Endocrine System
A 28-year-old woman presents to your clinic complaining of amenorrhea and fatigue over the past 3–4 months. A pregnancy test is negative; however, she tells you that she has a 6-month-old child, whose birth was complicated by severe hemorrhage. Further evaluation reveals loss of pubic hair, delayed deep tendon reflexes, and a blood pressure of 90/50 mm Hg. When blood tests reveal decreased levels of FSH, LH, TSH, and ACTH, you inform her that she will have to be on hormone replacement therapy for the rest of her life.
Hypopituitarism
C6
A 59-year-old man presents to your office with a productive cough and dyspnea. He has smoked heavily for many years and works in construction. A CT scan reveals interstitial lung fibrosis and calcified pleural plaques. You inform him that his condition has placed him at great risk for both bronchogenic carcinoma and malignant mesothelioma of the pleura.
Abestosis
C9
A 40-year-old HIV-positive man is admitted to the hospital complaining of generalized edema and fatigue. A complete history reveals that he is a habitual IV drug user. Serum studies show evidence of renal insufficiency and hypoalbuminemia, and urine studies show proteinuria and microscopic hematuria. You suspect that his current presentation is related to his HIV and you prepare the patient for a renal biopsy to determine the exact diagnosis.
Focal Segmental Glomerulosclerosis
Etiology and Epidemiology
Often idiopathic, but also has been associated with heroin use, morbid obesity, reflux nephropathy, sickle cell disease, interferon treatment, and HIV infection.
Most often occurs in older patients.
Pathology
Light microscopy: Sclerosis within capillary tufts of deep juxtaglomerular glomeruli with focal distribution (involves some, but not all, glomeruli) and segmental distribution (involves only a part of the glomerulus); hyalinosis (deposition of hyaline masses) is also seen.
Immunofluorescence: IgM, C3, and C1 can be seen in sclerotic lesions.
Electron microscopy: Fusion of epithelial foot processes.
Clinical Manifestations
Nephrotic syndrome with edema and proteinuria; more severe disease is seen in HIV and IV drug users.
Lab findings: 80% have microscopic hematuria at presentation.
Treatment and Prognosis
Corticosteroids; in steroid-resistant patients, treatment with immunomodulators, such as cyclosporine or tacrolimus, can be considered; ACE inhibitors (reduce urinary protein loss).
Most patients tend to progress to ESRD in 5–10 years, although the course is variable.
An 82-year-old woman is brought to your clinic by her son and daughter. They tell you that she has been very forgetful lately and has twice wandered out of her house and gotten lost, requiring the police to bring her back. Upon speaking with the woman, you note that her short-term memory is compromised and that she has trouble finding the words to express what she wants to say. An MRI of the brain does not reveal any evidence of a stroke. You suspect that a biopsy of this woman’s brain would reveal neuritic plaques and neurofibrillary tangles.
Alzheimer Disease
Etiology and Epidemiology
Etiology unknown, but theories involve abnormal expression of amyloid gene, resulting in increased Aβ protein, deficiency of choline acetyltransferase leading to decreased acetylcholine levels, or atrophy of the nucleus basalis of Meynert. Familial Alzheimer disease involves mutations in amyloid precursor protein (APP) gene on chr 21, mutations in presenilin genes (chr 1,14), and the β4 allele of apolipoprotein E (chr 19).
Most common cause of dementia in the elderly.
Pathology
Gross: Cortical atrophy of brain with widening of sulci and ventricles.
Microscopic: Neurofibrillary tangles composed of tau protein within cytoplasm, which displace nucleus; neuritic plaques (spherical cluster with Aβ protein core and peripheral astrocytes); amyloid angiopathy; Hirano bodies (eosinophilic bodies in hippocampal cells); granulovacuolar degeneration (cytoplasmic vacuoles in hippocampal cells).
Clinical Manifestations
Dementia presenting with progressive memory disturbances, disorientation, aphasias, visuospatial deficits, loss of motor skills, or incontinence.
Treatment and Prognosis
Donepezil (acetylcholinesterase inhibitor) or memantine (NMDA receptor antagonist) to slow progression.
Progressive disease with no cure.
Notes
Vascular dementia occurs as a result of chronic ischemia or infarcts to the brain cortex/subcortex, which is classically seen as lacunar infarcts on imaging.
A 24-year-old African-American man presents to your office complaining of irregular depigmented patches on his hands and around his mouth. He has recently been diagnosed with Hashimoto thyroiditis. A skin biopsy reveals no melanin pigment as well as an absence of melanocytes. You recommend that he use copious sunscreen because his condition puts him at a greater risk for skin cancers.
Albinism and Vitiligo
Etiology
Albinism: Inherited inability of melanocytes to synthesize melanin, either owing to tyrosinase deficiency or deficiency in uptake of tyrosine into the melanocyte; may be related to defective migration of neural crest cells (melanocytes are derived from neural crest ectoderm).
Vitiligo: Acquired loss of melanocytes, possibly caused by an autoimmune reaction or to melanocyte damage by toxic intermediates of melanin synthesis; associated with autoimmune diseases (Addison disease, Hashimoto thyroiditis, Grave disease, pernicious anemia).
Pathology
Albinism: Can involve the eyes (ocular albinism) or the skin and hair (oculocutaneous albinism); melanocytes present in skin.
Vitiligo: Absence of melanocytes in skin.
Clinical Manifestations
Albinism: Hypopigmentation involving the eyes, skin, and hair; may lead to loss of vision.
Vitiligo: Flat, irregular lesions of pigment loss usually involving hands, axillae, or skin around eyes and mouth.
Treatment
Albinism: No cure; sun protection is necessary.
Vitiligo: Topical corticosteroids; sun protection.
A 32-year-old woman presents to your office complaining of a milky discharge from both her nipples. Upon further questioning, you discover that her menstrual period has become extremely irregular and that her last menstruation was over 7 months ago. The laboratory reports a negative pregnancy test; however, this patient does have increased prolactin levels and decreased LH and FSH levels. You decide to send this patient for a MRI of her brain.
Prolactinoma
C7
A 49-year-old man presents to your clinic complaining of mild shortness of breath over the past year. He does not smoke, although he has worked in a glass-manufacturing factory for over 20 years. A CXR reveals eggshell calcification of the hilar lymph nodes. You make a diagnosis and suggest that he have a PPD placed because his condition is associated with increased susceptibility to tuberculosis.
Pneumoconiosis
C8
A 60-year-old man with a 20-year history of type 2 diabetes mellitus presents for a nephrology consult after his primary care physician found a progressive increase of proteinuria in recent laboratory studies. These laboratory studies also showed an elevated creatinine of 2.5 mg/dL and hyperlipidemia. On physical examination, the patient has bilateral diabetic retinopathy and 1+ edema in both legs. You start the patient on an ACE inhibitor and you suspect that a renal biopsy would show Kimmelstiel-Wilson nodules.
Diabetic Nephropathy
Etiology and Epidemiology
Associated with long-standing diabetes.
Type 1 diabetes carries 30%–40% chance of diabetic nephropathy after 20 years; type 2 diabetes carries 15%–20% chance after 20 years; however, because there are more patients with type 2 diabetes, ESRD is more prevalent among type 2 diabetics.
There is a higher risk of developing diabetic nephropathy among men, African Americans, and Native Americans with diabetes.
Pathology
Light microscopy: Increase in mesangial matrix from nonenzymatic glycation, resulting in either diffuse glomerulosclerosis (diffusely distributed increase in mesangial matrix) or nodular glomerulosclerosis (Kimmelstiel-Wilson nodules: nodular accumulations of mesangial matrix material).
Electron microscopy: Striking increase in GBM thickening (increased permeability).
Clinical Manifestations
Nephrotic syndrome; diabetic retinopathy is invariably present with possible neuropathy.
Lab findings: Microalbuminuria (early sign), proteinuria (late sign).
Treatment and Prognosis
Strict glycemic control; treatment of hypertension and microalbuminuria with ACE inhibitors during early stages to slow progression.
Often progresses to ESRD and dialysis.
Notes
Diabetic nephropathy is the most common cause of ESRD in the United States.
A 62-year-old woman is brought to your clinic by her husband. He tells you that his wife has become irritable and aggressive lately. He reports that he caught her shoplifting twice in the past month and he has also noticed that she sometimes misnames common household objects. Upon speaking with the patient, you note that she is impatient and socially inappropriate in her responses. You fear that this patient may be suffering from a form of dementia, which is associated with the presence of round, silver-staining, neurofilamentous bodies within the neuronal cytoplasm, so you refer her to a neurologist for further evaluation.
Huntington Disease
Etiology and Epidemiology
Autosomal dominant disorder associated with increased number of CAG repeats in Huntington disease gene on chromosome 4.
Tends to manifest between the ages of 20 and 50.
Pathology
Gross: Atrophy of caudate nucleus and putamen; may also see atrophy of globus pallidus and frontal lobe; dilatation of lateral and third ventricles.
Microscopic: Loss of striatal neurons (GABAergic neurons); fibrillary gliosis.
Clinical Manifestations
Progressive disorder that manifests with chorea (involuntary jerky movements), cognitive impairment, and mood disturbances.
Eventually progresses to severe dementia.
Treatment and Prognosis
Symptomatic treatment for dyskinesia and mood disturbances.
Usually fatal within 15–20 years of diagnosis.
Notes
Huntington disease, as well as fragile X syndrome and myotonic dystrophy, demonstrates anticipation, a phenomenon in which the number of repeats increases with each generation and results in more severe disease manifestations.
A baby girl is born to a 46-year-old woman. The baby has multiple abnormalities, including polydactyly, a cleft lip and palate, and microcephaly, causing you to suspect that the baby most probably also has congenital heart and renal defects. You decide to send a sample of the baby's blood for chromosomal analysis, but you begin to worry that the baby's prognosis is not good.
Edwards Syndrome and Patau Syndrome
A 63-year-old woman presents to your office complaining of generalized bone pain. While discussing her health further, you discover that she is also suffering from polyuria, constipation, and muscular weakness. A bone densitometry study reveals a significant loss of cortical bone. You order laboratory studies, which reveal increased calcium levels, increased PTH levels, increased alkaline phosphatase, and decreased phosphate levels. You believe that a parathyroid biopsy will reveal polygonal chief cells and larger oxyphil cells and that a bone biopsy would reveal brown tumors.
Primary Hyperparathyroidism
Etiology
Caused by PTH adenoma, PTH hyperplasia, PTH carcinoma, or production of PTH-like hormone by tumors (especially squamous cell bronchogenic carcinoma).
Associated with MEN I and MEN IIA.
Pathology
Parathyroid gland: Parathyroid adenoma: circumscribed nodule composed of uniform, polygonal chief cells along with a few larger oxyphil cells.
Bone: Osteitis fibrosa cystica: cystic spaces filled with fibrous tissue (brown tumors), owing to increased osteoclast activity.
Clinical Manifestations
Bone pain due to osteitis fibrosa cystica; nephrocalcinosis; peptic ulcers; constipation; weakness; altered mental status; polyuria.
Lab findings: Hypercalcemia; increased PTH levels; increased serum alkaline phosphatase; decreased serum phosphate.
Treatment
Surgical removal of the abnormal glands in patients with renal failure, osteoporosis, or significant hypercalcemia.
Notes
Other causes of hypercalcemia include cancer originating in or metastatic to the bone, multiple myeloma, sarcoidosis, milk alkali syndrome, Paget disease of the bone, hyperthyroidism, and vitamin D intoxication.
C18
List Diagnosis and pathophysiology**
An 8-year-old girl is brought into an urgent-care clinic complaining of shortness of breath. Her past medical history is significant for multiple allergies. Upon physical examination, you hear expiratory wheezes and you observe that the patient is using her accessory muscles of respiration. You decide to administer an inhaled β₂-adrenergic agonist for relief of her symptoms.
Asthma
Pathology and Pathophysiology
Pathophysiology: Hypersensitivity of bronchial airways results in symptomatic bronchospasm.
Lung: Hypertrophy of bronchial smooth muscle; hyperplasia of bronchial submucosal glands; mucous plugs containing Curschmann spirals and Charcot-Leyden crystals.
C3
A 67-year-old male with a past medical history of long-standing uncontrolled hypertension presents to your clinic for establishment of care. He states that he has been feeling generally well, although he has episodes of headaches and lower extremity swelling from time to time. Physical examination is notable for a BP of 174/106 mm Hg. A routine ECG demonstrates changes consistent with left ventricular hypertrophy. When laboratory studies demonstrate elevated BUN and creatinine levels, you fear that the patient is at a risk for progressing to ESRD if his hypertension is not aggressively controlled.
Hypertensive Nephrosclerosis
Etiology and Epidemiology
Associated with long-standing, poorly controlled hypertension.
There is a higher risk of developing hypertensive nephrosclerosis in African Americans and patients aged > 45.
Pathology
Gross: Shrunken and scarred kidneys.
Light microscopy: Mesangial cell proliferation with a shrunken glomerular tuft; sclerosis and hyalinization of afferent arterioles; interstitial fibrosis; eventual development of secondary focal segmental glomerulosclerosis.
Clinical Manifestations
Nephrotic syndrome with variable proteinuria, hematuria; hypertension; hypertensive retinopathy and left ventricular hypertrophy are usually present as well.
Treatment and Prognosis
Aggressive treatment of hypertension including ACE inhibitors; dialysis and/or transplant for patients with ESRD.
A 53-year-old male presents to the emergency room with altered mental status. He has a past medical history significant for alcohol abuse. He was discharged from the hospital 4 days ago after presenting with severe hyponatremia (Na 115 mEq/L). In reviewing the laboratory studies from his last hospitalization, you note that his sodium levels increased from 115 mEq/L to 138 mEq/L within 36 hours. On exam, the patient has dysarthria and significant weakness of all four extremities. You immediately call for a neurology consult, but you fear that he may end up with lasting deficits from his condition.
Central Pontine Myelinolysis (CPM)
Etiology
Most commonly caused by rapid correction of severe or chronic hyponatremia, but has also been reported after liver transplantation, hyperglycemic states, and in cases of severe burns.
Pathophysiology
In response to hyponatremia, osmolytes efflux from CNS cells to the CSF to adapt to the decrease in serum tonicity. With rapid correction of hyponatremia, brain cells are unable to reabsorb osmolytes quickly enough, leading to cellular damage, particularly within astrocytes. Cellular damage then leads to demyelination of white matter. When demyelination is confined to the pons, CPM results.
Clinical Manifestations
Symptoms present 3–5 days after rapid correction of hyponatremia and include pseudobulbar palsy leading to dysarthria and dysphagia, spastic paralysis, and delirium or even coma. It may also present with locked-in syndrome.
Treatment
Supportive care; prevention by keeping rate of sodium correction to no more than 8–10 mEq/L/day.
Notes
CPM is a form of Osmotic Demyelination Syndrome. Osmotic demyelination syndrome refers to demyelination that occurs in extra pontine regions, such as the cerebellum, midbrain, and thalamus.
**List Diagnosis, Pathology and Pathophysiology
A 2-year-old girl is brought to your pediatric cardiology clinic for evaluation of a murmur heard by her primary care doctor. In speaking with the girl’s father, he tells you that she is healthy and active. On physical examination, you note that the girl is well nourished and appropriately sized for her age. You do detect a harsh, holosystolic murmur at the left lower sternal border, with no evidence of right ventricular strain. You suspect that the child has the most common congenital cardiac anomaly and you order an echocardiogram to confirm your suspicions. In the meantime, you reassure the girl’s father that her anomaly is likely minor and will require no treatment.
Ventricular Septal Defect
Etiology
Most common congenital cardiac anomaly. Often seen in conjunction with other congenital cardiac anomalies (eg, tetralogy of Fallot, TGA); associated with fetal alcohol syndrome, Down syndrome, and maternal diabetes.
Pathology and Pathophysiology
Pathology: Defect in ventricular septum allowing communication between right and left ventricles caused by failure of fusion of the interventricular septum with the aortic septum. There are several variants, including membranous ventricular septal defect (VSD) (90%), infundibular VSD, and muscular VSD.
Pathophysiology: Initially, left-to-right shunt is present, due to lower pulmonary vasculature resistance as compared to systemic vasculature resistance. As a shunt persists, the chronic volume overload to the right side of the heart results in increasing pulmonary vascular resistance, with eventual reversal of the shunt to right to left.
Clinical Manifestations
Small VSDs are generally asymptomatic. In infants, moderate to large VSDs may present as failure to thrive or sweating during feeding. In the older population, patients may present with dyspnea and exercise intolerance.
Physical examination may demonstrate a harsh holosystolic murmur at left lower sternal border (if VSD is large) and RV heave.
Complications include pulmonary hypertension, heart failure, and arrhythmias.
Treatment
Small VSDs may close spontaneously. Closure is indicated for large VSDs if the patient has developed symptoms or evidence of volume overload on echocardiography.
Notes
Eisenmenger syndrome refers to cyanosis occurring in adulthood owing to a shunt shift from left to right to right to left. It is caused by uncorrected, physiologically significant VSDs, ASDs, and PDAs.
**List Diagnosis & Treatment
A 65-year-old man is brought to the emergency department by his daughter because of confusion. He was recently diagnosed with small-cell bronchogenic carcinoma and the plan had been to begin chemotherapy in the near future. Laboratory tests reveal significantly decreased serum sodium levels, decreased serum osmolality, and increased urine osmolality. As you admit him to the hospital, you suspect that this patient’s condition is directly related to his lung cancer.
Syndrome of Inappropriate ADH (SIADH)
Etiology
Causes include pulmonary disorders (eg, COPD, pneumonia), intracranial pathology (eg, trauma, hemorrhage, stroke), pharmacologic agents (eg, antipsychotics, chemotherapy), or pain; may also be caused by ectopic ADH production by small-cell bronchogenic carcinoma and other tumors.
Pathophysiology
Increased ADH secretion results in water retention in the collecting duct of the nephron. Water retention leads to dilution of serum electrolytes, especially sodium, and subsequently decreased serum levels of electrolytes and serum osmolality.
Clinical Manifestations
Fatigue and confusion caused by decreased serum sodium; euvolemia.
Lab findings: Hyponatremia; decreased serum osmolality; increased urine osmolality.
Treatment
Fluid restriction; vasopressin receptor blockers (eg, demeclocycline, tolvaptan); hypertonic saline if hyponatremia is severe.
C10
**List Diagnosis, Pathology and Pathophysiology
A 63-year-old man is hospitalized for a severe case of lobar pneumonia with sepsis. Within the first 24 hours of his hospitalization, he develops worsening respiratory failure and requires intubation. A CXR reveals bilateral patchy opacities. He becomes progressively hypoxemic despite increased oxygen delivery via the ventilator. You continue to treat the patient's pneumonia, but you worry that he will have up to a 30%-60% mortality rate given his current condition.
Acute and Neonatal Respiratory Distress Syndrome
- Pathology and Pathophysiology
ARDS: Damage to alveolar capillary walls and alveolar walls by cytokines and endotoxin leads to increased vascular permeability and decreased surfactant, which leads to pulmonary edema and alveolar collapse, pulmonary hypertension.
Gross: Heavy, red lung.
Microscopic: Intra-alveolar edema and inflammation with hyaline membranes; if nonfatal, results in chronic scars.
C7
**List Diagnosis, Pathology and Pathophysiology
A 10-year-old girl presents to your pediatric urgent care clinic complaining of eye swelling. In review of her records, you note that the child was seen 3 weeks ago in clinic for a chief complaint of sore throat. Upon taking a history and performing a physical, you find that the patient has pronounced periorbital edema, has been urinating very little despite adequate fluid intake, and has a blood pressure of 150/90 mm Hg. Laboratory findings include azotemia, hematuria, red cell casts in the urine, and an elevated ASO antibody titer. You reassure the parents that their child’s condition will likely resolve on its own.
Rapidly Progressive (Crescentic) Glomerulonephritis
Etiology
Type 1: Idiopathic or Goodpasture syndrome.
Type 2 (immune complex): Idiopathic; postinfectious causes; SLE; IgA nephropathy; Henoch-Schönlein purpura.
Type 3 (negative or pauci-immune type): Idiopathic; granulomatosis with polyangiitis; eosinophilic granulomatosis with polyangiitis; microscopic polyangiitis.
Pathology
Light microscopy: Formation of crescent-moon shape between Bowman capsule and glomerular tuft, resulting from deposition of fibrin, plasma proteins, and macrophages in the Bowman space and from proliferation of parietal epithelial cells of the Bowman capsule.
Immunofluorescence:
Type 1 — linear pattern due to antibodies against alveolar and glomerular basement membranes;
Type 2 — granular pattern due to immune complex deposition;
Type 3 — no depositions generally seen.
Clinical Manifestations
Nephritic syndrome with hematuria, hypertension, and azotemia.
Signs and symptoms are specific to each etiology (eg, hemoptysis and anti-GBM antibodies in Goodpasture syndrome).
Treatment and Prognosis
Treat with diuretics and ACE inhibitors; immunosuppression with steroids or cytotoxic agents as appropriate for underlying cause; plasmapheresis for Goodpasture syndrome; may require dialysis or transplant.
Patients generally have a rapid course to end-stage renal failure requiring dialysis.
**List Diagnosis, Pathology and Pathophysiology
A 12-year-old boy is brought to your pediatrics clinic by his mother because of an unsteady gait. While taking a history, you learn that the patient has had a long history of clumsiness with frequent falls and three episodes of sprained ankles in the last year alone. He states that his clumsiness has worsened over the last year or so and now he feels as if he has trouble buttoning his jacket or typing on the computer. Physical examination reveals evidence of pes cavus deformity and mild scoliosis, as well as decreased deep tendon reflexes and a decreased vibratory sensation. You tell the patient that his symptoms are likely reflective of a relatively common inherited neuropathy and you refer him to neurological clinic for further treatment.
Charcot–Marie–Tooth Disease (Hereditary Motor and Sensory Neuropathy)
Etiology
Inherited peripheral neuropathy, most commonly autosomal dominant.
Caused by mutations affecting myelin or axonal proteins (most commonly PMP22 gene duplication).
Pathology and Pathophysiology
Progressive demyelination of peripheral nerves leading to slowed nerve conduction velocity.
Repeated cycles of demyelination and remyelination produce “onion bulb” formations around nerves.
Clinical Manifestations
Distal muscle weakness and atrophy beginning in the lower extremities (“stork leg” appearance).
Foot deformities including pes cavus and hammer toes.
Frequent ankle sprains and falls.
Loss of deep tendon reflexes.
Decreased vibratory and proprioceptive sensation.
Later involvement of the hands causing difficulty with fine motor tasks (e.g., buttoning clothing).
Mild scoliosis may be present.
Treatment
No cure.
Supportive care including physical therapy, orthopedic bracing, and occupational therapy.
Notes
Charcot–Marie–Tooth disease is one of the most common inherited neurologic disorders.
** List Diagnosis, Etiology, Pathology, Clinical Manifestations, and Treatment
A 40-year-old woman with a history of SLE presents to your nephrology office for evaluation of renal insufficiency. Review of systems is notable for increased swelling in her legs. Recent laboratory studies show proteinuria, hypoalbuminemia, and hyperlipidemia. You suspect that a renal biopsy would demonstrate immune complex deposition on electron microscopy as well as a "spike-and-dome" appearance on silver methenamine stain.
Membranous Nephropathy
Etiology and Epidemiology
Primary disease (80%) is usually mediated by antibodies against the M-type phospholipase A₂ receptor.
Secondary disease (20%) is associated with infections (eg, hepatitis B and C, HIV, syphilis, malaria), autoimmune diseases (eg, SLE class V, RA, Sjögren syndrome), drugs (eg, gold salts, penicillamine, NSAIDs), or malignancy (eg, lung, prostate, hematologic, colon).
Incidence is highest in adults.
Pathology
Light microscopy: Diffuse capillary wall thickening and basement membrane thickening.
Immunofluorescence: Granular pattern of IgG or C3 deposits (lumpy-bumpy).
Electron microscopy: Electron-dense immune complex deposition in subepithelial locations within the basement membrane of glomerular capillary walls.
Silver methenamine stain: A spike-and-dome appearance resulting from the extension of basement membrane between and around the immune deposits (spikes = basement membrane, domes = immune complex deposits).
Clinical Manifestations
Nephrotic syndrome with edema, proteinuria, and anorexia often accompanied by azotemia.
Hematuria can also be seen in 50% of patients.
Complications include chronic kidney disease and renal vein thrombosis.
Treatment and Prognosis
Up to 70% of patients will experience spontaneous remission; otherwise, cyclophosphamide in combination with steroids or other immunomodulators can be used (poor response to prednisone alone in primary disease); ACE inhibitors (reduce urinary protein loss); renal transplant for severe cases.
** List Diagnosis, Etiology, Pathology, Clinical Manifestations, and Treatment
A 42-year-old woman presents to your office complaining of headaches. After taking a full history, you learn that she has been extremely thirsty lately and that she has been urinating frequently. A neurologic examination is unremarkable, but laboratory tests reveal increased serum osmolality and hypernatremia. You decide that further endocrinologic evaluation will be necessary to determine the etiology of her disorder.
Diabetes Insipidus
Etiology
Central diabetes insipidus: Deficiency of ADH secretion from the posterior pituitary; can be idiopathic or caused by hypothalamus damage (neoplastic or traumatic) or histiocytosis.
Nephrogenic diabetes insipidus: Defective ADH receptors in the kidney; causes include familial deficiency, drugs (eg, lithium; demeclocycline), hypercalcemia, or tubulointerstitial kidney disease.
Pathophysiology
A deficiency in ADH or the inability of the kidney to sense ADH results in the inability to retain water, and thus increased urine output. Lack of water retention leads to an increase in serum osmolality, which stimulates thirst receptors in the brain and the posterior pituitary to release more ADH.
Clinical Manifestations
Polydipsia and polyuria; seizures; headaches; signs of dehydration.
Lab findings: Increased serum osmolality; hypernatremia; decreased urinary specific gravity.
Treatment
Desmopressin for central diabetes insipidus.
Low-sodium diet and thiazide diuretic for nephrogenic diabetes insipidus.
C11
** List Diagnosis, Etiology, Pathology, Clinical Manifestations, and Treatment
A 63-year-old man presents to your office complaining of worsening shortness of breath over the past year. You know that this patient has smoked two packs of cigarettes a day for the past 45 years. As you are talking to the patient, you notice that his chest is barrel shaped and that he is breathing carefully through pursed lips. Using a spirometer, you determine that he has a decreased FEV₁/FVC ratio and an increased TLC. You tell the patient that it is imperative that he stop smoking and you prescribe him a tiotropium inhaler.
Emphysema
-Etiology
Associated with smoking and hereditary α₁-antitrypsin deficiency.
-Pathology and Pathophysiology
Pathophysiology: Enzymes (elastase) destroy elastin in alveolar wall, unless neutralized by α₁-antitrypsin; smoking inactivates α₁-antitrypsin and attracts neutrophils and macrophages (source of elastase). This leads to loss of elastic recoil properties and air trapping upon exhalation.
Gross pathology: Enlargement of air spaces; destruction of alveolar wall; two patterns seen:
(1) Centriacinar: respiratory bronchioles dilated especially in the upper lobes, seen in smokers;
(2) Panacinar: entire acinus is dilated in entire lung especially in lower lobes, seen with α₁-antitrypsin deficiency.
-Clinical Manifestations
“Pink puffers” (slowing of forced expiration through pursed lips); dyspnea; cough; cyanosis; tachycardia; barrel-shaped chest; distant breath sounds; use of accessory respiratory muscles.
Complications include pneumothorax caused by bullae rupture, chronic bronchitis, and cor pulmonale.
Imaging: Hyperinflation and bullae with increased AP diameter and flattened diaphragm on CXR.
PFT findings: Hypoxia; increased residual volume and TLC; decreased FEV₁/FVC ratio.
Treatment
Smoking cessation; oxygen; inhaled anticholinergics and β-agonists; inhaled steroids.
Notes
Emphysema is a chronic obstructive pulmonary disease (COPD).
Hereditary α₁-antitrypsin deficiency also causes hepatic cirrhosis.
C2
** List Diagnosis, Etiology, Pathology, Clinical Manifestations, and Treatment
A 15-year-old boy presents to the emergency room complaining of blood in his urine. Upon taking a complete history, you learn that he has also been suffering from fevers, myalgias, and arthralgias for the last 2 days. Laboratory studies confirm the presence of red blood cells in the urine, but also reveal increased serum IgA levels and normal serum complement levels. You begin him on prednisone and you suspect that he is afflicted with the most common form of acute glomerulonephritis in the United States.
IgA Nephropathy (Berger Disease)
Etiology and Epidemiology
Primary renal disease of IgA deposition in the glomerular mesangium that can manifest after infection (viral URI, GI infection, flu-like syndrome) or can be a component of Henoch-Schönlein purpura.
Most commonly seen in young adults with men affected more often than women.
Pathology
Light microscopy: Focal proliferative glomerulonephritis with diffuse mesangial widening.
Electron microscopy and immunofluorescence: Mesangial immune complex deposits of IgA.
Clinical Manifestations
Presents with recurrent hematuria (red or cola-colored urine) 1–2 days after an upper respiratory or GI infection. Hypertension, fatigue, and mild proteinuria may be present.
Lab findings: Increased serum IgA level (50% of cases); normal serum complement levels; RBCs in urinalysis.
Treatment and Prognosis
ACE inhibitors for proteinuria; steroids or immunosuppressants for selected cases.
20%–30% of patients progress to end-stage renal failure over 20–30 years.
Notes
Berger disease is the most common form of acute glomerulonephritis in the United States and is also prevalent in Asia.
** List Diagnosis, Etiology, Pathology, Clinical Manifestations, and Treatment
A 29-year-old man presents to the emergency room complaining of muscle weakness. He tells you that the weakness began in his calves and has now ascended to involve his thighs, hips, torso, and arms. Upon directed history, you learn that he recently recovered from a flu-like illness. Physical examination reveals symmetrical muscle weakness in all limbs and absent deep tendon reflexes. A lumbar puncture demonstrates an albumin-cytologic dissociation of the CSF. You admit this patient to the ICU for observation as you fear that he may need mechanical respiratory support for his condition.
Acute Inflammatory Demyelinating Polyneuropathy (AIDP)
Etiology
Autoimmune response, often thought to be triggered by infection (eg, Zika virus; influenza; EBV; HIV; C. jejuni), although cases associated with surgery, pregnancy, and post-vaccination have been reported.
Pathology and Pathophysiology
Pathophysiology: Immune reaction that results in demyelination of peripheral nerves.
Peripheral nerves: Endoneurial and perivenular infiltration by lymphocytes and macrophages; segmental demyelination.
Clinical Manifestations
Ascending muscle weakness and paralysis beginning in distal lower limbs; absent deep tendon reflexes; abnormal autonomic function (dysrhythmias, labile blood pressure).
Can progress to respiratory failure or become chronic (chronic inflammatory demyelinating polyradiculoneuropathy).
Lab findings: Lumbar puncture shows albumin-cytologic dissociation of CSF (large protein content increase accompanied by only a mild cell count increase).
Treatment
Plasmapheresis; IV immunoglobulin; supportive care (respiratory support until recovery).
Notes
Guillain-Barré syndrome is the most common form of AIDP.
Postinfectious encephalitis can follow viral illnesses (eg, chicken pox, rubella, measles, mumps) and is characterized by transient, widespread demyelination.
** List Diagnosis, Etiology, Pathology, Clinical Manifestations, and Treatment
A fellow medical student suddenly complains that she cannot breathe and within seconds, she is frantically gasping for air. You were about to help her examine a patient and both of you had just put on some latex gloves. You immediately take your and her gloves off and ask the nurse to draw up 1 mg of epinephrine and to have an intubation box ready if needed. You do a quick survey of your colleague and find that she has marked edema of her upper extremities and face. You inject the epinephrine SQ and start an IV so that you can begin to administer a rapid IV infusion of large volumes of saline solution to combat any hypotension and shock. Your fellow medical student has markedly improved within minutes; however, she is admitted to the hospital for further observation.
Hypersensitivity Reactions
Etiology
Type I: IgE-mediated immediate hypersensitivity.
Type II: Antibody-mediated cytotoxic hypersensitivity.
Type III: Immune complex–mediated hypersensitivity.
Type IV: T-cell–mediated delayed hypersensitivity.
Pathophysiology
Type I: Antigen cross-links cell-bound IgE on pre-sensitized mast cells and basophils, causing release of vasoactive amines that cause vasodilation, visceral smooth muscle contraction, vascular permeability, and tissue inflammation.
Type II: IgG or IgM antibody reacts to cell-bound antigens resulting in activation of the complement cascade and destruction or dysfunction of antigen-bound cell.
Type III: IgG or IgM antibody complexes with circulating allergens and deposits in tissue, thereby activating complement cascade and neutrophils.
Type IV: Allergen binds endogenous protein and is presented to T cells. If re-exposed to allergen, memory T cells stimulate inflammatory reaction or cellular destruction.
Clinical Manifestations
Type I: Atopy; anaphylaxis; asthma; allergic rhinitis; local wheal and flare.
Type II: Immune hemolytic anemia; erythroblastosis fetalis; ARF; Goodpasture syndrome.
Type III: Arthus reaction (localized cutaneous and subcutaneous inflammatory response to injected allergen); serum sickness (systemic disease fever, arthralgias, proteinuria, lymphadenopathy, and dermatitis); polyarteritis nodosa; SLE; RA.
Type IV: Allergic contact dermatitis; hypersensitivity pneumonitis; GVHD.
Treatment
Antihistamines; corticosteroids; treatment of specific etiology.