Intracellular Accumulations: Causes, Types, Examples, and Clinical Significance

Intracellular Accumulations: Causes, Types, Examples, and Clinical Significance

pediagenosis    September 06, 2026    Comment   

Intracellular Accumulations.

Intracellular accumulations represent the buildup of substances that cells cannot immediately use or eliminate. The substances may accumulate in the cytoplasm (frequently in the lysosomes) or in the nucleus. In some cases the accumulation may be an abnormal substance that the cell has produced, and in other cases the cell may be storing exogenous materials or products of pathologic processes occurring elsewhere in the body. An example would be the accumulation of beta amyloid fragments, which progress to a skeletal muscle disorder called myositis. These substances may  accumulate  transiently  or  permanently, and they may be harmless or, in some cases, toxic.

Reversible Cell Injury and Cell Death

Reversible Cell Injury and Cell Death

pediagenosis    February 19, 2023    Comment   

Reversible Cell Injury and Cell Death.

The mechanisms of cell injury can produce sublethal and reversible cellular damage or lead to irreversible injury with cell destruction or death (Fig.  5.8). Celldestruction and removal can involve one of two mechanisms:

•       Apoptosis, which is designed to remove injured or worn-out cells

•       Cell death or necrosis, which occurs in irreversibly damaged cells

Causes of Cell Injury

Causes of Cell Injury

pediagenosis    February 19, 2023    Comment   

Causes of Cell Injury.

Cell damage can occur in many ways. For purposes of discussion, the ways by which cells are injured have been grouped into five categories:

•       Injury from physical agents

•       Radiation injury

•       Chemical injury

•       Injury from biologic agents

•       Injury from nutritional imbalances

Injury from Physical Agents

Physical agents responsible for cell and tissue injury include mechanical forces, extremes of temperature, and electrical forces. They are common causes of injuries due to environmental exposure, occupational and transportation accidents, and physical violence and assault.

Sideroblastic Anaemia

Sideroblastic Anaemia

pediagenosis    May 29, 2021    Comment   

Sideroblastic Anaemia

This is a refractory anaemia defined by the presence of many pathological ring sideroblasts in the bone marrow (Fig. 3.14). These are abnormal erythroblasts containing numerous iron granules arranged in a ring or collar around the nucleus instead of the few randomly distributed iron granules seen when normal erythroblasts are stained for iron. There is also usually erythroid hyperplasia with ineffective erythropoiesis. Sideroblastic anaemia is diagnosed when 15% or more of marrow erythroblasts are ring sideroblasts. They can be found at lower numbers in a variety of haematological conditions.

Figure 3.14 Ring sideroblasts with a perinuclear ring of iron granules in sideroblastic anaemia.

Sideroblastic anaemia is classified into different types (Table 3.8) and the common link is a defect in haem synthesis. In the hereditary forms the anaemia is usually characterized by a markedly hypochromic and microcytic blood picture. The most common mutations are in the ALA‐S gene which is on the X chromosome. Pyridoxal‐6‐phosphate is a coenzyme for ALA‐S. Other rare types include an X‐linked disease with spinocerebellar degeneration and ataxia, mitochondrial defects (e.g. Pearson’s syndrome when there is also pancreatic insufficiency), thiamine‐responsive and other autosomal defects. The much more common form is refractory anaemia with ring sideroblasts, which is a subtype of myelodysplasia (see Chapter 16). Acquired reversible forms may be due to alcohol, lead and drugs, e.g. isoniazid.

Lead Poisoning

Lead Poisoning

pediagenosis    May 29, 2021    Comment   

Lead Poisoning

Figure 2.7  Haemoglobin synthesis in the developing red cell. The mitochondria are the main sites of protoporphyrin synthesis, iron (Fe) is supplied from circulating transferrin; globin chains are synthesized on ribosomes. δ‐ALA, δ‐aminolaevulinic acid; CoA, coenzyme A.

       Lead inhibits both haem and globin synthesis at a number of points. In addition it interferes with the breakdown of RNA by inhibiting the enzyme pyrimidine 5′ nucleotidase, causing accumulation of denatured RNA in red cells, the RNA giving an appearance called basophilic stippling on the ordinary (Romanowsky) stain (see Fig. 2.17). 

Differential Diagnosis Of Hypochromic

Differential Diagnosis Of Hypochromic

pediagenosis    May 29, 2021    Comment   

Differential Diagnosis Of Hypochromic

Table 3.7 Laboratory diagnosis of a hypochromic anaemia.

anaemia

Table 3.7 lists the laboratory investigations that may be neces­ sary. The clinical history is particularly important as the source of the haemorrhage leading to iron deficiency or the presence of a chronic disease may be revealed. The country of origin and the family history may suggest a possible diagnosis of thalassaemia or other genetic defect of haemoglobin. Physical examination may also be helpful in determining a site of haemorrhage, features of a chronic inflammatory or malignant disease, koilonychia or, in some haemoglobinopathies, an enlarged spleen or bony deformities.

Anaemia Of Chronic Disorders

Anaemia Of Chronic Disorders

pediagenosis    November 15, 2019    Comment   

Anaemia Of Chronic Disorders

One of the most common anaemias occurs in patients with a variety of chronic inflammatory and malignant diseases (Table 3.6). The characteristic features are:

1.    Normochromic, normocytic or mildly hypochromic (MCV rarely <75 fL) indices and red cell morphology.

2.    Mild and non‐progressive anaemia (haemoglobin rarely <90 g/L) – the severity being related to the severity of the disease.

3.    Both the serum iron and TIBC are reduced.

4.    The serum ferritin is normal or raised.

5.  Bone marrow storage (reticuloendothelial) iron is normal but erythroblast iron is reduced (Table 3.7).

Iron Refractory Iron Deficency Anaemia (IRIDA)

Iron Refractory Iron Deficency Anaemia (IRIDA)

pediagenosis    September 03, 2019    Comment   

Iron Refractory Iron Deficency Anaemia

(IRIDA)

Iron Deficiency

Iron Deficiency

pediagenosis    September 03, 2019    Comment   

Iron Deficiency

Clinical features

When iron deficiency is developing, the reticuloendothelial stores (haemosiderin and ferritin) become completely depleted before anaemia occurs (Fig. 3.6). As the condition develops, the patient may show the general symptoms and signs of anaemia (see p. 20) and also a painless glossitis, angular stomatitis, brittle, ridged or spoon nails (koilonychia) (Fig. 3.7) and unusual dietary cravings (pica). The cause of the epithelial cell changes is not clear but may be related to reduction of iron‐containing enzymes. In children, iron deficiency is particularly significant as it can cause irritability, poor cognitive function and a decline in psychomotor development. There is also evidence that oral or parenteral iron may reduce fatigue in iron‐deficient (low serum ferritin) non‐anaemic women.

Nutritional And Metabolic Aspects Of Iron

Nutritional And Metabolic Aspects Of Iron

pediagenosis    May 30, 2019    Comment   

Nutritional And Metabolic Aspects Of Iron

Body iron distribution and transport

The transport and storage of iron is largely mediated by three proteins: transferrin, transferrin receptor 1 (TfR1) and ferritin.

Anaemia

Anaemia

pediagenosis    May 30, 2019    Comment   

Anaemia

This is defined as a reduction in the haemoglobin concentration of the blood below normal for age and sex (Table 2.4). Although normal values can vary between laboratories, typical values would be less than 135 g/L in adult males and less than 115 g/L in adult females (Fig. 2.13). From the age of 2 years to puberty, less than 110 g/L indicates anaemia. As newborn infants have a high haemoglobin level, 140 g/L is taken as the lower limit at birth (Fig. 2.13).

The Red Cell

The Red Cell

pediagenosis    May 30, 2019    Comment   

The Red Cell

In order to carry haemoglobin into close contact with the tissues and for successful gaseous exchange, the red cell, 8 μm in diameter, must be able: to pass repeatedly through the microcirculation whose minimum diameter is 3.5 μm, to maintain haemoglobin in a reduced (ferrous) state and to maintain osmotic equilibrium despite the high concentration of protein (haemoglobin) in the cell. A single journey round the body takes 20 seconds and its total journey throughout its 120‐day lifespan has been estimated to be 480 km (300 miles). To fulfil these functions, the cell is a flexible biconcave disc with an ability to generate energy as adenosine triphosphate (ATP) by the anaerobic glycolytic (Embden–Meyerhof ) pathway (Fig. 2.11) and to generate reducing power as nicotinamide adenine dinucleotide (NADH) by this pathway and as reduced nicotinamide adenine dinucleotide phosphate (NADPH) by the hexose monophosphate shunt (see Fig. 6.6).

Haemoglobin

Haemoglobin

pediagenosis    May 15, 2019    Comment   

Haemoglobin

Haemoglobin Synthesis

The main function of red cells is to carry O2 to the tissues and to return carbon dioxide (CO2) from the tissues to the lungs. In order to achieve this gaseous exchange they contain the specialized protein haemoglobin. Each molecule of normal adult haemoglobin A (Hb A) (the dominant haemoglobin in blood after the age of 3–6 months) consists of four polypeptide chains, α2β2, each with its own haem group. Normal adult blood also contains small quantities of two other haemoglobins: Hb F and Hb A2. These also contain α chains, but with γ and δ chains, respectively, instead of β (Table 2.3). The synthesis of the various globin chains in the fetus and adult is discussed in more detail in Chapter 7.

Erythropoietin

Erythropoietin

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Erythropoietin

Erythropoiesis is regulated by the hormone erythropoietin. Erythropoietin is a heavily glycosylated polypeptide. Normally, 90% of the hormone is produced in the peritubular interstitial cells of the kidney and 10% in the liver and elsewhere. There are no preformed stores and the stimulus to erythropoietin production is the oxygen (O₂) tension in the tissues of the kidney (Fig. 2.5). Hypoxia induces synthesis of hypoxia‐inducible factors (HIF‐1α and β), which stimulate erythropoietin production and also new vessel formation and transferrin receptor synthesis, and reduces hepcidin synthesis, increasing iron absorption. Von Hippel‐Lindau (VHL) protein breaks down HIFs and PHD2 hydroxylates HIF‐1α allowing VHL binding (Fig. 2.5). Abnormalities in these proteins may cause polycythaemia (see Chapter 15).

Blood Cells

Blood Cells

pediagenosis    May 15, 2019    Comment   

Blood Cells

All the circulating blood cells derive from pluripotential stem cells in the marrow. They divide into three main types. The most numerous are red cells which are specialized for carriage of oxygen from the lungs to the tissues and of carbon dioxide in the reverse direction (Table 2.1). They have a 4‐ month lifespan, whereas the smallest cells, platelets involved in haemostasis, circulate for only 10 days. The white cells are made up of four types of phagocyte, neutrophils, eosinophils, basophils and monocytes, which protect against bacterial and fungal infections, and of lymphocytes, which include B cells, involved in antibody production, and T cells (CD4 helper and CD8 suppressor), concerned with the immune response and in protection against viruses and other foreign cells. White cells have a wide range of lifespan (Table 2.1).

Apoptosis

Apoptosis

pediagenosis    September 19, 2018    Comment   

Apoptosis

Apoptosis (programmed cell death) is a regulated process of physiological cell death in which individual cells are triggered to activate intracellular proteins that lead to the death of the cell. Morphologically it is characterized by cell shrinkage, condensation of the nuclear chromatin, fragmentation of the nucleus and cleavage of DNA at internucleosomal sites. It is an important process for maintaining tissue homeostasis in haemopoiesis and lymphocyte development.

Epigenetics

Epigenetics

pediagenosis    September 19, 2018    Comment   

Epigenetics

This refers to changes in DNA and chromatin that affect gene expression other than those that affect DNA sequence.

Transcription Factors

Transcription Factors

pediagenosis    September 19, 2018    Comment   

Transcription Factors

Transcription factors regulate gene expression by controlling the transcription of specific genes or gene families (Fig. 1.8). Typically, they contain at least two domains: a DNA‐binding domain, such as a leucine zipper or helix–loop–helix motif which binds to a specific DNA sequence, and an activation domain, which contributes to assembly of the transcription complex at a gene promoter. Mutation, deletion or translocation of transcription factors underlie many cases of haematological neoplasms (see Chapter 11).

The Cell Cycle

The Cell Cycle

pediagenosis    September 19, 2018    Comment   

The Cell Cycle

The cell division cycle, generally known simply as the cell cycle, is a complex process that lies at the heart of haemopoiesis. Dysregulation of cell proliferation is also the key to the development of malignant disease. The duration of the cell cycle is variable between different tissues but the basic principles remain constant. The cycle is divided into the mitotic phase (M phase), during which the cell physically divides, and interphase, during which the chromosomes are duplicated and cell growth occurs prior to division (Fig. 1.7). The M phase is further partitioned into classical mitosis, in which nuclear division is accomplished, and cytokinesis, in which cell fission occurs.

Adhesion Molecules

Adhesion Molecules

pediagenosis    September 19, 2018    Comment   

Adhesion Molecules

A large family of glycoprotein molecules termed adhesion molecules mediate the attachment of marrow precursors, leucocytes and platelets to various components of the extracellular matrix, to endothelium, to other surfaces and to each other. The adhesion molecules on the surface of leucocytes are termed receptors and these interact with proteins termed ligands on the surface of target cells, e.g. endothelium. The adhesion molecules are important in the development and maintenance of inflammatory and immune responses, and in platelet–vessel wall and leucocyte–vessel wall interactions.