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Pathology - HELLP Syndrome
HELLP syndrome is a severe type of preeclampsia/eclampsia characterized by Hemolysis, Elevated Liver enzymes, and Low Platelet count. The pathogenesis is likely to entail inadequate invasion of maternal uterine arteries by the early trophoblast during implantation. Later in pregnancy this leads to oxidative stress in the placenta, which produces inflammatory chemicals that cause extensive endothelial injury in the mother. Platelet aggregation occurs at locations of endothelial damage, resulting in platelet depletion. Activation of platelets induces release of thromboxane A2 leading to vasospasm that is inadequately countered by endothelial relaxant factors and prostacyclin due to loss of endothelium. Deposition of fibrin also occurs in the lumens of tiny arteries, which increases shearing forces on red cells and promotes hemolysis (notice elevated LDH levels).
Obstruction of hepatic sinusoids with fibrinlike deposits accounts for local necrosis and hepatocellular damage (notice increased liver enzymes). Vascular obstruction within the liver creates a buildup of pressure and in this instance subcapsular hematoma is observed on ultrasonography; this process may even terminate in liver rupture. Treatment may include glucocorticoids to advance fetal lung maturation, although timely delivery of the fetus is necessary. Unlike preeclampsia syndrome, delivery may not result in immediate resolution of maternal symptoms after the HELLP syndrome has established.
HELLP syndrome is a severe type of preeclampsia/eclampsia characterized by Hemolysis, Elevated Liver enzymes, and Low Platelet count. The pathogenesis is likely to entail inadequate invasion of maternal uterine arteries by the early trophoblast during implantation. Later in pregnancy this leads to oxidative stress in the placenta, which produces inflammatory chemicals that cause extensive endothelial injury in the mother. Platelet aggregation occurs at locations of endothelial damage, resulting in platelet depletion. Activation of platelets induces release of thromboxane A2 leading to vasospasm that is inadequately countered by endothelial relaxant factors and prostacyclin due to loss of endothelium. Deposition of fibrin also occurs in the lumens of tiny arteries, which increases shearing forces on red cells and promotes hemolysis (notice elevated LDH levels).
Obstruction of hepatic sinusoids with fibrinlike deposits accounts for local necrosis and hepatocellular damage (notice increased liver enzymes). Vascular obstruction within the liver creates a buildup of pressure and in this instance subcapsular hematoma is observed on ultrasonography; this process may even terminate in liver rupture. Treatment may include glucocorticoids to advance fetal lung maturation, although timely delivery of the fetus is necessary. Unlike preeclampsia syndrome, delivery may not result in immediate resolution of maternal symptoms after the HELLP syndrome has established.
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Pathology - Hirsutism
Hirsutism refers to excessive hair development in regions of the body where terminal hair does not ordinarily occur or is limited. It is most typically seen in women in whom aberrant hair growth takes on a pattern of masculine hair growth. This issue is a medical symptom rather than an illness and should be investigated appropriately. Hirsutism can be induced by either an increase level of androgens or an oversensitivity of hair follicles to androgens. Symptoms of aberrant hair growth may be accompanied by additional indicators of enhanced androgenic circulation, such as deepening of the voice, increased muscular mass, or cystic acne. Increased circulating levels of insulin in women may contribute to hirsutism, as high insulin levels stimulate ovarian theca cells to produce androgens. In addition, excessive doses of insulin may act at IGF-1 receptors in these same cells, resulting in increased androgen synthesis. Evaluation of this disorder comprises serum FSH level, free cortisol, 21-alpha hydroxylase deficiency, human growth hormone, fasting blood sugar, and hemoglobin A1c to check for PCOS, adrenocorticosteroid excess, congenital adrenal hyperplasia, acromegaly, and insulin resistance, respectively. Imaging of ovaries and adrenal glands may be indicated in some instances. Careful examination of drugs is also necessary, as hirsutism can be seen as a side effect of various medications including phenytoin, aldomet, metoclopramide, danazol, oral contraceptives, or phenothiazines.
Hirsutism refers to excessive hair development in regions of the body where terminal hair does not ordinarily occur or is limited. It is most typically seen in women in whom aberrant hair growth takes on a pattern of masculine hair growth. This issue is a medical symptom rather than an illness and should be investigated appropriately. Hirsutism can be induced by either an increase level of androgens or an oversensitivity of hair follicles to androgens. Symptoms of aberrant hair growth may be accompanied by additional indicators of enhanced androgenic circulation, such as deepening of the voice, increased muscular mass, or cystic acne. Increased circulating levels of insulin in women may contribute to hirsutism, as high insulin levels stimulate ovarian theca cells to produce androgens. In addition, excessive doses of insulin may act at IGF-1 receptors in these same cells, resulting in increased androgen synthesis. Evaluation of this disorder comprises serum FSH level, free cortisol, 21-alpha hydroxylase deficiency, human growth hormone, fasting blood sugar, and hemoglobin A1c to check for PCOS, adrenocorticosteroid excess, congenital adrenal hyperplasia, acromegaly, and insulin resistance, respectively. Imaging of ovaries and adrenal glands may be indicated in some instances. Careful examination of drugs is also necessary, as hirsutism can be seen as a side effect of various medications including phenytoin, aldomet, metoclopramide, danazol, oral contraceptives, or phenothiazines.
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Pathology - Nephrolithiasis
This condition most usually manifests as in the vignette, with patients complaining of relatively quick onset of acute flank discomfort spreading to the front of the abdomen on the affected side. While there are some established risk factors for development of renal calculi such as usage of certain medications (hydrochlorothiazide), certain medical disorders (gout, hypercalcemia), or excessive dietary consumption of oxalate (tea, spinach, others), most of the time the etiology is unclear. Evaluation of stone type (struvite vs. calcium oxalate vs. other) can help to identify likely causation in some cases. Stones form in the kidney and migrate down the ureters and eventually expelled in the urine or eliminated using ultrasonic lithotripsy if too large to pass through the ureter. Clinical findings include hematuria, which may be gross or microscopic and systemic signs of illness (fever, nausea, chills), which may occur as a result of acute urinary blockage. Males are afflicted more regularly; repeated episodes are prevalent and can progress to tubular scarring and ultimately renal parenchymal involvement and irreversible kidney disease.
This condition most usually manifests as in the vignette, with patients complaining of relatively quick onset of acute flank discomfort spreading to the front of the abdomen on the affected side. While there are some established risk factors for development of renal calculi such as usage of certain medications (hydrochlorothiazide), certain medical disorders (gout, hypercalcemia), or excessive dietary consumption of oxalate (tea, spinach, others), most of the time the etiology is unclear. Evaluation of stone type (struvite vs. calcium oxalate vs. other) can help to identify likely causation in some cases. Stones form in the kidney and migrate down the ureters and eventually expelled in the urine or eliminated using ultrasonic lithotripsy if too large to pass through the ureter. Clinical findings include hematuria, which may be gross or microscopic and systemic signs of illness (fever, nausea, chills), which may occur as a result of acute urinary blockage. Males are afflicted more regularly; repeated episodes are prevalent and can progress to tubular scarring and ultimately renal parenchymal involvement and irreversible kidney disease.
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Pathology - Urinary Tract Infection
Pyelonephritis is a result of ascending infection from the lower urinary tract. Bacteria enter the urinary tract at the urethra and rise to the bladder, ureters, and kidneys. There are some mechanisms to restrict bacterial development, including acidic urine pH. However, females are more prone to developing UTIs due to the shorter urethral length and proximity of the urethral meatus to the vaginal introitus and anus.
Once the infection reaches the kidneys, it can spread hematogenously and produce signs of sepsis and eventually septic shock if left untreated. Therefore, patients should be hospitalized and treated with empiric intravenous antibiotics until the microorganism sensitivities are identified from the urine culture. The presence of nitrites in the urine suggests the presence of nitrate-reducing bacteria, whereas the presence of leukocyte esterase shows white blood cells in the urine. It is crucial to highlight that patients can have a UTI without the presence of nitrites in the urine if the infection is secondary to a bacterium that does not decrease nitrates.
Pyelonephritis is a result of ascending infection from the lower urinary tract. Bacteria enter the urinary tract at the urethra and rise to the bladder, ureters, and kidneys. There are some mechanisms to restrict bacterial development, including acidic urine pH. However, females are more prone to developing UTIs due to the shorter urethral length and proximity of the urethral meatus to the vaginal introitus and anus.
Once the infection reaches the kidneys, it can spread hematogenously and produce signs of sepsis and eventually septic shock if left untreated. Therefore, patients should be hospitalized and treated with empiric intravenous antibiotics until the microorganism sensitivities are identified from the urine culture. The presence of nitrites in the urine suggests the presence of nitrate-reducing bacteria, whereas the presence of leukocyte esterase shows white blood cells in the urine. It is crucial to highlight that patients can have a UTI without the presence of nitrites in the urine if the infection is secondary to a bacterium that does not decrease nitrates.
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Pathology - Dysfunctional Uterine Bleeding
Dysfunctional uterine bleeding ( DUB) is identified clinically following meticulous history and physical examination and appropriate laboratory test. DUB is caused by hormonal abnormalities in the hypothalamic–pituitary axis in the absence of obvious anatomical or biological disease. Most typically, DUB is related with anovulatory conditions occurring at the extremes of reproductive age, such as early puberty and perimenopause. In certain cases, women do not correctly develop and release a mature egg. Without appropriate ovulation, a corpus luteum does not form and progesterone levels are lowered, producing practically constant estrogen production and subsequent thickening of the uterine lining. Menstruation is sometimes delayed; when it occurs, it can be heavy and lengthy. This condition has been connected with psychological stress, fast weight gain or loss, other endocrinopathies, neoplasms, and medication use. Mechanisms of DUB are generally unknown and often, no specific cause is recognized. Laboratory assessment includes blood hemoglobin level; LH, FSH, prolactin, and TSH levels; evaluation for pregnancy; and androgen profile, if clinically needed. Evaluation of endometrial thickness using pelvic ultrasonography may be indicated in some cases. Symptoms of weariness mentioned in the patient in the vignette above may be attributed to anemia/low hemoglobin from repeated excessive blood loss during protracted menses. The term used to describe severe menstrual bleeding is menorrhagia. Metrorrhagia is used to characterize frequent (more often than every 28 days) bleeding or bleeding in between menstrual cycles.
Dysfunctional uterine bleeding ( DUB) is identified clinically following meticulous history and physical examination and appropriate laboratory test. DUB is caused by hormonal abnormalities in the hypothalamic–pituitary axis in the absence of obvious anatomical or biological disease. Most typically, DUB is related with anovulatory conditions occurring at the extremes of reproductive age, such as early puberty and perimenopause. In certain cases, women do not correctly develop and release a mature egg. Without appropriate ovulation, a corpus luteum does not form and progesterone levels are lowered, producing practically constant estrogen production and subsequent thickening of the uterine lining. Menstruation is sometimes delayed; when it occurs, it can be heavy and lengthy. This condition has been connected with psychological stress, fast weight gain or loss, other endocrinopathies, neoplasms, and medication use. Mechanisms of DUB are generally unknown and often, no specific cause is recognized. Laboratory assessment includes blood hemoglobin level; LH, FSH, prolactin, and TSH levels; evaluation for pregnancy; and androgen profile, if clinically needed. Evaluation of endometrial thickness using pelvic ultrasonography may be indicated in some cases. Symptoms of weariness mentioned in the patient in the vignette above may be attributed to anemia/low hemoglobin from repeated excessive blood loss during protracted menses. The term used to describe severe menstrual bleeding is menorrhagia. Metrorrhagia is used to characterize frequent (more often than every 28 days) bleeding or bleeding in between menstrual cycles.
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Pathology - Menopause
This symptoms occurs in women, most commonly in late fifth or early sixth decade of life. The diagnosis is most typically made clinically when a women of this age range ceases to have menstrual cycles for a straight 12-month time frame. Menopause is the outcome of a natural decline in ovarian production of estrogen and progesterone, clinically noticeable as a woman begins to experience more erratic and unpredictable menstrual cycles and ceases releasing viable eggs each month. While this decline in hormone production occurs across years (perimenopausal era), eventually menses will halt for 12 months or more at which time menopause is stated to have happened. Menopause that happens before the age of 40 and owing to extrinsic causes such as hysterectomy or chemotherapy is termed to be premature. Decreased hormone production in menopause is responsible for the common symptoms experienced by most women, including hot flashes (thought to be due to hypothalamic dysregulation), vaginal dryness and dyspareunia (due to atrophic changes in tissues supported by estrogen), and sleep abnormalities (thought to be due to loss of estrogenic effects on nervous tissue responsible for sleep/wake regulation).
Laboratory assessment of this disorder is usually not essential. If examined, blood FSH level will be significantly elevated as a result of pituitary reaction to low circulating estrogen levels.
This symptoms occurs in women, most commonly in late fifth or early sixth decade of life. The diagnosis is most typically made clinically when a women of this age range ceases to have menstrual cycles for a straight 12-month time frame. Menopause is the outcome of a natural decline in ovarian production of estrogen and progesterone, clinically noticeable as a woman begins to experience more erratic and unpredictable menstrual cycles and ceases releasing viable eggs each month. While this decline in hormone production occurs across years (perimenopausal era), eventually menses will halt for 12 months or more at which time menopause is stated to have happened. Menopause that happens before the age of 40 and owing to extrinsic causes such as hysterectomy or chemotherapy is termed to be premature. Decreased hormone production in menopause is responsible for the common symptoms experienced by most women, including hot flashes (thought to be due to hypothalamic dysregulation), vaginal dryness and dyspareunia (due to atrophic changes in tissues supported by estrogen), and sleep abnormalities (thought to be due to loss of estrogenic effects on nervous tissue responsible for sleep/wake regulation).
Laboratory assessment of this disorder is usually not essential. If examined, blood FSH level will be significantly elevated as a result of pituitary reaction to low circulating estrogen levels.
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Pathology -Primary Amenorrhea
This patient has primary amenorrhea — no beginning of menses in a female older than 16 years. This disorder may occur with or without other indicators of puberty and most usually happens as a result of anatomic, hormonal, or genetic abnormality. Anatomic causes include congenital lack of the uterus or vagina, presence of vaginal septum or imperforate hymen, blocked/narrowed cervix, or Müllerian agenesis. Hormonal reasons include pituitary (LH, FSH), ovarian malfunction, or androgen insensitivity. Genetic abnormalities include Turner’s syndrome (45 XO). If secondary sex traits are not present, gonadotropins (FSH, LH) are tested first. If levels are low, hypogonadotropic hypogonadism is present. If FSH and LH are excessive (hypergonadotropic hypogonadism), unresponsiveness of tissues (premature ovarian failure or Turner’s syndrome) is suspected. If secondary sex traits are present (as in the patient in the vignette), ultrasonography assessment of pelvic organs is indicated. If appropriate pelvic architecture is present, uterine outflow blockage is suspected. If aberrant pelvic morphology is identified, this may imply androgen insensitivity throughout fetal life or Müllerian agenesis.
This patient has primary amenorrhea — no beginning of menses in a female older than 16 years. This disorder may occur with or without other indicators of puberty and most usually happens as a result of anatomic, hormonal, or genetic abnormality. Anatomic causes include congenital lack of the uterus or vagina, presence of vaginal septum or imperforate hymen, blocked/narrowed cervix, or Müllerian agenesis. Hormonal reasons include pituitary (LH, FSH), ovarian malfunction, or androgen insensitivity. Genetic abnormalities include Turner’s syndrome (45 XO). If secondary sex traits are not present, gonadotropins (FSH, LH) are tested first. If levels are low, hypogonadotropic hypogonadism is present. If FSH and LH are excessive (hypergonadotropic hypogonadism), unresponsiveness of tissues (premature ovarian failure or Turner’s syndrome) is suspected. If secondary sex traits are present (as in the patient in the vignette), ultrasonography assessment of pelvic organs is indicated. If appropriate pelvic architecture is present, uterine outflow blockage is suspected. If aberrant pelvic morphology is identified, this may imply androgen insensitivity throughout fetal life or Müllerian agenesis.
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Pathology -Secondary Amenorrhea
In secondary amenorrhea the female patient has had normal menstruation that has ended for some reason.
The most prevalent reason for secondary amenorrhea is pregnancy, and this should be examined in all patients, even if sexual activity is denied. After pregnancy has been ruled out, TSH and prolactin levels should be evaluated, as hypothyroid conditions and hyperprolactinemia are typical reasons of monthly irregularity or cessation. Other causes include excessively low levels of gonadotropins (pituitary tumor) or abnormally high levels of these same hormones (hypergonadotropic hypogonadism found in ovarian failure). Two common causes of normogonadic secondary amenorrhea include outlet blockage and PCOS. Outflow obstruction may develop owing to uterine scarring from infection, obstructive polyps, or cervical stenosis. PCOS is the most common cause of hyperandrogenic chronic anovulation disease. While the primary etiology of PCOS is uncertain, insulin insensitivity is thought to have a role. Hypothalamic amenorrhea is a disorder linked with anomalies in GnRH secretion and disruption of the hypothalamic–pituitary–ovarian axis. The syndrome is commonly induced by extreme weight loss, activity, or stress and may be found in female athletes with lower than normal percentage of body weight. The mechanism of how stress or weight loss impacts GnRH secretion is unknown. Menses will normally return if a healthy body weight is achieved.
In secondary amenorrhea the female patient has had normal menstruation that has ended for some reason.
The most prevalent reason for secondary amenorrhea is pregnancy, and this should be examined in all patients, even if sexual activity is denied. After pregnancy has been ruled out, TSH and prolactin levels should be evaluated, as hypothyroid conditions and hyperprolactinemia are typical reasons of monthly irregularity or cessation. Other causes include excessively low levels of gonadotropins (pituitary tumor) or abnormally high levels of these same hormones (hypergonadotropic hypogonadism found in ovarian failure). Two common causes of normogonadic secondary amenorrhea include outlet blockage and PCOS. Outflow obstruction may develop owing to uterine scarring from infection, obstructive polyps, or cervical stenosis. PCOS is the most common cause of hyperandrogenic chronic anovulation disease. While the primary etiology of PCOS is uncertain, insulin insensitivity is thought to have a role. Hypothalamic amenorrhea is a disorder linked with anomalies in GnRH secretion and disruption of the hypothalamic–pituitary–ovarian axis. The syndrome is commonly induced by extreme weight loss, activity, or stress and may be found in female athletes with lower than normal percentage of body weight. The mechanism of how stress or weight loss impacts GnRH secretion is unknown. Menses will normally return if a healthy body weight is achieved.
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Symptoms and Signs – Differential Diagnosis of Complement deficiency
Congenital e.g. C1 esterase (C1 inhibitor) deficiency (normal C3, reduced C4)
Acquired
Reduced C3 and C4:
SLE, mixed cryoglobulinaemia
Subacute bacterial endocarditis
Serum sickness
Increased Loss/reduced synthesis: malnutrition, nephrotic syndrome, burns, liver failure
Reduced C3
Mesangiocapillary glomerulonephritis, partial lipodystrophy
Gram -ve (endotoxic) shock
Increased C3 and/or C4
Acute phase response
Congenital e.g. C1 esterase (C1 inhibitor) deficiency (normal C3, reduced C4)
Acquired
Reduced C3 and C4:
SLE, mixed cryoglobulinaemia
Subacute bacterial endocarditis
Serum sickness
Increased Loss/reduced synthesis: malnutrition, nephrotic syndrome, burns, liver failure
Reduced C3
Mesangiocapillary glomerulonephritis, partial lipodystrophy
Gram -ve (endotoxic) shock
Increased C3 and/or C4
Acute phase response
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Symptoms and Signs – Differential Diagnosis of Reduced Consciousness
Hypoglycaemia
Hypoxia: cardiac arrest, shock (hypovolaemic, septic), respiratory failure
Infection: meningitis, encephalitis
Inflammation (demyelination)
Toxic: drugs e.g. opiates, alcohol, anxiolytics, antidepressants
Trauma (head injury)
Tumour (increased intracranial pressure)
Vascular: intracranial haemorrhage/infarction
Metabolic: liver failure, renal failure, electrolyte (Na+, K+, Ca2+, Mg2+)
disturbances, endocrinopathies e.g. myxoedema coma, vitamin deficiencies
(e.g. thiamine, B12), hypothermia
Hypoglycaemia
Hypoxia: cardiac arrest, shock (hypovolaemic, septic), respiratory failure
Infection: meningitis, encephalitis
Inflammation (demyelination)
Toxic: drugs e.g. opiates, alcohol, anxiolytics, antidepressants
Trauma (head injury)
Tumour (increased intracranial pressure)
Vascular: intracranial haemorrhage/infarction
Metabolic: liver failure, renal failure, electrolyte (Na+, K+, Ca2+, Mg2+)
disturbances, endocrinopathies e.g. myxoedema coma, vitamin deficiencies
(e.g. thiamine, B12), hypothermia
