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Pathology - Subarachnoid Hemorrhage and Berry Aneurysm
Subarachnoid bleeding can be caused by the rupture of a berry aneurysm, trauma, or arteriovenous malformation.
Berry aneurysms typically happen randomly, however variables that increase the risk include hypertension, smoking, aortic coarctation, APKD, connective tissue disorders, and neurofibromatosis type I.
Berry aneurysms are more likely to rupture in women and individuals over the age of 40.
Subarachnoid hemorrhage is the presence of blood in the subarachnoid space. Fibrosis, which might occur after the blood is cleared, may cause obstruction of cerebrospinal fluid.
Berry aneurysm typically develops at the junctions of arteries in the circle of Willis. It involves a bulging of the artery wall due to thickening of the inner layer and thinning of the middle layer at the neck of the aneurysm, with the middle layer being absent in the sac wall.
Clinical presentation of subarachnoid hemorrhage includes severe headache, nausea, vomiting, loss of consciousness, possible fever, and nuchal stiffness. It can be life-threatening.
Laboratory results: Blood is found in the cerebrospinal fluid after a lumbar puncture.
Imaging: CT scan shows blood in basal cisterns.
Therapy
Treatment options include surgical repair, coil embolization, and supportive care, with the therapeutic method determined by cerebral angiography.
Arteriovenous malformations are vascular anomalies present from birth in the cerebrum, typically seen in the subarachnoid space but can also extend into brain tissue. The symptoms typically appear in young people as seizures or cerebral bleeding.
Subarachnoid bleeding can be caused by the rupture of a berry aneurysm, trauma, or arteriovenous malformation.
Berry aneurysms typically happen randomly, however variables that increase the risk include hypertension, smoking, aortic coarctation, APKD, connective tissue disorders, and neurofibromatosis type I.
Berry aneurysms are more likely to rupture in women and individuals over the age of 40.
Subarachnoid hemorrhage is the presence of blood in the subarachnoid space. Fibrosis, which might occur after the blood is cleared, may cause obstruction of cerebrospinal fluid.
Berry aneurysm typically develops at the junctions of arteries in the circle of Willis. It involves a bulging of the artery wall due to thickening of the inner layer and thinning of the middle layer at the neck of the aneurysm, with the middle layer being absent in the sac wall.
Clinical presentation of subarachnoid hemorrhage includes severe headache, nausea, vomiting, loss of consciousness, possible fever, and nuchal stiffness. It can be life-threatening.
Laboratory results: Blood is found in the cerebrospinal fluid after a lumbar puncture.
Imaging: CT scan shows blood in basal cisterns.
Therapy
Treatment options include surgical repair, coil embolization, and supportive care, with the therapeutic method determined by cerebral angiography.
Arteriovenous malformations are vascular anomalies present from birth in the cerebrum, typically seen in the subarachnoid space but can also extend into brain tissue. The symptoms typically appear in young people as seizures or cerebral bleeding.
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Pathology - Alzheimer Disease
The cause is uncertain, however hypotheses including aberrant amyloid gene expression leading to elevated Alpha beta protein, choline acetyltransferase deficiency causing reduced acetylcholine levels, or atrophy of the nucleus basalis of Meynert. Familial Alzheimer's disease is caused by mutations in the amyloid precursor protein (APP) gene on chromosome 21, mutations in presenilin genes on chromosomes 1 and 14, and the beta 4 allele of apolipoprotein E on chromosome 19.
Impacts half of those over the age of 85.
Gross Pathology : Brain cortical atrophy with expansion of sulci and ventricles.
Microscopic pathology features include neurofibrillary tangles made of tau protein displacing the nucleus in the cytoplasm, neuritic plaques with an alpha beta protein core surrounded by astrocytes, amyloid angiopathy, Hirano bodies in hippocampal cells, and granulovacuolar degeneration with cytoplasmic vacuoles in hippocampal cells.
Clinical Symptoms and Signs
Dementia manifests as a steady decline in memory, disorientation, language difficulties, visuospatial impairments, loss of motor function, or incontinence.
Administer Donepezil, an acetylcholinesterase inhibitor, or memantine, an NMDA receptor antagonist, to slow down disease progression.
Chronic illness with no remedy.
The cause is uncertain, however hypotheses including aberrant amyloid gene expression leading to elevated Alpha beta protein, choline acetyltransferase deficiency causing reduced acetylcholine levels, or atrophy of the nucleus basalis of Meynert. Familial Alzheimer's disease is caused by mutations in the amyloid precursor protein (APP) gene on chromosome 21, mutations in presenilin genes on chromosomes 1 and 14, and the beta 4 allele of apolipoprotein E on chromosome 19.
Impacts half of those over the age of 85.
Gross Pathology : Brain cortical atrophy with expansion of sulci and ventricles.
Microscopic pathology features include neurofibrillary tangles made of tau protein displacing the nucleus in the cytoplasm, neuritic plaques with an alpha beta protein core surrounded by astrocytes, amyloid angiopathy, Hirano bodies in hippocampal cells, and granulovacuolar degeneration with cytoplasmic vacuoles in hippocampal cells.
Clinical Symptoms and Signs
Dementia manifests as a steady decline in memory, disorientation, language difficulties, visuospatial impairments, loss of motor function, or incontinence.
Administer Donepezil, an acetylcholinesterase inhibitor, or memantine, an NMDA receptor antagonist, to slow down disease progression.
Chronic illness with no remedy.
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Pathology - Pick Disease
The cause is unidentified, but there is evidence suggesting that mutations on chromosomes 3, 9, and 17 are inherited in an autosomal dominant manner in up to 50% of cases.
Pathology: Uneven shrinkage of the frontal and temporal lobes of the brain.
Microscopic examination reveals the presence of Pick cells, which are enlarged neurons, or Pick bodies, which are spherical, silver-staining, neurofilamentous entities present in the cytoplasm within neurons.
Symptoms and signs
Dementia manifests with predominant personality changes, atypical behavioral patterns, and speech problems.
Therapies
Address symptoms; handle behavioral issues.
Chronic illness with no remedy.
Dementia with Lewy bodies is a progressive form of dementia characterized by parkinsonism and hallucinations. Histologically, it is identified by the presence of Lewy bodies, which are eosinophilic inclusion bodies found in the cytoplasm of substantia nigra cells.
The cause is unidentified, but there is evidence suggesting that mutations on chromosomes 3, 9, and 17 are inherited in an autosomal dominant manner in up to 50% of cases.
Pathology: Uneven shrinkage of the frontal and temporal lobes of the brain.
Microscopic examination reveals the presence of Pick cells, which are enlarged neurons, or Pick bodies, which are spherical, silver-staining, neurofilamentous entities present in the cytoplasm within neurons.
Symptoms and signs
Dementia manifests with predominant personality changes, atypical behavioral patterns, and speech problems.
Therapies
Address symptoms; handle behavioral issues.
Chronic illness with no remedy.
Dementia with Lewy bodies is a progressive form of dementia characterized by parkinsonism and hallucinations. Histologically, it is identified by the presence of Lewy bodies, which are eosinophilic inclusion bodies found in the cytoplasm of substantia nigra cells.
Pick Disease / Frontotemporal Dementia
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Pathology - Huntington Disease
Huntington's disease is an autosomal dominant disorder caused by an excessive number of CAG repeats in the Huntington disease gene located on chromosome 4.
Typically appears between the ages of 30 and 50.
Study of diseases
Findings: Degeneration of caudate nucleus and putamen, possible atrophy of globus pallidus and frontal lobe, and enlargement of lateral and third ventricles.
Microscopic findings include the loss of GABAergic neurons in the striatum and the presence of fibrillary gliosis.
Clinical Symptoms
A progressive disorder characterized by chorea (involuntary jerky movements), cognitive decline, and mood disorders.
Ultimately advances to profound dementia.
Treatment aimed at alleviating symptoms of dyskinesia and mood disorders.
Typically results in death after 15-20 years of being diagnosed.
Huntington disease, fragile X syndrome, and myotonic dystrophy exhibit anticipation, where the number of repeats grows in each generation, leading to progressively severe disease symptoms.
Huntington's disease is an autosomal dominant disorder caused by an excessive number of CAG repeats in the Huntington disease gene located on chromosome 4.
Typically appears between the ages of 30 and 50.
Study of diseases
Findings: Degeneration of caudate nucleus and putamen, possible atrophy of globus pallidus and frontal lobe, and enlargement of lateral and third ventricles.
Microscopic findings include the loss of GABAergic neurons in the striatum and the presence of fibrillary gliosis.
Clinical Symptoms
A progressive disorder characterized by chorea (involuntary jerky movements), cognitive decline, and mood disorders.
Ultimately advances to profound dementia.
Treatment aimed at alleviating symptoms of dyskinesia and mood disorders.
Typically results in death after 15-20 years of being diagnosed.
Huntington disease, fragile X syndrome, and myotonic dystrophy exhibit anticipation, where the number of repeats grows in each generation, leading to progressively severe disease symptoms.
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Pathology - Parkinson Disease
Cause unclear.
Typically occurs in those over the age of 50.
Pathology: The substantia nigra and locus ceruleus seem pale upon examination.
Microscopic examination reveals the absence of pigmented dopaminergic neurons in the substantia nigra along with gliosis. Additionally, Lewy bodies, which are eosinophilic intracytoplasmic inclusion bodies, are present in the neurons of the substantia nigra.
Pathophysiology: Decreased dopaminergic input to the striatum causes reduced activation of the basal ganglia motor circuit, resulting in bradykinesia.
Clinical Symptoms
Cluster of symptoms including pill-rolling tremor, bradykinesia, shuffling gait, rigidity with cogwheeling of extremities upon passive motion, postural instability, and expressionless facies, collectively referred to as parkinsonism.
10%-15% of individuals with Parkinson's disease experience dementia.
Treatment involves pharmacologic therapy using medications such as amantadine, anticholinergics, levodopa, dopamine agonists, and MAO-B inhibitors.
Additional factors leading to parkinsonism are recurrent head injuries (common in boxers), some medications (such as MPTP), parkinsonism following encephalitis (seen after the influenza outbreak in the early 1900s), and Shy-Drager syndrome (parkinsonism accompanied by orthostatic hypotension and autonomic dysfunction).
Cause unclear.
Typically occurs in those over the age of 50.
Pathology: The substantia nigra and locus ceruleus seem pale upon examination.
Microscopic examination reveals the absence of pigmented dopaminergic neurons in the substantia nigra along with gliosis. Additionally, Lewy bodies, which are eosinophilic intracytoplasmic inclusion bodies, are present in the neurons of the substantia nigra.
Pathophysiology: Decreased dopaminergic input to the striatum causes reduced activation of the basal ganglia motor circuit, resulting in bradykinesia.
Clinical Symptoms
Cluster of symptoms including pill-rolling tremor, bradykinesia, shuffling gait, rigidity with cogwheeling of extremities upon passive motion, postural instability, and expressionless facies, collectively referred to as parkinsonism.
10%-15% of individuals with Parkinson's disease experience dementia.
Treatment involves pharmacologic therapy using medications such as amantadine, anticholinergics, levodopa, dopamine agonists, and MAO-B inhibitors.
Additional factors leading to parkinsonism are recurrent head injuries (common in boxers), some medications (such as MPTP), parkinsonism following encephalitis (seen after the influenza outbreak in the early 1900s), and Shy-Drager syndrome (parkinsonism accompanied by orthostatic hypotension and autonomic dysfunction).
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Pathology - Amyotrophic Lateral Sclerosis
The cause of sporadic amyotrophic lateral sclerosis (ALS) is unknown. 5%-10% of cases are familial and are inherited by autosomal dominant inheritance of a mutation on chromosome 21 or a deficiency in the SOD-1 gene, which is involved in scavenging free radicals.
Primarily impacts males over the age of 40.
Progressive illness linked to the deterioration of both upper and lower motor neurons.
Spinal cord: Decreased anterior horn neurons with reactive gliosis; degeneration of corticospinal tract neurons.
Neurogenic atrophy of muscle with target fibers (fibers showing a dark center area on cross-section).
Lower motor neuron indications include muscular atrophy and fasciculations.
Upper motor neuron indications include hyperreflexia, positive Babinski sign, and spasticity.
Motor neuron degeneration typically manifests with first symptoms of hand weakness, cramping, and spasticity in the arms and legs. Engagement of respiratory muscles results in lung infections and ultimately mortality.
Therapy
Supportive Measures
Respiratory failure typically leads to death within 5 years of being diagnosed.
Werdnig-Hoffmann syndrome is an autosomal recessive disorder that impacts the lower motor neurons and is linked to the degradation of anterior horns. It manifests in infancy with tongue fasciculations and symptoms of a weak or floppy newborn.
The cause of sporadic amyotrophic lateral sclerosis (ALS) is unknown. 5%-10% of cases are familial and are inherited by autosomal dominant inheritance of a mutation on chromosome 21 or a deficiency in the SOD-1 gene, which is involved in scavenging free radicals.
Primarily impacts males over the age of 40.
Progressive illness linked to the deterioration of both upper and lower motor neurons.
Spinal cord: Decreased anterior horn neurons with reactive gliosis; degeneration of corticospinal tract neurons.
Neurogenic atrophy of muscle with target fibers (fibers showing a dark center area on cross-section).
Lower motor neuron indications include muscular atrophy and fasciculations.
Upper motor neuron indications include hyperreflexia, positive Babinski sign, and spasticity.
Motor neuron degeneration typically manifests with first symptoms of hand weakness, cramping, and spasticity in the arms and legs. Engagement of respiratory muscles results in lung infections and ultimately mortality.
Therapy
Supportive Measures
Respiratory failure typically leads to death within 5 years of being diagnosed.
Werdnig-Hoffmann syndrome is an autosomal recessive disorder that impacts the lower motor neurons and is linked to the degradation of anterior horns. It manifests in infancy with tongue fasciculations and symptoms of a weak or floppy newborn.
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Pathology - Prostate Carcinoma
Risk factors include a family history of prostate cancer or being of African American descent.
Prevalent in males over the age of 50; the most frequent cancer in men and the second most prevalent cause of cancer-related deaths in men.
Gross: Irregular nodules originating from glands in the periphery zone of the posterior lobe.
Microscopic examination reveals adenocarcinoma characterized by well-defined glands lined by cuboidal cells with big nuclei and conspicuous nucleoli. It may also present as undifferentiated with cells developing in cords or sheets, often showing invasion of vascular or lymphatic arteries of the prostatic capsule.
In advanced stages, it can develop into bone osteoblastic metastasis by the spread of cancer cells in the bloodstream.
Often without symptoms, but can cause dysuria, increased urine frequency, or back pain (if cancer has spread to bone); typically identified during a digital rectal examination by detecting an irregular, enlarged, firm lump, and confirmed with a prostatic biopsy.
Lab results show elevated serum levels of PSA and prostatic acid phosphatase, which are useful indicators of tumor growth. There is also an increase in total PSA with a decrease in the free PSA fraction, as well as elevated serum alkaline phosphatase, indicating possible osteoblastic metastasis.
Treatments include prostatectomy, radiation, GnRH analogues (leuprolide), antiandrogens (e.g., flutamide), and chemotherapy.
The Gleason system of grading predicts whether prostate cancer will progress slowly or rapidly depending on the tumor's differentiation.
Annual PSA tests and digital rectal examination should be provided for screening starting at age 50.
Risk factors include a family history of prostate cancer or being of African American descent.
Prevalent in males over the age of 50; the most frequent cancer in men and the second most prevalent cause of cancer-related deaths in men.
Gross: Irregular nodules originating from glands in the periphery zone of the posterior lobe.
Microscopic examination reveals adenocarcinoma characterized by well-defined glands lined by cuboidal cells with big nuclei and conspicuous nucleoli. It may also present as undifferentiated with cells developing in cords or sheets, often showing invasion of vascular or lymphatic arteries of the prostatic capsule.
In advanced stages, it can develop into bone osteoblastic metastasis by the spread of cancer cells in the bloodstream.
Often without symptoms, but can cause dysuria, increased urine frequency, or back pain (if cancer has spread to bone); typically identified during a digital rectal examination by detecting an irregular, enlarged, firm lump, and confirmed with a prostatic biopsy.
Lab results show elevated serum levels of PSA and prostatic acid phosphatase, which are useful indicators of tumor growth. There is also an increase in total PSA with a decrease in the free PSA fraction, as well as elevated serum alkaline phosphatase, indicating possible osteoblastic metastasis.
Treatments include prostatectomy, radiation, GnRH analogues (leuprolide), antiandrogens (e.g., flutamide), and chemotherapy.
The Gleason system of grading predicts whether prostate cancer will progress slowly or rapidly depending on the tumor's differentiation.
Annual PSA tests and digital rectal examination should be provided for screening starting at age 50.
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Pathology - Penile Diseases
Conditions known as Hypospadias and Epispadias
Definition: Congenital anomaly causing the urethral opening to be located abnormally on the underside (hypospadias) or top side (epispadias) of the penis; often linked with undescended testicles and abnormalities in the urinary system (bladder exstrophy).
Clinical symptoms: Obstruction of the urinary tract and abnormal ejaculation.
Phimosis is the condition when the foreskin is abnormally tight and cannot be pulled back over the head of the penis. It is typically caused by a congenital issue or can occur from inflammation or injury.
Clinical symptoms: Manifests as pain in the penis or sudden inability to urinate.
Peyronie's disease is characterized by the development of fibrous scar tissue on the dorsum of the penis, with the cause being unknown.
Clinical symptoms: Abnormal bending of the penis or narrowing of the urethra that happens in elderly males.
Balanitis is the inflammation of the glans penis, typically caused by various infections such as syphilis, gonorrhea, herpes, chancroid, Candida, and Gardnerella.
Clinical symptoms: Penile infections are more common in uncircumcised men who have inadequate hygiene.
Conditions known as Hypospadias and Epispadias
Definition: Congenital anomaly causing the urethral opening to be located abnormally on the underside (hypospadias) or top side (epispadias) of the penis; often linked with undescended testicles and abnormalities in the urinary system (bladder exstrophy).
Clinical symptoms: Obstruction of the urinary tract and abnormal ejaculation.
Phimosis is the condition when the foreskin is abnormally tight and cannot be pulled back over the head of the penis. It is typically caused by a congenital issue or can occur from inflammation or injury.
Clinical symptoms: Manifests as pain in the penis or sudden inability to urinate.
Peyronie's disease is characterized by the development of fibrous scar tissue on the dorsum of the penis, with the cause being unknown.
Clinical symptoms: Abnormal bending of the penis or narrowing of the urethra that happens in elderly males.
Balanitis is the inflammation of the glans penis, typically caused by various infections such as syphilis, gonorrhea, herpes, chancroid, Candida, and Gardnerella.
Clinical symptoms: Penile infections are more common in uncircumcised men who have inadequate hygiene.
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Pathology - Penile Cancer
Bowen's disease impacts men over the age of 50 who are not circumcised.
Erythroplasia of Queyrat typically occurs in individuals in their fifth decade and is considered a form of Bowen's disease.
Bowenoid papulosis primarily affects a younger demographic.
Penile Squamous Cell Carcinoma has a higher occurrence in Asia and Africa, typically affecting those aged 40-70. Risk factors include being uncircumcised, having poor hygiene, and being infected with HPV types 16, 18, 31, and 33.
Bowen's disease is characterized by the abnormal growth of epidermal cells with atypical cell divisions, although the basement membrane between the epidermis and dermis remains intact.
Erythroplasia of Queyrat and Bowenoid Papulosis are histologically similar to Bowen Disease.
Penile Squamous Cell Carcinoma originates from Bowen Disease and Erythroplasia of Queyrat. Papillary lesions resemble condyloma acuminata and form a cauliflower-like mass. Flat lesions present as thickened regions of epithelium with mucosal fissuring.
Bowen's disease presents as a single red patch on the penis or scrotum; less than 10% progress to invasive cancer and is linked to a higher chance of developing internal malignancies.
Erythroplasia of Queyrat presents as a solitary red patch on the glans penis or prepuce, with a 10% chance of progressing to aggressive cancer.
Bowenoid Papulosis is characterized by many wart-like lesions similar to condylomata acuminatum, although it does not develop into aggressive cancer.
Penile Squamous Cell Carcinoma is a painless lesion that can bleed, develop secondary ulceration, and become infected.
Excision of penile squamous cell cancer.
Bowen's disease impacts men over the age of 50 who are not circumcised.
Erythroplasia of Queyrat typically occurs in individuals in their fifth decade and is considered a form of Bowen's disease.
Bowenoid papulosis primarily affects a younger demographic.
Penile Squamous Cell Carcinoma has a higher occurrence in Asia and Africa, typically affecting those aged 40-70. Risk factors include being uncircumcised, having poor hygiene, and being infected with HPV types 16, 18, 31, and 33.
Bowen's disease is characterized by the abnormal growth of epidermal cells with atypical cell divisions, although the basement membrane between the epidermis and dermis remains intact.
Erythroplasia of Queyrat and Bowenoid Papulosis are histologically similar to Bowen Disease.
Penile Squamous Cell Carcinoma originates from Bowen Disease and Erythroplasia of Queyrat. Papillary lesions resemble condyloma acuminata and form a cauliflower-like mass. Flat lesions present as thickened regions of epithelium with mucosal fissuring.
Bowen's disease presents as a single red patch on the penis or scrotum; less than 10% progress to invasive cancer and is linked to a higher chance of developing internal malignancies.
Erythroplasia of Queyrat presents as a solitary red patch on the glans penis or prepuce, with a 10% chance of progressing to aggressive cancer.
Bowenoid Papulosis is characterized by many wart-like lesions similar to condylomata acuminatum, although it does not develop into aggressive cancer.
Penile Squamous Cell Carcinoma is a painless lesion that can bleed, develop secondary ulceration, and become infected.
Excision of penile squamous cell cancer.
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Pathology - Congenital CNS Abnormalities
Neural Tube Defects
Cause: Linked to low levels of folate during early pregnancy and high levels of alpha-fetoprotein.
Spina bifida is a condition where the posterior end of the neural tube fails to close properly, leading to a bony defect in the vertebrae. This defect can cause the meninges to herniate (meningocele) or both the meninges and spinal cord to herniate (meningomyelocele), resulting in neurological symptoms. In some cases, the bony defect may not cause any symptoms other than changes in the skin over the affected area, known as spina bifida occulta.
Encephalocele is a condition where a defect in the cranium causes the brain to protrude through the skull.
Anencephaly is the incomplete closure of the anterior end of the neural tube, leading to the lack of the fetal brain and sometimes the skull covering it.
Neural Tube Defects
Cause: Linked to low levels of folate during early pregnancy and high levels of alpha-fetoprotein.
Spina bifida is a condition where the posterior end of the neural tube fails to close properly, leading to a bony defect in the vertebrae. This defect can cause the meninges to herniate (meningocele) or both the meninges and spinal cord to herniate (meningomyelocele), resulting in neurological symptoms. In some cases, the bony defect may not cause any symptoms other than changes in the skin over the affected area, known as spina bifida occulta.
Encephalocele is a condition where a defect in the cranium causes the brain to protrude through the skull.
Anencephaly is the incomplete closure of the anterior end of the neural tube, leading to the lack of the fetal brain and sometimes the skull covering it.
Spina Bifida
Holoprosencephaly is a condition where the forebrain of the embryo fails to split into bilateral cerebral hemispheres, resulting in insufficient separation of the cerebral hemispheres.
Clinical symptoms: Facial and neurological abnormalities.
Clinical symptoms: Facial and neurological abnormalities.
Holoprosencephaly
Arnold-Chiari Malformation is a condition where the cerebellum and medulla are displaced via the foramen magnum due to a tiny posterior fossa.
Symptoms and signs: Hydrocephalus is closely linked to thoracolumbar meningomyelocele and syringomyelia.
Symptoms and signs: Hydrocephalus is closely linked to thoracolumbar meningomyelocele and syringomyelia.
Arnold-Chiari Malformation is a condition where the cerebellum and medulla are displaced via the foramen magnum due to a tiny posterior fossa.
Symptoms and signs: Hydrocephalus is closely linked to thoracolumbar meningomyelocele and syringomyelia.
Symptoms and signs: Hydrocephalus is closely linked to thoracolumbar meningomyelocele and syringomyelia.
Dandy-Walker Malformation is a condition where there is a big space in the back of the brain with the cerebellar vermis replaced by a massive cyst. It is also linked to abnormalities in the brainstem nuclei.
Symptoms: Seizures and malfunctioning of the cerebellum.
