pathophysiology of important path Flashcards
(272 cards)
1
Q
What is Sturge-Weber syndrome?
A
Congenital anomaly of neural crest derivatives leading to capillary vascular malformation and ipsilateral leptomeningeal angioma with calcifications
Somatic mosaicism of an activating mutation in one copy of the GNAQ gene is involved.
2
Q
What is a pituitary adenoma?
A
Hyperplasia of only one type of endocrine cells in the pituitary, most commonly from lactotrophs producing prolactin
Can lead to hormonal imbalances.
3
Q
What is spinal muscular atrophy?
A
Congenital degeneration of anterior horns
This condition affects motor neuron function.
4
Q
What causes amyotrophic lateral sclerosis?
A
Can be caused by a defect in superoxide dismutase 1
This is a neurodegenerative disease affecting motor neurons.
5
Q
What characterizes tabes dorsalis?
A
Degeneration/demyelination of dorsal columns and roots leading to progressive sensory ataxia
Impaired proprioception results in poor coordination.
6
Q
How does poliomyelitis spread?
A
Poliovirus infection spreads from lymphoid tissue of oropharynx to small intestine and then to CNS via bloodstream
This results in the destruction of cells in the anterior horn of the spinal cord.
7
Q
What genetic mutation is associated with Friedreich ataxia?
A
Trinucleotide repeat disorder (GAA) on chromosome 9 in the gene encoding frataxin
This leads to impairment in mitochondrial functioning.
8
Q
What is noise-induced hearing loss?
A
Damage to stereociliated cells in the organ of Corti leading to loss of high-frequency hearing
Sudden extremely loud noises can rupture the tympanic membrane.
9
Q
What is presbycusis?
A
Aging-related progressive bilateral/symmetric sensorineural hearing loss, often of higher frequencies
It involves the destruction of hair cells at the cochlear base.
10
Q
What is cholesteatoma?
A
Abnormal growth of keratinized squamous epithelium in the middle ear
Can lead to various complications, including hearing loss.
11
Q
What defines Ménière disease?
A
Increased endolymph in the inner ear leading to vertigo, hearing loss, tinnitus, and ear fullness
This condition affects balance and auditory functions.
12
Q
What is hyperopia?
A
Eye too short for refractive power of cornea and lens, causing light to focus behind the retina
This condition is also known as farsightedness.
13
Q
What is myopia?
A
Eye too long for refractive power of cornea and lens, causing light to focus in front of the retina
This condition is commonly referred to as nearsightedness.
14
Q
What is astigmatism?
A
Abnormal curvature of the cornea leading to different refractive power at different axes
It causes blurred vision at all distances.
15
Q
What is presbyopia?
A
Aging-related impaired accommodation primarily due to lens elasticity loss
It typically affects near vision.
16
Q
What is glaucoma?
A
Optic neuropathy causing progressive vision loss, usually accompanied by increased intraocular pressure
It can lead to peripheral vision loss.
17
Q
What characterizes open-angle glaucoma?
A
Associated with increased resistance to aqueous humor drainage through the trabecular meshwork
This is the most common form of glaucoma.
18
Q
What is angle-closure glaucoma?
A
Anterior chamber angle is narrowed or closed, obstructing drainage pathways by the iris
It can lead to acute eye pain and visual disturbances.
19
Q
What is diabetic retinopathy?
A
A condition caused by chronic hyperglycemia leading to permeability and occlusion of retinal vessels, resulting in microaneurysms and hemorrhages (nonproliferative) and retinal neovascularization due to chronic hypoxia (proliferative)
Diabetic retinopathy is a major cause of vision loss in individuals with diabetes.
20
Q
What mechanism leads to hypertensive retinopathy?
A
Chronic hypertension causes spasm, sclerosis, and fibrinoid necrosis of retinal vessels
Hypertensive retinopathy can lead to visual impairment and is often associated with systemic hypertension.
21
Q
What usually causes retinal artery occlusion?
A
Blockage of central or branch retinal artery usually due to embolism, commonly from carotid artery atherosclerosis or cardiogenic sources
Less commonly, it can be due to giant cell arteritis.
22
Q
What is the primary cause of retinal vein occlusion?
A
Primary thrombosis leads to central retinal vein occlusion; secondary thrombosis occurs at arteriovenous crossings due to sclerotic arteriole compressing adjacent venule, causing turbulent blood flow
This condition can result in significant visual loss.
23
Q
What is retinal detachment?
A
Separation of neurosensory retina from underlying retinal pigment epithelium, leading to loss of choroidal blood supply, hypoxia, and degeneration of photoreceptors
It can be due to retinal tears (rhegmatogenous) or tractional/exudative causes (nonrhegmatogenous).
24
Q
What characterizes retinitis pigmentosa?
A
Progressive degeneration of photoreceptors and retinal pigment epithelium
This genetic disorder leads to progressive vision loss.
25
What is papilledema?
Swelling of the optic disc usually bilateral, due to increased intracranial pressure (ICP), often secondary to mass effect
## Footnote
Impaired axoplasmic flow in the optic nerve contributes to this condition.
26
What does a relative afferent pupillary defect indicate?
Unilateral or asymmetric lesions of the afferent limb of the pupillary reflex, affecting the retina or optic nerve
## Footnote
It can signify significant optic nerve damage or retinal disease.
27
What causes Horner syndrome?
Lesions along the sympathetic chain affecting various neurons, including pontine hemorrhage or carotid dissection
## Footnote
Symptoms include ptosis, miosis, and anhidrosis.
28
What is cavernous sinus syndrome?
A condition secondary to pituitary tumor mass effect, carotid-cavernous fistula, or cavernous sinus thrombosis related to infection
## Footnote
This syndrome can lead to ophthalmoplegia and sensory deficits in the distribution of cranial nerves.
29
What typically causes delirium?
Usually secondary to illnesses such as CNS disease, infection, trauma, substance use, or medications like anticholinergics
## Footnote
Delirium is characterized by an acute change in mental status.
30
What is schizophrenia?
A mental disorder characterized by distortions in thinking, perception, emotions, language, and sense of self
## Footnote
It often includes symptoms such as delusions and hallucinations.
31
What is distal renal tubular acidosis (type 1)?
Characterized by altered dopaminergic activity and inability of a-intercalated cells to secrete H+, leading to metabolic acidosis
## Footnote
This condition results in reduced bicarbonate generation.
32
What is proximal renal tubular acidosis (type 2)?
Defective proximal convoluted tubule (PCT) bicarbonate reabsorption leads to bicarbonate excretion in urine and metabolic acidosis
## Footnote
This type is often associated with Fanconi syndrome.
33
What characterizes hyperkalemic tubular acidosis (type 4)?
Caused by hypoaldosteronism or aldosterone resistance, leading to potassium retention and impaired ammonium synthesis in the PCT
## Footnote
It results in hyperkalemia and metabolic acidosis.
34
What is nephritic syndrome?
Characterized by glomerular inflammation, GBM damage, loss of RBCs in urine, dysmorphic RBCs, and hematuria
## Footnote
It can be associated with conditions like post-streptococcal glomerulonephritis.
35
What is nephrotic syndrome?
Characterized by podocyte damage leading to impaired charge barrier and significant proteinuria
## Footnote
It may also present with edema and hyperlipidemia.
36
What is nephritic-nephrotic syndrome?
Severe GBM damage leads to both hematuria and proteinuria due to impaired charge barrier
## Footnote
This condition combines features of both nephritic and nephrotic syndromes.
37
What is Superior mesenteric artery syndrome?
Compression of transverse (third) portion of duodenum by SMA and aorta
38
What is Achalasia?
Loss of postganglionic inhibitory neurons (contain NO and VIP) in myenteric plexus → failure of LE.S relaxation
39
What is Barrett esophagus?
Replacement (metaplasia) of nonkeratinized stratified squamous epithelium with intestinal epithelium (nonciliated columnar with goblet cells)
40
What causes Acute gastritis 2° to NSAIDs?
+ PGE, → t gastric protection
41
What is Celiac disease?
Autoimmune-mediated intolerance of gliadin (found in wheat) → malabsorption (distal duodenum, proximal jejunum), steatorrhea
42
What is Fistula formation in Crohn's disease?
Transmural inflammation
43
What is Meckel diverticulum?
Persistence of the vitelline (omphalomesenteric) duct
44
What causes Hirschsprung disease?
Loss of function mutation in RET → failure of neural crest migration → lack of ganglion cells/enteric nervous plexuses in distal colon
45
What is the Adenoma-carcinoma sequence in colorectal cancer?
Loss of APC (+ intercellular adhesion, † proliferation) → KRAS mutation (unregulated intracellular signaling) → loss of tumor suppressor genes (TP53, DCC)
46
What role do Stellate cells play in cirrhosis?
Stellate cells
47
What is the mechanism of Acute cholangitis?
Biliary tree obstruction → stasis/bacterial overgrowth
48
What causes Acute pancreatitis?
Autodigestion of pancreas by pancreatic enzymes
49
What is Rh hemolytic disease of the newborn?
Rh © mother form antibodies (maternal anti-D IgG) against RBCs of Rh * fetus
50
What is the cause of Anemia in lead poisoning?
Lead inhibits ferrochelatase and ALA dehydratase → t heme synthesis, 1 RBC protoporphyrin.
51
What is Anemia of chronic disease?
Inflammation → 1 hepcidin → t release of iron from macrophages, t iron absorption from gut
52
What is G6PD deficiency?
Defect in G6PD → / NADPH → t reduced glutathione → 1 RBC susceptibility to oxidant stress
53
What causes Sickle cell anemia?
Point mutation - substitution of glutamic acid with valine in B chain → low O, high altitude, acidosis precipitates sickling (deoxygenated HbS polymerizes) → anemia, vaso-occlusive disease
54
What is Bernard-Soulier syndrome?
+ Gplb → + platelet-to-vWF adhesion
55
Fill in the blank: In Wilson disease, mutated hepatocyte copper-transporting ATPase leads to _______ incorporation into apoceruloplasmin.
t copper
56
Fill in the blank: In Hemochromatosis, HFE mutation on chromosome 6 leads to _______ intestinal absorption.
†
57
True or False: Fistula formation in Crohn's disease is characterized by transmural inflammation.
True
58
Fill in the blank: Misfolded proteins aggregate in hepatocellular ER leading to _______.
cirrhosis
59
What is the main consequence of cirrhosis?
Cirrhosis → portosystemic shunts → t NH3 metabolism
60
What is the clinical manifestation of gallstone ileus?
Fistula between gallbladder and GI tract - stone enters GI lumen - obstructing ileocecal valve (narrowest point)
61
What is the mechanism of Osteoarthritis?
Mechanical degeneration of articular cartilage causing inflammation with inadequate repair and osteophyte formation.
62
What type of hypersensitivity reaction is involved in Rheumatoid arthritis?
Autoimmune inflammation due to HLA-DR4 causing pannus formation.
63
What type of hypersensitivity is Sjogren syndrome associated with?
Type III Hypersensitivity reaction.
64
What is the mechanism of Systemic lupus erythematosus?
Autoimmune Type IV hypersensitivity reaction leading to lymphocyte mediated damage of exocrine glands.
65
What causes blindness in giant cell (temporal) arteritis?
Ophthalmic artery occlusion.
66
What autoantibodies are involved in Myasthenia gravis?
Autoantibodies to postsynaptic nicotinic (ACh) receptors.
67
What autoantibodies are associated with Lambert-Eaton myasthenic syndrome?
Autoantibodies to presynaptic calcium channels → + ACh release.
68
What is the primary defect in Albinism?
Normal melanocyte number, t melanin production.
69
What is the primary defect in Vitiligo?
Autoimmune destruction of melanocytes.
70
What factors contribute to Atopic dermatitis?
* Epidermal barrier dysfunction
* Genetic factors (ie, loss-of-function mutations in the filaggrin [FLG] gene)
* Immune dysregulation
* Altered skin microbiome
* Environmental triggers of inflammation.
71
What is the mechanism of Allergic contact dermatitis?
Type IV HSR. During the sensitization phase, Allergen activates Th1 cells - memory CD4+ cells and CD8+ form. Upon reexposure → CD4+ cells release cytokines and CD8+ cells kill targeted cells.
72
What causes Psoriasis?
Disrupted skin barrier → activation of dendritic cells via inflammatory cytokines (IL-1B, IL-6, TNF) - activated dendritic cells release IL-23 → Naive T cells form Th1 (IL-12) and Th17 (IL-23) cells that secrete IFN-y and IL-17A/IL-22 respectively → Acanthosis, parakeratosis, hypogranulosis.
73
What type of hypersensitivity is Pemphigus vulgaris associated with?
Type II HSR. IgG autoantibodies form against desmoglein 1 and 3 in desmosomes - separation of keratinocytes in stratum spinosum from stratum basale.
74
What type of hypersensitivity is Bullous pemphigoid associated with?
Type II HSR. IgG autoantibodies against hemidesmosomes - separation of epidermis from dermis.
75
What is the cause of Spina bifida occulta?
Failure of caudal neuropore to fuse by 4th week of development.
76
What causes Anencephaly?
Failure of rostral neuropore to close → no forebrain, open calvarium.
77
What is Holoprosencephaly caused by?
Failure of the forebrain (prosencephalon) to divide into 2 cerebral hemispheres; developmental field defect typically occurring at weeks 3-4 of development; associated with SHH mutations.
78
What is Lissencephaly?
Failure of neuronal migration - smooth brain surface lacking sulci and gyri.
79
What characterizes Chiari I malformation?
Downward displacement of cerebellar tonsils inferior to foramen magnum.
80
What is Chiari II malformation associated with?
Herniation of cerebellum (vermis and tonsils) and medulla through foramen magnum - noncommunicating hydrocephalus.
81
What is Dandy-Walker malformation?
Agenesis of cerebellar vermis - cystic enlargement of 4th ventricle that fills the enlarged posterior fossa; associated with noncommunicating hydrocephalus.
82
What is Glanzmann thrombasthenia?
A condition characterized by defective platelet plug formation due to impaired platelet-to-platelet aggregation
83
What causes thrombotic thrombocytopenic purpura?
Degradation of von Willebrand factor (vWF) multimers due to reduced ADAMTS13 activity, leading to microthrombi formation
84
What is von Willebrand disease associated with?
Increased platelet-to-vWF adhesion and possible prolonged activated partial thromboplastin time (aPTT) due to vWF's protective effect on factor VIII
85
What mutation is involved in Factor V Leiden?
A mutant factor V (Arg506GIn) that is resistant to degradation by protein C
86
What injury is indicated by a flattened deltoid?
Axillary nerve injury due to fractured surgical neck or anterior dislocation of the humerus
87
What are the effects of radial nerve injury?
Wrist/finger drop and decreased grip strength due to compression of the axilla or midshaft humeral fracture
88
What is the result of a proximal median nerve lesion?
Loss of sensation over the thenar eminence and the dorsal and palmar aspect of the lateral 3½ fingers
89
What happens in a distal median nerve lesion?
Carpal tunnel syndrome leading to loss of sensation and motor function in the hand
90
What is the consequence of a proximal ulnar nerve lesion?
Radial deviation of the wrist on flexion
91
What is the result of a distal ulnar nerve lesion?
Ulnar claw on digital extension
92
What is Erb's palsy?
A condition caused by traction or tear of C5-C6 roots during delivery or trauma, leading to 'waiter's tip' posture
93
What does Klumpke palsy involve?
Traction or tear of C8-T1 roots during delivery, leading to hand weakness and claw hand deformity
94
What is winged scapula caused by?
Injury to the long thoracic nerve (C5-C7), often during axillary node dissection
95
What leads to common peroneal nerve injury?
Trauma on the lateral aspect of the leg or fracture of the fibular neck, resulting in foot drop
96
What is the result of superior gluteal nerve injury?
Trendelenburg sign indicating weakness of hip abductors
97
What causes pudendal nerve injury?
Injury during horseback riding or prolonged cycling, possibly blocked during delivery
98
What is radial head subluxation also known as?
Nursemaid's elbow, caused by a sudden pull on the arm in children
99
What characterizes slipped capital femoral epiphysis?
Obese young adolescent with hip/knee pain due to displacement of the femoral head relative to the femoral neck
100
What genetic mechanism leads to achondroplasia?
Constitutive activation of FGFR3 causing failure of endochondral ossification
101
What is osteoporosis?
Decreased osteoclast activity leading to reduced bone resorption, often due to low estrogen levels and aging
102
What causes osteopetrosis?
Carbonic anhydrase II mutations leading to decreased osteoclast activity and dense bones prone to fractures
103
What is osteitis deformans also known as?
Paget's disease, characterized by abnormal bone remodeling resulting in poor quality bone
104
Fill in the blank: ____________ is characterized by defective platelet plug formation due to impaired platelet aggregation.
Glanzmann thrombasthenia
105
True or False: von Willebrand disease protects factor VIII, resulting in increased aPTT.
True
106
What is the mechanism behind Factor V Leiden?
A mutant factor V that is resistant to degradation by protein C
107
What is syringomyelia?
Fluid-filled, gliosis-lined cavity within spinal cord, associated with Chiari I malformation, less commonly with infections, tumors, trauma
## Footnote
Chiari I malformation involves low-lying cerebellar tonsils.
108
What syndrome is characterized by agraphia, acalculia, finger agnosia, and left-right disorientation?
Gerstmann syndrome
## Footnote
This syndrome results from a lesion in the dominant parietal cortex.
109
Hemispatial neglect syndrome is associated with lesions in which part of the brain?
Nondominant parietal cortex
## Footnote
This syndrome leads to neglect of one side of space.
110
What is Klüver-Bucy syndrome?
Bilateral lesions in the amygdala; seen in HSV-1 encephalitis, leading to disinhibition, including hyperphagia, hypersexuality, hyperorality
## Footnote
This syndrome affects emotional responses and behavior.
111
What is the primary cause of Parinaud syndrome?
Lesion in the dorsal midbrain, often due to pineal gland tumors
## Footnote
Parinaud syndrome includes inability to move eyes up and down.
112
What is cerebral edema?
Fluid accumulation in the brain parenchyma, which may be cytotoxic or vasogenic
## Footnote
Cytotoxic edema is associated with early ischemia, while vasogenic edema is related to increased permeability of the blood-brain barrier.
113
What causes aphasia?
Stroke in dominant hemisphere, affecting either Wernicke's area (receptive aphasia) or Broca's area (expressive aphasia)
## Footnote
Wernicke's area is located in the superior temporal gyrus, and Broca's area is in the inferior frontal gyrus.
114
What characterizes locked-in syndrome?
Loss of horizontal eye movements but not vertical eye movements
## Footnote
This condition is often caused by a stroke of the basilar artery.
115
What is lateral pontine syndrome associated with?
Stroke of the anterior inferior cerebellar artery
## Footnote
This syndrome affects the lateral aspect of the pons.
116
What is medial medullary syndrome?
Stroke of the anterior spinal artery
## Footnote
This syndrome affects the medial portion of the medulla oblongata.
117
What is neonatal intraventricular hemorrhage?
Bleeding into the ventricles in premature infants due to reduced glial fiber support and impaired autoregulation of blood pressure
## Footnote
It originates in the germinal matrix.
118
What causes an epidural hematoma?
Rupture of middle meningeal artery, often secondary to skull fracture involving the pterion
## Footnote
This type of hematoma is typically arterial and can lead to rapid deterioration.
119
What is a subdural hematoma?
Rupture of bridging veins; can be acute or chronic
## Footnote
Acute cases often result from high-energy impact, while chronic cases may follow mild trauma.
120
What is a common cause of subarachnoid hemorrhage?
Trauma, rupture of aneurysm, or arteriovenous malformation
## Footnote
This type of hemorrhage involves bleeding in the subarachnoid space.
121
What leads to intraparenchymal hemorrhage?
Systemic hypertension, amyloid angiopathy, arteriovenous malformation, or reperfusion injury in ischemic stroke
## Footnote
This type of hemorrhage occurs within the brain tissue.
122
What is phantom limb pain?
Sensation of pain in a limb that is no longer present, most commonly following amputation
## Footnote
This phenomenon is due to reorganization of the primary somatosensory cortex.
123
What causes diffuse axonal injury?
Traumatic shearing of white matter tracts during rapid acceleration and/or deceleration of the brain
## Footnote
This often results from motor vehicle accidents and can lead to coma or persistent vegetative state.
124
What is infection-associated glomerulonephritis?
A kidney condition associated with infections leading to inflammation of the glomeruli
125
What genetic mutation is associated with Alport syndrome?
Type IV collagen mutation (X-linked dominant) - irregular thinning and thickening and splitting of GBM - nephritic syndrome
126
What is stress incontinence?
Leak on increased intraabdominal pressure due to outlet incompetence (urethral hypermobility/intrinsic sphincter deficiency)
127
What causes urge incontinence?
Detrusor overactivity leading to leak with urge to void
128
What is overflow incontinence?
Leak due to incomplete emptying (detrusor underactivity or outlet obstruction) with overfilling
129
Define prerenal azotemia.
Increased renal blood flow leading to increased glomerular filtration rate and reabsorption of sodium and urea
130
What characterizes intrinsic renal failure?
Patchy necrosis causing debris obstructing tubules and fluid backflow, increasing GFR
131
What is postrenal azotemia?
Outflow obstruction (bilateral) affecting kidney function
132
What is adnexal torsion?
Twisting of ovary/fallopian tube around infundibulopelvic ligament and ovarian ligament, leading to venous/lymphatic blockage
133
What are the effects of preeclampsia?
Abnormal placental spiral arteries leading to endothelial dysfunction, vasoconstriction, ischemia, new-onset hypertension with proteinuria
134
What is supine hypotensive syndrome?
Compressed abdominal aorta and IVC by gravid uterus leading to increased placental perfusion and venous return
135
What causes functional hypothalamic amenorrhea?
Severe caloric restriction, increased energy expenditure, and/or stress altering pulsatile GnRH secretion, leading to decreased LH, FSH, estrogen
136
What is polycystic ovarian syndrome characterized by?
Hyperinsulinemia and/or insulin resistance altering hypothalamic feedback response, leading to increased LH:FSH ratio, increased androgens, and unruptured follicles (cysts)
137
What is varicocele?
Dilated veins in pampiniform plexus due to increased venous pressure, leading to enlarged scrotum
138
What is methemoglobin?
Oxidized hemoglobin secondary to dapsone, local anesthetics, or nitrites, causing decreased oxygen binding and increased cyanide affinity
139
What is deep venous thrombosis?
Blood clot within deep vein due to stasis, hypercoagulability, and endothelial damage (Virchow triad)
140
What is associated with sarcoidosis?
Noncaseating granulomas leading to increased macrophage activity and increased 1-alpha-hydroxylase activity in macrophages, resulting in vitamin D activation and increased calcium
141
Describe acute respiratory distress syndrome.
Alveolar injury causing inflammation, capillary endothelial damage, increased vessel permeability, and leakage of protein-rich fluid into alveoli
142
What causes sleep apnea?
Respiratory effort against airway obstruction or impaired respiratory effort due to CNS injury/toxicity, CHF, opioids, or obesity leading to hypoventilation
143
Fill in the blank: Type III hypersensitivity reaction is associated with _______.
consumptive hypocomplementemia
144
True or False: In prerenal azotemia, there is a decrease in renal blood flow.
False
145
What is Lesch-Nyhan syndrome caused by?
Absent HGPRT leading to de novo purine synthesis and increased uric acid production
## Footnote
HGPRT stands for hypoxanthine-guanine phosphoribosyltransferase, an enzyme involved in purine metabolism.
146
What mutation leads to B-thalassemia?
Mutation at splice site or promoter sequences resulting in retained intron in mRNA
## Footnote
This affects the production of beta-globin chains in hemoglobin.
147
What is the mechanism underlying Lynch syndrome?
Failure of mismatch repair during the S phase, leading to microsatellite instability
## Footnote
Lynch syndrome is associated with increased risk of colorectal and other cancers.
148
What defect causes I-cell disease?
N-acetylglucosaminyl-1-phosphotransferase defect leading to failure of mannose residues phosphorylation
## Footnote
This results in accumulation of cellular debris in lysosomes.
149
What is the key defect in osteogenesis imperfecta?
Type 1 collagen defect due to inability to form triple helices
## Footnote
This results in fragile bones.
150
What causes Menkes disease?
Defective ATP7A protein leading to impaired copper absorption and transport
## Footnote
This affects lysyl oxidase activity and collagen cross-linking.
151
What genetic mutation is associated with Marfan syndrome?
FBN1 mutation on chromosome 15 leading to defective fibrillin
## Footnote
Fibrillin forms a sheath around elastin in connective tissue.
152
What genetic mechanism leads to Prader-Willi syndrome?
Uniparental disomy or imprinting silencing the maternal gene
## Footnote
The disease is expressed when the paternal allele is deleted or mutated.
153
What is the genetic cause of Angelman syndrome?
Silenced gene leading to mutation or deletion of UBE3A on maternal chromosome 15
## Footnote
UBE3A is involved in protein degradation and neuronal function.
154
What mutation causes cystic fibrosis?
Autosomal recessive AF508 deletion in CFTR gene on chromosome 7
## Footnote
This leads to impaired ATP-gated Cl- channel function.
155
What is the result of dystrophin gene mutations in Duchenne muscular dystrophy?
Frameshift mutations leading to loss of anchoring protein to ECM and myonecrosis
## Footnote
Dystrophin is crucial for muscle cell integrity.
156
What genetic alteration causes myotonic dystrophy?
CTG trinucleotide repeat expansion in DMPK gene
## Footnote
This leads to abnormal expression of myotonin protein kinase causing myotonia.
157
What causes Fragile X syndrome?
Trinucleotide repeat in FMR1 gene resulting in hypermethylation
## Footnote
This leads to reduced expression of the FMR1 protein involved in neuronal development.
158
What deficiency is associated with Wernicke encephalopathy?
Thiamine deficiency leading to impaired glucose breakdown and ATP depletion
## Footnote
This condition is often seen in alcoholics.
159
What causes Pellagra in malignant carcinoid syndrome?
Tryptophan diversion towards serotonin synthesis leading to B3 deficiency
## Footnote
Vitamin B3 (niacin) is derived from tryptophan.
160
What is the result of kwashiorkor?
Protein malnutrition leading to decreased oncotic pressure and edema
## Footnote
It also results in increased apolipoprotein synthesis and liver fatty change.
161
What metabolic changes occur in alcoholism?
Increased NADH/NAD+ ratio leading to lactic acidosis, fasting hypoglycemia, and hepatic steatosis
## Footnote
Ethanol metabolism contributes to these changes.
162
What is the consequence of aspirin-induced hyperthermia?
Impaired thermoregulation leading to elevated body temperature
## Footnote
This can be a critical condition requiring medical attention.
163
What causes hereditary fructose intolerance?
Aldolase B deficiency leading to fructose-1-phosphate accumulation
## Footnote
This inhibits glycogenolysis and gluconeogenesis.
164
What is the genetic defect in classic galactosemia?
Galactose-1-phosphate uridyltransferase deficiency leading to toxic substance accumulation
## Footnote
This includes galactitol, which can accumulate in the eyes.
165
What are the ocular complications associated with diabetes mellitus?
Cataracts, retinopathy, peripheral neuropathy
## Footnote
These complications arise due to metabolic changes in the lens, retina, and Schwann cells.
166
What is recurrent Neisseria bacteremia associated with?
Terminal complement deficiencies (CS-C9)
## Footnote
This leads to failure of membrane attack complex (MAC) formation.
167
What causes hereditary angioedema?
Cl esterase inhibitor deficiency
## Footnote
This leads to unregulated activation of kallikrein, resulting in increased bradykinin.
168
What is the genetic mutation involved in paroxysmal nocturnal hemoglobinuria?
PIGA gene mutation
## Footnote
This mutation affects GPI anchors for complement inhibitors, leading to complement-mediated intravascular hemolysis.
169
What is the mechanism of type I hypersensitivity?
Immediate: antigen cross-links IgE on mast cells, causing degranulation
## Footnote
Late phase involves mast cells secreting chemokines and leukotrienes, leading to inflammation.
170
What characterizes type II hypersensitivity?
Antibodies bind to cell-surface antigens, causing cellular destruction
## Footnote
This can lead to inflammation and cellular dysfunction.
171
What is the mechanism behind type III hypersensitivity?
Antigen-antibody complexes activate complement, attracting neutrophils
## Footnote
This results in inflammation and tissue damage.
172
What defines type IV hypersensitivity?
T cell-mediated response without antibodies
## Footnote
CD8+ T cells directly kill target cells, while CD4+ T cells release cytokines.
173
What is the cause of acute hemolytic transfusion reaction?
Type II hypersensitivity reaction against donor RBCs
## Footnote
This is usually due to ABO antigen mismatch.
174
What genetic defect is associated with X-linked (Bruton) agammaglobulinemia?
Defect in BTK gene (tyrosine kinase)
## Footnote
This leads to no B-cell maturation and absent B cells in peripheral blood.
175
What is the chromosomal abnormality in DiGeorge syndrome?
22q11 microdeletion
## Footnote
This results in the failure to develop the 3rd and 4th branchial (pharyngeal) pouches.
176
What causes hyper-IgM syndrome?
Defective CD40L on Th cells
## Footnote
This leads to a class switching defect in B cells.
177
What is the defect in leukocyte adhesion deficiency (type 1)?
LFA-1 integrin (CD18) defect
## Footnote
This results in impaired phagocyte migration and chemotaxis.
178
What mutation is seen in Chédiak-Higashi syndrome?
LYST mutation
## Footnote
This causes microtubule dysfunction and a phagosome-lysosome fusion defect.
179
What is the defect in chronic granulomatous disease (CGD)?
NADPH oxidase defect
## Footnote
This leads to an inability to produce reactive oxygen species (ROS) during the respiratory burst in neutrophils.
180
What is the mechanism behind graft-versus-host disease?
Type IV hypersensitivity; HLA mismatch
## Footnote
Donor T cells attack host cells.
181
What organisms are associated with recurrent infections in CGD?
S aureus, Serratia, B cepacia
## Footnote
These are catalase-positive organisms that can survive in the absence of reactive oxygen species.
182
What condition is characterized by the presence of Shiga/Shiga-like toxins?
Hemolytic uremic syndrome
## Footnote
These toxins inactivate the 60S ribosome, leading to cytokine release.
183
What is the mechanism of action of tetanospasmin?
Prevents release of inhibitory neurotransmitters (GABA and glycine)
## Footnote
This occurs from Renshaw cells in the spinal cord.
184
What does the botulinum toxin cleave to inhibit neurotransmitter release?
SNARE proteins
## Footnote
This prevents acetylcholine release at the neuromuscular junction.
185
What is the action of the alpha toxin in gas gangrene?
Degrades phospholipids, leading to myonecrosis
## Footnote
It acts as a phospholipase/lecithinase.
186
What is the mechanism of toxic shock syndrome and scarlet fever toxins?
Cross-link B region of TCR to MHC class II on APCs
## Footnote
This leads to massive cytokine release, including IL-1, IL-2, IFN-γ, and TNF-α.
187
What is a thoracic aortic aneurysm?
A localized dilation of the thoracic aorta.
188
What is a myocardial infarction?
The interruption of blood supply to a part of the heart, causing heart tissue damage.
189
What characterizes a non-ST-segment elevation MI?
Partial thickness damage to the heart muscle without ST-segment elevation on ECG.
190
What characterizes a ST-segment elevation MI?
Full thickness damage to the heart muscle with ST-segment elevation on ECG.
191
What is the significance of death within 0-24 hours post MI?
It indicates immediate complications such as arrhythmias or cardiac rupture.
192
What does death or shock within 3-14 days post MI indicate?
It suggests complications like heart failure or ventricular rupture.
193
What is Wolff-Parkinson-White syndrome?
A condition caused by an abnormal accessory pathway that can lead to tachycardia.
194
What is hypertrophic obstructive cardiomyopathy?
A condition characterized by abnormal thickening of the heart muscle, leading to obstruction.
195
What symptoms are associated with hypertrophic obstructive cardiomyopathy?
Syncope and dyspnea.
196
What is hypovolemic shock?
Shock resulting from significant fluid loss.
197
What is cardiogenic shock?
Shock caused by the heart's inability to pump blood effectively.
198
What is distributive shock?
Shock caused by widespread vasodilation leading to inadequate blood flow.
199
What is rheumatic fever?
An inflammatory disease that can develop after a streptococcal infection.
200
What is the most common form of congenital adrenal hyperplasia?
21-hydroxylase deficiency.
201
What are common symptoms of hyperthyroidism?
Heat intolerance and weight loss.
202
What is myxedema?
A severe form of hypothyroidism characterized by swelling and skin changes.
203
What is Graves ophthalmopathy?
An autoimmune condition associated with hyperthyroidism, causing eye changes.
204
What is primary hyperparathyroidism?
A condition characterized by excessive secretion of parathyroid hormone (PTH).
205
What is secondary hyperparathyroidism?
Increased PTH due to chronic low calcium levels.
206
What is euvolemic hyponatremia in SIADH?
Low sodium levels in the blood with normal blood volume.
207
What are the two types of vessel disease in diabetes mellitus?
Small vessel disease and large vessel disease.
208
What is diabetic ketoacidosis?
A serious complication of diabetes characterized by high levels of ketones.
209
What is hyperosmolar hyperglycemic state?
A life-threatening condition with extremely high blood sugar and dehydration.
210
What is Zollinger-Ellison syndrome?
A gastrin-secreting tumor causing recurrent ulcers.
211
What is duodenal atresia?
A congenital condition where the duodenum is closed or absent.
212
What is jejunal/ileal atresia?
A congenital defect where sections of the jejunum or ileum are absent.
213
What is cystic medial degeneration?
A degenerative process affecting the media layer of the aorta.
214
What is the mechanism of myocardial infarction related to coronary artery plaque?
Rupture of coronary artery atherosclerotic plaque leading to acute thrombosis.
215
What are subendocardial infarcts?
Infarcts occurring in the subendocardium, which is vulnerable to ischemia.
216
What are transmural infarcts?
Full thickness infarcts affecting the entire wall of the heart.
217
What is the primary risk associated with ventricular arrhythmia?
Potential fatality due to disrupted heart rhythm.
218
What causes macrophage-mediated ruptures in post-MI complications?
Ruptures of the papillary muscle, interventricular septum, and free wall at specific time intervals.
219
What is the role of abnormal accessory pathways in Wolff-Parkinson-White syndrome?
They bypass the AV node, leading to early ventricular depolarization and delta waves.
220
What are the genetic mutations associated with hypertrophic obstructive cardiomyopathy?
Mutations in sarcomeric proteins like myosin binding protein C and ß-myosin heavy chain.
221
What is the effect of preload on cardiac output?
+ preload → + cardiac output.
222
What is the relationship between left heart dysfunction and cardiac output?
+ cardiac output due to left heart dysfunction.
223
What does increased systemic vascular resistance (SVR) indicate?
+ SVR indicates increased afterload.
224
What leads to the excess secretion of PTH in primary hyperparathyroidism?
Parathyroid adenoma or hyperplasia.
225
What is the consequence of 21-hydroxylase deficiency?
Deficiency in mineralocorticoids, excess cortisol, and decreased sex hormones.
226
What is the effect of Na*-K+ ATPase on basal metabolic rate?
Increased Na*-K+ ATPase leads to increased basal metabolic rate.
227
What is the result of lymphocytic infiltration in muscle tissue?
Increased osmotic muscle swelling and inflammation.
228
What is the effect of elevated PTH and ALP in primary hyperparathyroidism?
Elevated calcium levels and/or decreased phosphate levels.
229
What happens to ADH levels in SIADH?
Increased ADH leads to water retention.
230
What is the consequence of nonenzymatic glycation of proteins in diabetes?
It leads to various complications associated with diabetes.
231
What is the relationship between insulin and fat breakdown in diabetes?
Increased insulin or decreased insulin requirement leads to decreased fat breakdown.
232
What is the effect of hyperglycemia on serum osmolality?
Hyperglycemia increases serum osmolality and causes excessive osmotic diuresis.
233
What causes Zollinger-Ellison syndrome?
A gastrin-secreting tumor (gastrinoma) causing recurrent ulcers.
234
What is the consequence of failure to recanalize during fetal development?
It leads to atresia of the intestines.
235
What is the result of disruption of the SMA in fetal development?
It causes ischemic necrosis of the fetal intestine.
236
What activates macrophages in the mechanism of shock and DIC by gram-negative bacteria?
Lipid A of LPS via TLR4/CD14
## Footnote
This activation leads to complement activation and tissue factor activation.
237
What type of infection is associated with biofilm production by Staphylococcus epidermidis?
Prosthetic device infection
## Footnote
Biofilms help bacteria adhere to surfaces, making infections difficult to treat.
238
What is the primary cause of endocarditis associated with Streptococcus sanguinis?
Dextrans production binding to fibrin-platelet aggregates
## Footnote
This occurs on damaged heart valves.
239
What toxins are responsible for the watery diarrhea in pseudomembranous colitis?
Toxins A and B from Clostridium difficile
## Footnote
These toxins damage enterocytes.
240
What is the virulence factor of Mycobacterium tuberculosis that promotes granuloma formation?
Cord factor
## Footnote
It activates macrophages and induces TNF-α release.
241
What type of leprosy is characterized by a mild immune response?
Tuberculoid leprosy
## Footnote
This form is associated with a strong T-cell response.
242
What type of infections are caused by Escherichia coli?
* Cystitis
* Pyelonephritis
* Pneumonia
* Neonatal meningitis
## Footnote
These infections highlight the versatility of E. coli as a pathogen.
243
What is the mechanism of Chlamydiae resistance to antibiotics?
Resistance to β-lactam antibiotics
## Footnote
Chlamydiae lack a classic peptidoglycan structure.
244
What are the two types of influenza outbreaks?
* Pandemics
* Epidemics
## Footnote
These outbreaks differ in scale and impact on public health.
245
How does rabies virus invade the CNS?
By binding to ACh receptors and retrograde transport via dynein
## Footnote
This allows the virus to travel along nerve fibers to the CNS.
246
What is the role of macrophages in granuloma formation?
Present antigens to CD4+ T cells and secrete IL-12
## Footnote
This leads to differentiation into Th1 cells, which secrete IFN-γ for macrophage activation.
247
What phenomenon allows cancer cells to maintain limitless replicative potential?
Reactivation of telomerase
## Footnote
This prevents chromosome shortening and cellular aging.
248
What is the effect of E-cadherin on cancer cell behavior?
Maintains intercellular junctions
## Footnote
Its function is related to basement membrane and ECM degradation by metalloproteinases.
249
What congenital heart defect is characterized by failure of aorticopulmonary septum formation?
Persistent truncus arteriosus
## Footnote
This defect leads to mixed arterial and venous blood flow.
250
What is a common clinical presentation of tetralogy of Fallot?
Tet spells
## Footnote
These episodes occur due to right ventricular outflow obstruction.
251
What is Eisenmenger syndrome a consequence of?
Uncorrected left-to-right shunt leading to pulmonary hypertension
## Footnote
This can eventually cause right-to-left shunting and cyanosis.
252
What is the initial step in the pathogenesis of atherosclerosis?
Endothelial cell dysfunction
## Footnote
This leads to macrophage and LDL accumulation.
253
What sequence describes the progression of atherosclerosis?
* Foam cell formation
* Fatty streaks
* Smooth muscle cell migration
* Extracellular matrix deposition
* Fibrous plaque
* Complex atheromas
## Footnote
Each step contributes to the worsening of the condition.
254
What is conduction aphasia?
Damage to the arcuate fasciculus
255
What characterizes global aphasia?
Damage to both Broca and Wernicke areas
256
What is heat stroke?
Inability of body to dissipate heat (eg, exertion) → CNS dysfunction, rhabdomyolysis, acute kidney injury, ARDS, DIC
257
What are common triggers for migraines?
Irritation of CN V, meninges, or blood vessels (release of vasoactive neuropeptides like substance P, calcitonin gene-related peptide)
258
What is the primary mechanism of Parkinson disease?
Loss of dopaminergic neurons of substantia nigra pars compacta
259
What genetic abnormality is associated with Huntington disease?
Trinucleotide (CAG) repeat expansion in huntingtin (HTT) gene on chromosome 4
260
What pathological changes occur in Alzheimer's disease?
Widespread cortical atrophy, senile plaques composed of beta-amyloid, neurofibrillary tangles of hyperphosphorylated tau protein
261
What is the mechanism behind frontotemporal dementia?
Frontotemporal lobe degeneration affecting executive function and behavioral inhibition
262
What causes vascular dementia?
Multiple arterial infarcts and/or chronic ischemia
263
What leads to HIV-associated dementia?
Secondary to diffuse gray matter and subcortical atrophy
264
What is idiopathic intracranial hypertension?
Increased ICP, associated with dural venous sinus stenosis; impaired optic nerve axoplasmic flow → papilledema
265
What causes communicating hydrocephalus?
Reduced CSF absorption by arachnoid granulations (eg, arachnoid scarring post-meningitis) → increased ICP, papilledema, herniation
266
What characterizes normal pressure hydrocephalus?
Idiopathic, CSF pressure elevated only episodically, no increase in subarachnoid space volume; expansion of ventricles distorts the corona radiata
267
What is noncommunicating hydrocephalus?
Structural blockage of CSF circulation within ventricular system (eg, stenosis of aqueduct of Sylvius)
268
What is ex vacuo ventriculomegaly?
Decreased brain tissue and neuronal atrophy - appearance of increased CSF on imaging
269
What is osmotic demyelination syndrome?
Rapid osmotic changes, most commonly iatrogenic correction of hyponatremia, leading to massive axonal demyelination in pontine white matter
270
What is acute inflammatory demyelinating polyneuropathy?
Autoimmune destruction of Schwann cells via inflammation and demyelination of motor and sensory fibers and peripheral nerves
271
What causes Charcot-Marie-Tooth disease?
Defective production of proteins involved in the structure and function of peripheral nerves or the myelin sheath
272
What is progressive multifocal leukoencephalopathy?
Destruction of oligodendrocytes secondary to reactivation of latent JC virus infection → demyelination of CNS
