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45 year old woman suffers from difficulty walking. Spinal cord shows symmetric myelin layer vacuolization and axonal degeneration involving the posterior columns and lateral corticospinal tracts. What is causing this patient's condition?

1. "Subacute combined degeneration" due to abnormal myelin synthesis associated with Vitamin B12 deficiency.
2. Damage to the dorsal columns leads to b/l loss of position and vibration sensation (sensory ataxia)
3. Damage to b/l lateral corticospinal tracts leads to UMN signs (spastic paresis, hyperreflexia, +Babinski).
4. Axonal degeneration of peripheral nerves can cause numbness or paresthesias.


Adenoma to carcinoma sequence

1. Inactivation of APC (tumor suppressor gene on chromosome 5) in normal colonic epithelium leads to hyperproliferation.
2. Methylation abnormalities and COX-2 overexpression lead to adenomatous polyps, premalignant lesions with dysplastic mucosa.
3. Additional mutations in K-ras (activation), DCC (inactivation), and p53 (inactivation) lead to further accumulations of genetic abnormalities, which can transform into carcinoma.
4. Accumulation of gene mutations in a stepwise progression to adenocarcinoma is called the "adenoma-to-carcinoma sequence."


Increased activity of which enzyme is most likely to promote recurrent adenoma development?

Cyclooxygenase-2 (COX-2). Increased activity of COX-2 occurs in some forms of colon adenocarcinoma and in inherited forms of polyposis. Patients taking aspirin (a COX inhibitor) regularly have been shown to have lower incidence of adenomas compared to general population.



1. Universal response of CNS to severe damage, involving proliferation of astrocytes (glial hyperplasia) in an area of neuron degeneration leading to a glial scar compensating for volume loss after neuronal death.
2. Proliferating astrocytes have large vesicular nuclei with prominent nucleoli, and contain many fibrils and glycogen granules.
3. After neuronal death, astrocytic processes form a closely connected firm meshwork called a gliotic scar.
4. Shrunken and deeply eosinophilic neurons (red neurons) undergo cell death and are phagocytosed by microglia.


Bilateral ovarian masses removed from a 55 year old Caucasian woman show poorly differentiated cells heavily loaded with mucus

Krukenberg tumor- metastatic gastric adenocarcinoma to the ovarian stroma characterized by mucin-producing, signet-ring neoplastic cells. Can also occur in association with breast, pancreas, or gallbladder primary cancers. Most common type of metastatic ovarian cancer. Breast cancer metastasis to the ovary estimated 6-28% of patients, but most common neoplastic source associated with Krukenberg tumor is stomach.


Virchow's node

Metastasis of gastric carcinoma from gastric wall to the left supraclavicular sentinel node. Frequently the first clinical manifestation of occult gastric cancer.


Sister Mary Joseph nodule

Metastasis of gastric carcinoma to periumbilical region resulting in a subcutaneous mass. If gastric carcinoma left untreated/undiagnosed can cause extensive peritoneal seeding and widespread metastasis to liver and lungs.


Cell cycle checkpoints

1. G1 (synthesis of RNA, protein, lipid, carbohydrate) to S (DNA replication) phase
2. G2 (ATP synthesis) to M (mitosis) phase
3. Checkpoints are regulated by cyclins and cyclin-dependent kinases (CDKs) that screen for DNA damage or abnormalities.
4. Cells with normal DNA are allowed to proceed, cells with damaged DNA trigger DNA repair mechanisms, and if DNA damage is too substantial to be repaired, p53 ("molecular policeman") signals BAX, which inactivates Bcl-2, causing cytochrome C to leak from mitochondria and activate apoptosis (caspases).


Retinoblastoma protein (Rb)

1. Nuclear phosphoprotein (Rb) that regulates G1-->S checkpoint by binding the E2F transcription factor necessary for transition to S phase.
2. E2F is released when Rb is phosphorylated (inactivated) by cyclinD/CDK4 complex.
3. Inactive (hyperphosphorylated) Rb protein releases E2F, allowing cell to proceed through G1-->S checkpoint.
4. Activated (hypophosphorylated) Rb binds E2F, preventing cell cycle progression.
5. Abnormal phosphorylation of Rb results in permanent Rb inactivation, allowing for constitutively free E2F, thereby allowing cells (even those with damaged DNA) to proceed through G1-->S checkpoint and uncontrolled growth.
6. Mutations of Rb protein linked to retinoblastoma, osteosarcoma, breast adenocarcinoma, SCC of the lung, and bladder carcinoma.


Zollinger-Ellison syndrome

Gastrin hypersecretion induces parietal cell hyperplasia, causing visible enlargement of gastric rugal folds on endoscopy. Increased gastric acid secretion caused by excess gastrin causes PUD, hearburn, and diarrhea. Gastrin not only stimulates HCl secretion from parietal cells in fundus/body of the stomach but also has a trophic effect on them.



Produced by S cells of small intestine. Increases bicarbonate production by pancreas and leads to secretion of watery, alkaline pancreatic juice. Also inhibits gastric acid secretion and stimulates pyloric sphincter contraction.



Primarily found in enterochromaffin cells of GI tract, CNS, and platelets. In GI tract, helps to regulate intestinal secretions and peristalsis.



Somatostatin (growth hormone-inhibiting hormone) is secreted by D cells of pancreatic islets and GI mucosa. Has multiple inhibitory effects over GI tract, including decreasing motility, gastrin secretion, pancreatic endocrine/exocrine secretion, and absorption of nutrients.


Transforming growth factor alpha (TGF-α)

Potent stimulator of epithelial growth, secreted by carcinomas, macrophages, and epithelial cells.


Menetrier disease

Overproduction of TGF-α resulting in mucosal-cell hyperplasia with gastric fold enlargement. However, condition causes hypoplasia of parietal/chief cells, resulting in glandular atrophy with reduced gastrin secretion.


Nests of polygonal cells with Congo red-positive deposits in a neck mass

Medullary thyroid carcinoma (MTC) is characterized by extracellular deposits of amyloid formed by calcitonin secreted from neoplastic parafollicular C-cells. Amyloid stains with Congo red.


Neck mass with histology of branching structures with interspersed calcified bodies

Well-differentiated papillary thyroid cancer. Papillary structure with calcifications (psammoma bodies) and large, ground glass, grooved nuclei. Follicular hyperplasia with tall cells is variant of papillary thyroid cancer found in older individuals, more invasive than classic well-differentiated papillary thyroid cancer.


Neck mass with sheets of uniform cells forming small follicles

Presence of colloid-containing microfollicles suggests benign follicular adenoma. Sometimes, benign follicular adenoma can be difficult to distinguish from well-differentiated follicular thyroid cancer, which can also have appearance of normal thyroid follicles. Tip-off is that capsular and vascular invasion only occurs with carcinoma.


Neck mass with pleomorphic giant cell nests with occasional multinucleated cells

Large pleomorphic giant cells seen in anaplastic thyroid cancer.


Most common predisposing condition for native valve infective endocarditis in developed nations

Mitral valve prolapse (with or without mitral regurgitation), responsible for approximately 25-30% of cases of IE in developed nations. Mitral valve is the most common valve affected by infective endocarditis. Microscopic deposits of platelets and fibrin occur spontaneously in individuals with valvular disease 2/2 endocardial injury from turbulent blood flow. These deposits become colonized by microorganisms during episodes of transient bacteremia. Other common factors are valvular sclerosis and mechanical valves.


Most important form of acquired heart disease in children and young adults in developing countries.

Rheumatic heart disease. Remains a frequent cause of IE in developing nations.


Adverse effect of high concentrations of oxygen therapy given for neonatal respiratory distress syndrome?

Retinopathy of prematurity (retrolental fibroplasia). Retinal damage 2/2 neonatal oxygen supplementation. Temporary local hyperoxia in the retina is thought to induce up-regulation of proangiogenic factors such as VEGF upon return to room air ventilation. Retinal vessel neovascularization and possible retinal detachment with blindness may result.


Non-atrophic chronic gastritis

Most often due to H. pylori infection, which primarily affects the antrum but with time may spread to involve the gastric body. Inflammatory infiltrate is primarily composed of neutrophils in the acute phase, but may be characterized by lymphocytes, lymphoid follicles, and plasma cells in chronic H pylori gastritis.


Pathogenesis of centriacinar emphysema associated with chronic smoking

Oxidative injury to the respiratory bronchioles by cigarette smoke activates resident alveolar macrophages followed by inflammatory recruitment of neutrophils into the affected airspaces. Infiltrating neutrophils and activated alveolar macrophages release proteases (eg, elastase, cathepsins, MMPs) that degrade the ECM and generate oxygen free radicals that impair the function of protease inhibitors (eg, A1AT). Protease-antiprotease imbalance leads to acinar wall destruction and irreversible airspace dilation.


Club cells

aka Clara cells. Nonciliated, secretory constituents of terminal respiratory epithelium. Secrete club cell secretory protein and surfactant components. Help to detoxify inhaled substances by cytochrome P450 mechanism.


Type I pneumocytes

Make up over 95% of the inner epithelial lining of the alveoli, these cells are destroyed by acinar wall damage that occurs in emphysema.


Wernicke's aphasia

Wernicke= Word salad. Receptive aphasia (may be fluent aphasia). Impairment in verbal/written language comprehension as well as repetition. Often produced by a lesion in Wernicke's area (located in the auditory association cortex within the posterior portion of superior temporal gyrus, usually in the left temporal lobe), which is supplied by the inferior terminal MCA branches. Superior division of the MCA supplies Broca's area.


Inhibin B

Hormone secreted from Sertoli cells. Stimulated by FSH, and has negative feedback inhibition of FSH release from anterior pituitary. Sertoli cells are present within the seminiferous tubules of the testes. In patients with 1 testicle, mass of Sertoli cells greatly reduced and circulating levels of inhibin B are likely to be low. Low inhibin B will not adequately inhibit FSH secretion, and thus FSH levels will tend to be elevated in males with 1 testicle. Male patient of any age who has only 1 testes requires further evaluation as there is increased cancer risk.


Gonadotropin regulation in males

Pulsatile secretion of GnRH from hypothalamus stimulates release of FSH and LH, which are produced by gonadotroph cells of anterior pituitary. "L"H stimulates release of testosterone from "L"eydig cells of testes. LeyDIG cells DIG testosterone. F"S"H stimulates release of inhibin B from "S"er"T"oli cells of "S"eminiferous "T"ubules. Testosterone has negative feedback inhibition of LH and GnRH secretion. Inhibin B suppresses FSH secretion. Dihydrotestosterone and DHEA also cause LH feedback inhibition.


Zona glomerulosa

1. Think "GFR" and "It gets sweeter as you go deeper."
3. PREGNENOLONE ---> PROGESTERONE (3-beta-hydroxysteroid dehydrogenase)
4. PROGESTERONE ---> 11-DEOXYCORTICOSTERONE (weak MC) (21-hydroxylase)
5. DEOXYCORTICOSTERONE ---> CORTICOSTERONE (weak GC) (11-beta-hydroxylase)
6. CORTICOSTERONE ---> ALDOSTERONE (aldosterone synthase)