocytosis in a non-inflammatory manner. Different types of necrosis include coagulative, liquefactive, caseous, and gangrenous necrosis.
This document discusses various causes of cell injury and death, including oxygen deprivation, physical agents, chemicals, infectious agents, immune reactions, genetic defects, and nutritional imbalances. It describes the morphological changes that occur in reversible cell injury, including swelling and fatty change, as well as the changes that characterize irreversible injury or necrosis, such as increased eosinophilia, loss of structure, and membrane breakdown. Different patterns of tissue necrosis are also outlined, such as coagulative, liquefactive, gangrenous, and caseous necrosis.
This document discusses various causes of cell injury and death, including oxygen deprivation, physical agents, chemicals, infectious agents, immune reactions, genetic defects, and nutritional imbalances. It describes the morphological changes that occur in reversible cell injury, including swelling and fatty change, as well as irreversible cell injury known as necrosis. Necrosis results in loss of cell integrity and contents. The document outlines different patterns of tissue necrosis, such as coagulative, liquefactive, gangrenous, caseous, and fibrinoid necrosis.
Cell injury, apoptosis and necrosis are described. Cell injury results from disruption of cellular components maintaining viability and can be reversible, lead to adaptation, or cell death. Necrosis is accidental cell death resulting from external factors like ischemia, toxins or radiation. It is characterized by cellular swelling, membrane rupture and nuclear changes like karyorrhexis. Apoptosis is programmed cell death important in development and homeostasis, involving nuclear condensation and fragmentation followed by phagocytosis without inflammation. Different types of necrosis include coagulative, liquefactive, caseous and gangrenous necrosis.
Cell injury and death can occur through two main processes: necrosis and apoptosis. Necrosis is unprogrammed cell death that results from external factors disrupting cellular homeostasis, leading to membrane damage and cellular contents leaking into surrounding tissues. The cell loses its normal structure. Apoptosis is programmed cell death that occurs as part of normal development or in response to cellular damage, and involves nuclear fragmentation and formation of apoptotic bodies that are phagocytosed without inducing inflammation. Necrosis can take various forms depending on the cause and extent of injury, such as coagulative, liquefactive, caseous or gangrenous necrosis. Cell injury precedes cell death and involves disruption of ATP production, calcium homeostasis and cellular
Cell injury occurs when cells are exposed to injurious agents and can be reversible or irreversible depending on the severity and persistence of the stimulus. There are two main types of cell death: necrosis, which is unregulated cell lysis causing inflammation, and apoptosis, which is a regulated and programmed form of cell death. Early changes in cell injury are reversible but persistent injury leads to irreversible changes and ultimately cell death through necrosis or apoptosis.
Cell injury can occur when cells cannot adapt to environmental changes or stresses exceed adaptive responses, leading initially to reversible injury and then irreversible injury causing cell death. Reversible injury involves pathological changes that can be reversed when the stress is removed, while irreversible injury causes permanent changes and cell death. Common causes of cell injury include hypoxia, ischemia, physical and chemical agents, microbiological factors, genetic defects, and nutritional imbalances. The degree and duration of stress determines if injury is reversible or irreversible.
This document describes patterns of acute cell injury, including reversible and irreversible injury. Reversible injury includes cellular swelling and fatty change. Irreversible injury results in cell death through either necrosis or apoptosis. Necrosis is unprogrammed cell death that results from external factors and leads to inflammation. Apoptosis is programmed cell death that occurs physiologically during development and pathologically to remove damaged cells, resulting in cell shrinkage and fragmentation without inflammation.
Necrosis refers to cell death and the morphological changes that follow. There are several types of necrosis that can occur depending on the mechanism of cell death, including coagulative, liquefactive, caseous, and gangrenous necrosis. Microscopic examination of necrotic tissue shows features like loss of nuclei, increased eosinophilic staining of cytoplasm, and loss of normal tissue architecture.
Necrosis refers to cell death and the morphological changes that follow. There are several types of necrosis that can occur depending on the mechanism of cell death, including coagulative, liquefactive, caseous, and gangrenous necrosis. Coagulative necrosis is the most common type and results from ischemia, where the architecture of dead tissue is preserved for weeks before being phagocytosed.
This document discusses cell death and necrosis. It begins by introducing cell injury and defining it as stresses that cells encounter internally and externally. There are two main types of cell death - necrosis and apoptosis. Necrosis is the irreversible cell injury and death that occurs when damage becomes too severe for the cell to recover. Apoptosis is programmed cell death that is important for normal physiology. The document further explores the mechanisms, morphology, and types of necrosis including coagulative, liquefactive, caseous, fat, and fibrinoid necrosis. It also discusses the mechanisms, initiators, regulators and roles of apoptosis. Gangrene is defined as a condition caused by critically insufficient blood supply that results in cell death.
Cell injury and death can occur through various mechanisms including hypoxia, physical or chemical insults, and microbial or immunological agents. The cellular response to injury depends on the cell type, extent, and type of injury. Initial responses include cellular adaptation, subcellular changes, or intracellular accumulations. Injury may result in reversible or irreversible cell damage and cell death. Irreversible injury is characterized by mitochondrial dysfunction and membrane damage, leading to necrosis or apoptosis. Different patterns of necrosis include coagulative, liquefactive, caseous, and gangrenous necrosis.
Cell injury occurs when cells are exposed to harmful external stress that exceeds their adaptive responses. It is a reversible process up to a certain point. The main types of cell adaptations include hypertrophy, hyperplasia, atrophy, and metaplasia. Causes of cell injury include hypoxia, toxins, infections, immunologic reactions, and genetic abnormalities. Morphological changes in reversible injury include swelling and vacuolization. Necrosis and apoptosis are the two main mechanisms of cell death. Necrosis is unprogrammed cell death from membrane disruption while apoptosis is programmed cell death where the cell degrades itself.
Cell injury can be reversible or irreversible. Reversible cell injury involves cell swelling and changes to organelles. Irreversible injury leads to cytoplasmic and nuclear changes, as well as damage to mitochondria and plasma membranes. Failure of ATP production in mitochondria during ischemia or hypoxia can cause failure of the sodium-potassium pump, leading to intracellular sodium and calcium accumulation and cellular swelling. There are several types of cell necrosis characterized by different morphological features, including coagulative, liquefactive, caseous, fat and fibrinoid necrosis.
This document discusses reversible and irreversible cell injury. Reversible injury involves stress responses that activate heat shock proteins to repair damaged cells. If repair is not possible, injury becomes irreversible and cells die through either necrosis or apoptosis. Necrosis is accidental cell death involving enzymatic digestion and protein denaturation. There are several types of necrosis described by the predominant process and affected tissues. Irreversible injury results in loss of integrated cell functions and structures.
Encephalitis is an inflammation of the brain that is usually caused by a viral infection. It can cause symptoms like fever, headache, vomiting, and confusion. While most cases are mild, encephalitis can sometimes be life-threatening. The document discusses the types, causes, risk factors, diagnosis, treatment, and prevention of encephalitis.
The document defines phakomatoses as multisystem disorders that affect the central nervous system, eyes, and skin with characteristic lesions and hamartomas. Common phakomatoses include neurofibromatosis types 1 and 2, tuberous sclerosis, Von Hippel-Lindau syndrome, Sturge-Weber syndrome, and Wyburn-Mason syndrome. Neurofibromatosis type 1 is characterized by café au lait spots and Lisch nodules on the iris. Tuberous sclerosis causes retinal astrocytic hamartomas and adenoma sebaceum skin lesions. Von Hippel-Lindau syndrome features retinal capillary hemangioblastomas and central
The document defines phakomatoses as multisystem disorders affecting the central nervous system, eyes, and skin with characteristic lesions and hamartomas. Common phakomatoses include neurofibromatosis types 1 and 2, tuberous sclerosis, Von Hippel-Lindau syndrome, Sturge-Weber syndrome, and Wyburn-Mason syndrome. Neurofibromatosis type 1 is characterized by café au lait spots and Lisch nodules on the iris. Tuberous sclerosis causes retinal astrocytic hamartomas and adenoma sebaceum skin lesions. Von Hippel-Lindau syndrome features retinal capillary hemangioblastomas and central nervous
This document discusses lysosomal storage disorders, which are a group of rare inherited disorders caused by deficiencies in lysosomal enzymes. Specific disorders discussed include Gaucher disease, the most common lysosomal storage disease caused by glucocerebrosidase deficiency; Tay-Sachs disease caused by hexosaminidase A deficiency; Niemann-Pick disease types A and B caused by sphingomyelinase deficiency; and Fabry disease caused by alpha-galactosidase A deficiency. Signs and symptoms as well as characteristics of each disease are described.
1) Systemic sclerosis is a disorder of connective tissue that causes hardening and tightening of the skin. It occurs more often in females and peaks between ages 40-50.
2) There are two main types: limited cutaneous which mainly affects the skin, and diffuse cutaneous which has more severe internal organ involvement.
3) Symptoms include thickened skin, especially on the hands, as well as Raynaud's phenomenon and potential lung, heart, kidney, or gastrointestinal complications. Management focuses on treating specific organ involvement and symptoms.
The research team reviewed charts of 351 systemic sclerosis patients from UC Davis to analyze differences in disease manifestations and outcomes by race/ethnicity. They identified 46 patients that met inclusion criteria, 45 of which were included in the analysis. Preliminary results found higher rates of mortality, pulmonary hypertension, and interstitial lung disease in black patients compared to other groups. However, the differences were not statistically significant likely due to small sample sizes. The analysis also found unique serological and clinical features across racial groups.
Hypertension, also known as high blood pressure, is defined as a systolic blood pressure of 140 mmHg or higher and/or a diastolic blood pressure of 90 mmHg or higher. It is classified into prehypertension, stage I hypertension, and stage II hypertension based on blood pressure levels. Hypertension can be primary (essential) or secondary to other medical conditions. Risk factors include increasing age, family history, obesity, smoking, excessive alcohol use, and stress. Treatment involves lifestyle modifications like diet, exercise, and weight loss as well as pharmacological therapy using different classes of antihypertensive medications.
Cell death can occur through two main processes: necrosis and apoptosis. Necrosis is unregulated cell death caused by external factors like trauma or toxins. It involves the premature death of cells and tissue damage. Apoptosis is a tightly regulated form of programmed cell death that eliminates unnecessary or potentially dangerous cells. It involves changes to the cell like nuclear fragmentation, blebbing of the cell membrane, and formation of apoptotic bodies that are then cleared by phagocytes without inducing inflammation. Apoptosis plays an important role in development, homeostasis, and eliminating infected or damaged cells.
Entamoeba histolytica is a protozoan parasite that can cause amebiasis in humans. It has a worldwide distribution but is most common in tropical and subtropical areas. The infective stage is the cyst, which is ingested and undergoes excystation in the small intestine. Trophozoites then colonize the large intestine where they can invade the mucosa and cause lesions. In some cases, the parasite can spread to other organs and cause abscesses. Symptoms of infection range from abdominal discomfort to dysentery. Diagnosis involves examination of stool samples while treatment typically involves metronidazole.
Ameba are protozoa that use pseudopodia or cytoplasmic flow for locomotion. Some ameba species are harmless while others like Entamoeba histolytica are pathogenic parasites of humans. E. histolytica infects 10% of the world's population but only causes clinical signs in 3%. It has a life cycle involving an infective cyst stage and an active trophozoite stage. Trophozoites can cause intestinal lesions and abscesses in the liver, lungs or brain. Symptoms include abdominal pain and dysentery. Diagnosis involves fecal analysis and treatment is usually with metronidazole.
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2. Cell injury results when
cells are stressed and
can no longer adapt
Injury may progress
through a reversible
stage
3. Reduced oxidative phosphorylation with
resultant depletion of energy stores in the
form of adenosine triphosphate (ATP)
Cellular swelling caused by changes in ion
concentrations and water influx
Reversible Cell Injury
4. Cell Death
Necrosis- pathologic
Damage to membranes is severe, lysosomal enzymes enter
the cytoplasm and digest the cell, and cellular contents leak
out
Apoptosis- normal and pathologic
DNA or proteins are damaged beyond repair, the cell kills
itself characterized by nuclear dissolution, fragmentation of
the cell without complete loss of membrane integrity
Autophagy- normal and pathologic
5. Oxygen Deprivation
Hypoxia is a deficiency of oxygen that can result in a reduction in aerobic oxidative
respiration. Extremely important common cause of cell injury/cell death.
Causes include reduced blood flow (ischemia), inadequate oxygenation of the
blood, decreased blood oxygen-carrying capacity.
Physical Agents
Mechanical trauma, extremes of temperature (burns and deep cold), sudden
changes in atmospheric pressure, radiation, and electric shock.
Chemical Agents and Drugs
Infectious Agents
Immunologic Reactions
Genetic Derangements
Nutritional Imbalances
Protein-calorie and/or vitamin deficiencies. Nutritional excesses (overnutrition)
Causes of Cell Injury
10. Normal kidney tubules
• Epithelial cells stain
evenly pink
(eosinophilic) in
cytoplasm, with
purple, basophilic,
nucleic acids
confined to the nuclei
• Apical surfaces are
ciliated
• Interstitia not
infiltrated with
immune cells nor
congested with
proteins
11. Swollen kidney tubules
• Increased eosinophilic
staining
• Decreased basophilic
staining (RNA)
• Plasma membrane
rounding, blebbing,
loss of cilia, due to
loss of connections
with cytoskeleton
• Integrity of tubules
degrading, but
basement membranes
intact
• Nuclei largely intact,
slightly narrowed,
pyknotic
13. Reversible damage – cellular swelling
Cellular swelling (synonyms: hydropic change, vacuolar degeneration, cellular edema) is an acute reversible
change resulting as a response to nonlethal injuries. It is an intracytoplasmic accumulation of water due to
incapacity of the cells to maintain the ionic and fluid homeostasis. It is easy to be observed in parenchymal
organs : liver (hepatitis, hypoxia), kidney (shock), myocardium (hypoxia, phosphate intoxication). It may be
local or diffuse, affecting the whole organ.
14. Reversible damage – fatty change
Intracellular accumulations of a variety of materials can occur in response to
cellular injury. Here is fatty metamorphosis (fatty change) of the liver in which
deranged lipoprotein transport from injury (most often alcoholism) leads to
accumulation of lipid in the cytoplasm of hepatocytes.
15. Necrotic kidney tubules
• Cellular
fragmentation
• Loss and fading of
nuclei--karyolysis
• Burst membranes
• Loss of tissue
architecture
16. The morphologic appearance of necrosis is the result of
denaturation of intracellular proteins and enzymatic digestion.
Necrotic cells are unable to maintain membrane integrity and
their contents often leak out, a process that may elicit
inflammation in the surrounding tissue.
The enzymes that digest the necrotic cell are derived from the
lysosomes of the dying cells themselves and from the
lysosomes of leukocytes that are called in as part of the
inflammatory reaction.
Digestion of cellular contents and the host response may take
hours to develop. The earliest histologic evidence of necrosis
may not become apparent until 4 to 12 hours.
Necrosis
17.
18.
19. Increased eosinophilia in hematoxylin and eosin (H & E) stains,
attributable in part to the loss of cytoplasmic RNA (which binds the blue
dye, hematoxylin) and in part to denatured cytoplasmic proteins (which
bind the red dye, eosin).
When enzymes have digested the cytoplasmic organelles, the cytoplasm
becomes vacuolated and appears moth-eaten.
Dead cells may be replaced by large, whorled phospholipid masses
called myelin figures that are derived from damaged cell membranes.
These phospholipid precipitates are then either phagocytosed by other
cells or further degraded into fatty acids; calcification of such fatty acid
residues results in the generation of calcium soaps. Thus, the dead cells
may ultimately become calcified.
Necrosis- cytoplasm
20. Nuclear changes appear in one of three patterns
Karyolysis, the basophilia of the chromatin fades which appears to
reflect loss of DNA because of enzymatic degradation by due to
endonucleases.
Pyknosis, characterized by nuclear shrinkage and increased
basophilia.
Karyorrhexis, the pyknotic nucleus undergoes fragmentation. With the
passage of time (a day or two), the nucleus
in the necrotic cell totally disappears.
Necrosis- nucleus
http://www.vetmed.vt.edu/education/Curriculum/VM830
4/vet%20pathology/CASES/CELLINJURY2/karyorrhexd
iag%20copy.JPG
21. When large numbers of cells die the tissue or
organ is said to be necrotic
Necrosis of tissues has several
morphologically distinct patterns, which are
important to recognize because they may
provide clues about the underlying cause.
The terms that describe these patterns are
somewhat outmoded, they are used often and
their implications are understood by
pathologists and clinicians.
Patterns of Tissue Necrosis
23. Architecture of dead tissues is
preserved for a span of at least some
days.
Tissues exhibit a firm texture
Injury denatures proteins and enzymes
blocking proteolysis of the dead cells;
Eosinophilic, anucleate cells may
persist for days or weeks.
Ultimately the necrotic cells are
removed by phagocytosis of the
cellular debris by infiltrating
leukocytes.
Coagulative Necrosis
24.
25. Coagulative necrosis—kidney infarction
This is the typical pattern with ischemia and infarction (loss of
blood supply and resultant tissue anoxia). Here, there is a wedge-
shaped pale area of coagulative necrosis (infarction) in the renal
cortex of the kidney. Microscopically, the renal cortex has
undergone anoxic injury at the left so that the cells appear pale
and ghost-like. There is a hemorrhagic zone in the middle where
the cells are dying or have not quite died, and then normal renal
parenchyma at the far right.
26. Coagulative necrosis—myocardial infarction
Here is myocardium in which the cells are
dying as a result of ischemic injury from
coronary artery occlusion. This is early in
the process of necrosis. The nuclei of the
myocardial fibers are being lost. The
cytoplasm is losing its structure, because
no well-defined cross-striations are seen.
http://bcrc.bio.umass.edu/histology/files/images/SZR
1.preview.jpg
http://library.med.utah.edu/WebPath/CINJHT
ML/CINJ013.html
27. Digestion of the dead
Transformation of the tissue into a
liquid viscous mass.
The necrotic material is frequently
creamy yellow because of the
presence of dead leukocytes and is
called pus.
Liquefactive Necrosis
http://wikidoc.org/images/c/c8/Liquefactive_necr
osis_Lung_7.jpg
28. Not a specific pattern.
Term is commonly used in clinical
practice.
Usually applied to a limb, generally the
lower leg, that has lost its blood supply
and has undergone, typically,
coagulative necrosis
Gangrenous Necrosis
http://meded.ucsd.edu/clinicalimg/skin_gangrene_dic.jpg
Sepsis induced DIC has led to extensive arterial
thrombosis, resulting in
profound tissue death.
http://www.microscopy-uk.org.uk/mag/imgaug02/HistPaper01_Fig2.jpg
WebPath/CINJHTML/CINJ051.htm
29. “Caseous” (cheeselike) is derived from
the friable white appearance of the
area of necrosis
Necrotic area appears as a collection
of fragmented or lysed cells and
amorphous granular debris enclosed
within a distinctive inflammatory
border; this appearance is
characteristic of a focus of
inflammation known as a granuloma.
Caseous Necrosis
http://granuloma.hom
estead.com/files/gran
uloma_apoptotic2.jpg
http://www.me
d.nus.edu.sg/
path/images/t
b-myco.jpg
30. Not a specific pattern
Focal areas of fat destruction, typically
resulting from release of activated
pancreatic lipases into the substance
of the pancreas and the peritoneal
cavity.
Lipases split the triglyceride esters
contained within fat cells. Free fatty
acids can combine with calcium to
produce grossly visible chalky-white
areas (fat saponification).
Fat Necrosis
http://pancreas.org/wp-
content/uploads/nl-pancreas-cells.jpg
31. Usually seen in immune reactions
involving blood vessels.
Deposits of “immune complexes,”
together with fibrin that has leaked out
of vessels.
Bright pink and amorphous
appearance in H&E stains, called
“fibrinoid” (fibrin-like) by pathologists.
Fibrinoid Necrosis
33. Energy depletion
• Inhibition of oxidative phosphorylation
• [ATP] decreases
• Small changes, 5 - 10%, are sufficient to limit the
Na/K-ATPase and Ca/Mg ATPase
• Glycolytic capacity (glycogen stores) protects
from ATP depletion but leads to acidification
– Plasma and ER membranes swell
– Enzyme kinetics change; proteins begin to denature
– Chromatin clumps
• Denatured proteins either coagulate resulting in
necrosis or bind HSPs triggering apoptosis
35. Intracellular, cytosolic [Ca++] as
many as 4 orders of magnitude
lower than extracellular or
organellar (ER, SR, Mt)
Mitochondrial damage and ER
swelling releases Ca++ to
cytosol
Hydrolytic enzymes activated
Apoptosis may be activated
Necrosis occurs
Calcium Flux
36.
37.
38. ROS and free radicals
• Hydroxyl radicals and hydrogen may be split
from water by ionizing radiation
• Superoxide radicals, hydrogen peroxide, lipid
peroxides normally present in small amounts
– Neutralized by catalase or glutathione peroxidase
• ROS created and released by neutrophils in
response to microbial infection
• Toxic chemicals natively, or after activation by
P450 redox in liver or kidney, may result in free
radicals
• ROS initiate chain reaction of lipid peroxidation
in membranes
42. Loss of ER Homeostasis
http://www.sciencedirect.com/science/article/pii/S1550413112001027
43.
44.
45.
46. Apoptosis
• Programmed cell death
– Especially during fetal development
– In response to hormonal cycles (e.g.
endometrium)
– Normal turnover in proliferating tissues (e.g.
intestinal epithelium)
• Cells shrink, not swell
• Nuclei condense and DNA fragments
• Cells fragment into membrane-bound bits
• Bits are phagocytosed by macrophages
47.
48. Apoptotic fetal thymus
In this fetal thymus there is involution of
thymic lymphocytes by the mechanism
of apoptosis. In this case, it is an
orderly process and part of normal
immune system maturation. Individual
cells fragment and are consumed by
phagocytes to give the appearance of
clear spaces filled with cellular debris.
Apoptosis is controlled by many
mechanisms. Genes such as BCL-2
are turned off and Bax genes turned
on. Intracellular proteolytic enzymes
called caspases produce much cellular
breakdown.
49.
50. Apoptotic liver
Apoptosis is a more orderly process of
cell death. Apoptosis is individual cell
necrosis, not simultaneous localized
necrosis of large numbers of cells. In
this example, hepatocytes are dying
individually (arrows) from injury through
infection by viral hepatitis. The
apoptotic cells are enlarged, pink from
loss of cytoplasmic detail, and without
nuclei. The cell nucleus and cytoplasm
become fragmented as enzymes such
as caspases destroy cellular
components.