- Published on
Pathology - Sjogren's Syndrome
Sjögren’s syndrome is an autoimmune illness that mostly affects the salivary glands. The primary oral complaint is xerostomia (dry mouth), which can lead to difficulties swallowing, dental caries, and inability to speak continuously. Patients with ocular involvement will commonly complain of a gritty sensation beneath the eyelids, likely from damage of bulbar or corneal conjunctival epithelium due to decreased lacrimation from xerophthalmia (dry eye). The physical findings in this patient are typical, including parotid enlargement. Other possible symptoms include weariness, low-grade fever, myalgias, arthralgias, and Raynaud’s phenomenon. The pathophysiology is a result of exocrine (e.g., salivary, lacrimal) gland invasion by T- and B-cell lymphocytes and B-lymphocyte hyperactivity.
Through a number of biological cascades, T-cells trigger glandular epithelial cell death. Ductal and acinar epithelial cells sustain the continuing immunological reaction by improperly generating proinflammatory cytokines and lymphoattractant chemokines. Patient will often have non–organ-specific autoantibodies including ANA and rheumatoid factor (RF); nevertheless, the presence of anti-Ro/SS-A and anti-La/SS-B autoantibodies is specific for Sjögren’s syndrome.
Treatment is mainly supportive; punctal plugs can be used to minimize tear drainage into the nasolacrimal duct, and regular dental care should be established.
Sjögren’s syndrome is an autoimmune illness that mostly affects the salivary glands. The primary oral complaint is xerostomia (dry mouth), which can lead to difficulties swallowing, dental caries, and inability to speak continuously. Patients with ocular involvement will commonly complain of a gritty sensation beneath the eyelids, likely from damage of bulbar or corneal conjunctival epithelium due to decreased lacrimation from xerophthalmia (dry eye). The physical findings in this patient are typical, including parotid enlargement. Other possible symptoms include weariness, low-grade fever, myalgias, arthralgias, and Raynaud’s phenomenon. The pathophysiology is a result of exocrine (e.g., salivary, lacrimal) gland invasion by T- and B-cell lymphocytes and B-lymphocyte hyperactivity.
Through a number of biological cascades, T-cells trigger glandular epithelial cell death. Ductal and acinar epithelial cells sustain the continuing immunological reaction by improperly generating proinflammatory cytokines and lymphoattractant chemokines. Patient will often have non–organ-specific autoantibodies including ANA and rheumatoid factor (RF); nevertheless, the presence of anti-Ro/SS-A and anti-La/SS-B autoantibodies is specific for Sjögren’s syndrome.
Treatment is mainly supportive; punctal plugs can be used to minimize tear drainage into the nasolacrimal duct, and regular dental care should be established.
- Published on
Pathology - Acute Rejection of Transplant
Acute rejection of transplanted kidney, the most prevalent type of transplant rejection.
The patient will present with indicators of rejection anywhere from days to up to 6 months post-transplant, which may include myalgias, arthralgias, fever, chills, or other organ-related symptoms such as oliguria for a renal transplant. However, organ-specific function laboratory tests may be the only indication that rejection is occurring, requiring constant monitoring of transplant recipients. The mechanism of acute rejection is a type IV cell-mediated hypersensitivity and concurrent type II antibody-mediated hypersensitivity reaction. Although MHC antigen reactivity was screened for in HLA-matching, HLA complex minor histocompatibility antigens on the allograft (speciesspecific transplant) trigger CD4 + T cells in the recipient to produce cytokines and generate adhesion molecules. This results in proliferation and activation of CD8 + T cells, which release perforins leading to cell death, as well as stimulation of host macrophages by IFN-γ. Adhesion molecules facilitate lymphocyte movement, creating graft edema and endothelial cell damage. The autoantibody reaction is driven by B cell development into plasma cells, producing anti-HLA antibodies, resulting to vasculitis or intimal thickening of the graft. Acute rejection can be controlled with immunosuppressive treatment and is generally reversible. Decline in organ function, which happens many months to years after transplant is chronic rejection. Its mechanism is not well known but results in ischemia to tissue and may be a result of repeated episodes of acute rejection.
Acute rejection of transplanted kidney, the most prevalent type of transplant rejection.
The patient will present with indicators of rejection anywhere from days to up to 6 months post-transplant, which may include myalgias, arthralgias, fever, chills, or other organ-related symptoms such as oliguria for a renal transplant. However, organ-specific function laboratory tests may be the only indication that rejection is occurring, requiring constant monitoring of transplant recipients. The mechanism of acute rejection is a type IV cell-mediated hypersensitivity and concurrent type II antibody-mediated hypersensitivity reaction. Although MHC antigen reactivity was screened for in HLA-matching, HLA complex minor histocompatibility antigens on the allograft (speciesspecific transplant) trigger CD4 + T cells in the recipient to produce cytokines and generate adhesion molecules. This results in proliferation and activation of CD8 + T cells, which release perforins leading to cell death, as well as stimulation of host macrophages by IFN-γ. Adhesion molecules facilitate lymphocyte movement, creating graft edema and endothelial cell damage. The autoantibody reaction is driven by B cell development into plasma cells, producing anti-HLA antibodies, resulting to vasculitis or intimal thickening of the graft. Acute rejection can be controlled with immunosuppressive treatment and is generally reversible. Decline in organ function, which happens many months to years after transplant is chronic rejection. Its mechanism is not well known but results in ischemia to tissue and may be a result of repeated episodes of acute rejection.
- Published on
Pathology - Severe Combined Immunodeficiency Disease
SCID occurs from a genetic abnormality in stem cells, resulting in absence of the thymus and T and B lymphocytes. In one-half of patients, an autosomal recessive transmission results in the loss of adenosine deaminase, an enzyme involved in purine catabolism. This leads in an accumulation of hazardous deoxyadenosine triphosphate, blocking ribonucleotide reductase and limiting DNA synthesis and therefore lymphocyte proliferation. In other cases, an X-linked transmission leads in absent gamma chain of the interleukin receptor, slowing lymphocyte growth due to issues with interleukin signaling. These patients will present with recurring bacterial, viral, parasite, and fungal infections at a relatively young age; however, maternal antibodies may delay commencement by a few months. Infections will become quite dangerous and include pneumonia, bacteremia, sepsis, and meningitis. Life span is often very short without treatment; however, early discovery and treatment with gene therapy and bone marrow transplantation can be curative.
SCID occurs from a genetic abnormality in stem cells, resulting in absence of the thymus and T and B lymphocytes. In one-half of patients, an autosomal recessive transmission results in the loss of adenosine deaminase, an enzyme involved in purine catabolism. This leads in an accumulation of hazardous deoxyadenosine triphosphate, blocking ribonucleotide reductase and limiting DNA synthesis and therefore lymphocyte proliferation. In other cases, an X-linked transmission leads in absent gamma chain of the interleukin receptor, slowing lymphocyte growth due to issues with interleukin signaling. These patients will present with recurring bacterial, viral, parasite, and fungal infections at a relatively young age; however, maternal antibodies may delay commencement by a few months. Infections will become quite dangerous and include pneumonia, bacteremia, sepsis, and meningitis. Life span is often very short without treatment; however, early discovery and treatment with gene therapy and bone marrow transplantation can be curative.
- Published on
Pathology - Allergic Rhinitis
This condition is characterized by a Type I (IgE-mediated) acute hypersensitivity reaction to environmental allergens. Patients will often have a personal or family history of other atopic diseases such as asthma or atopic dermatitis. The syndrome is marked by a predisposition to produce IgE antibodies to environmental antigens. As these antigens are filtered by the nasal airways, interaction with surface-bound IgE antibodies on mast cells and basophils triggers a release of preformed mediators and the de novo synthesis of additional mediators, as well as the creation and release of proinflammatory cytokines. Interaction of mediators induces a complicated reaction in target organs, which includes the release of histamine and other stored mediators in the initiation of a complex cascade of actions. Frequent or persistent exposure leads to mucus hypersecretion, IgE production, eosinophilia, and tissue damage. Patients will most usually appear with congestion, clear nasal discharge, pale or bluish nasal mucosa, and possibly infraorbital cyanosis. Nasal, ocular, and/or palate irritation can be present as well.
Extensive rubbing of the nose over an extended period of time can also lead to a characteristic transverse nasal crease.
A positive intracutaneous skin test can provide proof of triggering allergens.
This condition is characterized by a Type I (IgE-mediated) acute hypersensitivity reaction to environmental allergens. Patients will often have a personal or family history of other atopic diseases such as asthma or atopic dermatitis. The syndrome is marked by a predisposition to produce IgE antibodies to environmental antigens. As these antigens are filtered by the nasal airways, interaction with surface-bound IgE antibodies on mast cells and basophils triggers a release of preformed mediators and the de novo synthesis of additional mediators, as well as the creation and release of proinflammatory cytokines. Interaction of mediators induces a complicated reaction in target organs, which includes the release of histamine and other stored mediators in the initiation of a complex cascade of actions. Frequent or persistent exposure leads to mucus hypersecretion, IgE production, eosinophilia, and tissue damage. Patients will most usually appear with congestion, clear nasal discharge, pale or bluish nasal mucosa, and possibly infraorbital cyanosis. Nasal, ocular, and/or palate irritation can be present as well.
Extensive rubbing of the nose over an extended period of time can also lead to a characteristic transverse nasal crease.
A positive intracutaneous skin test can provide proof of triggering allergens.
- Published on
Pathology - Bruton's Agammaglobulinemia
Bruton’s agammaglobulinemia is an X-linked recessive illness caused by loss of a tyrosine kinase (Btk) gene, leading in the failure of pre-B cells to grow into mature B cells. All patients will be male and typically begin presenting with illnesses around about 6 months of age, when maternal antibody protection ends. Recurrent febrile sinopulmonary infections owing to pneumococcus and Haemophilus are prevalent. Patients may be noticed to have absent tonsils, as in this example, due to lack of lymphoproliferative germinal centers. Laboratory investigations will show absence of B cells on peripheral smear, and immunoglobulin electrophoresis will demonstrate a severely reduced immunoglobulin level, usually at 10% or less of the normal value.
Bruton’s agammaglobulinemia is an X-linked recessive illness caused by loss of a tyrosine kinase (Btk) gene, leading in the failure of pre-B cells to grow into mature B cells. All patients will be male and typically begin presenting with illnesses around about 6 months of age, when maternal antibody protection ends. Recurrent febrile sinopulmonary infections owing to pneumococcus and Haemophilus are prevalent. Patients may be noticed to have absent tonsils, as in this example, due to lack of lymphoproliferative germinal centers. Laboratory investigations will show absence of B cells on peripheral smear, and immunoglobulin electrophoresis will demonstrate a severely reduced immunoglobulin level, usually at 10% or less of the normal value.
- Published on
Pathology - IgA Deficiency
IgA deficiency is a frequent genetic condition causing varying hypogammaglobulinemia. Patients may acquire a hypogammaglobulinemia at any age and may be asymptomatic. The condition develops when the respective immunoglobulin-producing B cells fail to mature into plasma cells. Patients have normal B cell numbers, but measurably reduced amounts of one particular kind of immunoglobulin. This instance depicts the classic symptomatic patient. Deficiency in secretory IgA (immunoglobulin A) at very low levels results in recurrent sinopulmonary and, most notably, Giardia infections. This patient is considerably dehydrated on physical examination, which can occur following considerable fluid loss from giardiasis. It is also important to recognize that anaphylaxis can occur if an IgAdeficient patient is exposed to blood products that contain IgA, which may be the first recognition of previously asymptomatic IgA-deficient adult. In addition, patients have elevated rates of allergy and autoimmune illnesses.
A similar presentation in an adult patient with decreased levels of numerous immunoglobulins (as opposed to a single immunoglobulin deficiency in IgA deficiency) is mixed variable immunodeficiency, from a failure in B-cell maturation to plasma cells.
IgA deficiency is a frequent genetic condition causing varying hypogammaglobulinemia. Patients may acquire a hypogammaglobulinemia at any age and may be asymptomatic. The condition develops when the respective immunoglobulin-producing B cells fail to mature into plasma cells. Patients have normal B cell numbers, but measurably reduced amounts of one particular kind of immunoglobulin. This instance depicts the classic symptomatic patient. Deficiency in secretory IgA (immunoglobulin A) at very low levels results in recurrent sinopulmonary and, most notably, Giardia infections. This patient is considerably dehydrated on physical examination, which can occur following considerable fluid loss from giardiasis. It is also important to recognize that anaphylaxis can occur if an IgAdeficient patient is exposed to blood products that contain IgA, which may be the first recognition of previously asymptomatic IgA-deficient adult. In addition, patients have elevated rates of allergy and autoimmune illnesses.
A similar presentation in an adult patient with decreased levels of numerous immunoglobulins (as opposed to a single immunoglobulin deficiency in IgA deficiency) is mixed variable immunodeficiency, from a failure in B-cell maturation to plasma cells.
- Published on
Pathology - Urge Urinary Incontinence
This ailment, also known as “overactive bladder” is characterized by leakage of pee because of the inability to defer voiding after sensing sense of bladder fullness (urinary urgency). Most prevalent etiology is motor or sensory instability (bladder spasms or contractions) of the detrusor muscle of the urine bladder. This instability can be connected with local genitourinary problems (UTIs, tumors, outflow obstruction) or CNS disorders (stroke, Parkinsonism, spinal cord injury, or disease); however, in most cases, no explanation can be determined. Evaluation of this condition should include evaluation for UTI or other diseases as well as functional testing of the bladder (urodynamic testing). Treatment with behavioral therapies or anticholinergic medication to relax bladder musculature is generally highly helpful. The patient in the vignette is taking hydrochlorothiazide to manage her hypertension — this diuretic medicine may be unwittingly contributing to her symptoms.
This ailment, also known as “overactive bladder” is characterized by leakage of pee because of the inability to defer voiding after sensing sense of bladder fullness (urinary urgency). Most prevalent etiology is motor or sensory instability (bladder spasms or contractions) of the detrusor muscle of the urine bladder. This instability can be connected with local genitourinary problems (UTIs, tumors, outflow obstruction) or CNS disorders (stroke, Parkinsonism, spinal cord injury, or disease); however, in most cases, no explanation can be determined. Evaluation of this condition should include evaluation for UTI or other diseases as well as functional testing of the bladder (urodynamic testing). Treatment with behavioral therapies or anticholinergic medication to relax bladder musculature is generally highly helpful. The patient in the vignette is taking hydrochlorothiazide to manage her hypertension — this diuretic medicine may be unwittingly contributing to her symptoms.
- Published on
Pathology - Overflow Urinary Incontinence
This ailment happens due to involuntary loss of urine from an overly full bladder, which has some form of outlet obstruction. Common causes of this form of incontinence include BPH, prostate cancer, urethral narrowing/strictures, or neuromuscular diseases that impede bladder motility (spinal cord lesions, multiple sclerosis). In overflow incontinence, the bladder is always continually full so that it regularly leaks urine. Difficulty beginning urination and weakening of urine stream are typically noted as the inflated urinary bladder becomes functionally atonic or at least significantly less able to contract than normal bladder musculature. The condition may be worsened by usage of anticholinergic medicines or even NSAIDs, which may impede bladder motility further.
Presence of a considerable volume of pee in the bladder after voiding (either by ultrasound assessment or urinary catheterization) is indicative of this disorder. Lower abdominal distention is detected as the patient’s enlarged bladder moves from the pelvis into the lower abdomen.
This ailment happens due to involuntary loss of urine from an overly full bladder, which has some form of outlet obstruction. Common causes of this form of incontinence include BPH, prostate cancer, urethral narrowing/strictures, or neuromuscular diseases that impede bladder motility (spinal cord lesions, multiple sclerosis). In overflow incontinence, the bladder is always continually full so that it regularly leaks urine. Difficulty beginning urination and weakening of urine stream are typically noted as the inflated urinary bladder becomes functionally atonic or at least significantly less able to contract than normal bladder musculature. The condition may be worsened by usage of anticholinergic medicines or even NSAIDs, which may impede bladder motility further.
Presence of a considerable volume of pee in the bladder after voiding (either by ultrasound assessment or urinary catheterization) is indicative of this disorder. Lower abdominal distention is detected as the patient’s enlarged bladder moves from the pelvis into the lower abdomen.
- Published on
Pathology - Stress Urinary Incontinence
This involuntary leakage of pee happens as a result of loss of pelvic floor muscles or a weakening of the wall between the bladder and vagina. The average adult bladder can retain 350 to 550 mL of pee and is maintained by pelvic floor musculature. Primary pelvic musculature involved in this condition includes the urethral sphincter muscle and detrusor muscle of the bladder wall. Weakness often arises as one sequelae of pregnancy/childbirth and/or menopause loss of estrogen support to vaginal tissues. In stress incontinence, the urinary sphincter muscle is not able to prevent urine from flowing when pressure (e.g., coughing, laughing, sneezing) is exerted on the abdomen. Diagnosis of this ailment may entail ultrasound assessment of the bladder, cystoscopy, urinalysis, and bladder stress test.
This involuntary leakage of pee happens as a result of loss of pelvic floor muscles or a weakening of the wall between the bladder and vagina. The average adult bladder can retain 350 to 550 mL of pee and is maintained by pelvic floor musculature. Primary pelvic musculature involved in this condition includes the urethral sphincter muscle and detrusor muscle of the bladder wall. Weakness often arises as one sequelae of pregnancy/childbirth and/or menopause loss of estrogen support to vaginal tissues. In stress incontinence, the urinary sphincter muscle is not able to prevent urine from flowing when pressure (e.g., coughing, laughing, sneezing) is exerted on the abdomen. Diagnosis of this ailment may entail ultrasound assessment of the bladder, cystoscopy, urinalysis, and bladder stress test.
- Published on
Pathology - Functional Urinary Incontinence
This problem arises when a person senses the desire to urinate but cannot make it to the bathroom. The urine loss may be substantial. This disorder is widespread in elderly adults - for this reason, physiologic reasons of incontinence must be ruled out in order to achieve this diagnosis. The patient in the vignette has been evaluated for UTI and constipation, frequent causes of incontinence in this age group. His condition coincides with transferring to a facility where it is quite likely that he is not granted bathroom access as often as needed. Causes of functional incontinence include confusion; dementia; poor eyesight; poor mobility; poor dexterity; unwillingness to toilet because of melancholy, anxiety, or rage; alcoholism; or being in a setting in which it is hard to reach a toilet. Examples include someone in a wheelchair or with dementia. Patients with functional incontinence may have issues thinking, moving, or communicating that prevent them from reaching a toilet. The term “functional” denotes that the disease is not related to anatomic or physiologic dysfunction but rather to emotional or access/mobility concerns.
This problem arises when a person senses the desire to urinate but cannot make it to the bathroom. The urine loss may be substantial. This disorder is widespread in elderly adults - for this reason, physiologic reasons of incontinence must be ruled out in order to achieve this diagnosis. The patient in the vignette has been evaluated for UTI and constipation, frequent causes of incontinence in this age group. His condition coincides with transferring to a facility where it is quite likely that he is not granted bathroom access as often as needed. Causes of functional incontinence include confusion; dementia; poor eyesight; poor mobility; poor dexterity; unwillingness to toilet because of melancholy, anxiety, or rage; alcoholism; or being in a setting in which it is hard to reach a toilet. Examples include someone in a wheelchair or with dementia. Patients with functional incontinence may have issues thinking, moving, or communicating that prevent them from reaching a toilet. The term “functional” denotes that the disease is not related to anatomic or physiologic dysfunction but rather to emotional or access/mobility concerns.
