Auditory and Olfactory Systems Quiz

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is the primary role of the ossicles in the auditory system?

To provide structural support to the tympanic membrane

To modulate and amplify sound vibrations (correct)

To transduce auditory signals into neural impulses

To capture sound waves from the environment

Which structure in the inner ear is primarily responsible for sound perception?

Cochlea (correct)

Semicircular canals

Vestibular apparatus

Tympanic membrane

How do hair cells in the cochlea respond to sound stimuli?

By generating electrical impulses in response to fluid movement (correct)

By producing acoustic vibrations that enhance sound clarity

By directly converting sound waves into light signals

By transmitting signals to the cochlear duct for amplification

Which component of the auditory system is primarily involved in the localization of sound?

Pinna Signup and view all the answers

What function do the semicircular canals serve in the vestibular system?

Detecting rotational acceleration Signup and view all the answers

What is the main function of olfactory sensory neurons?

Transducing signals of odorants into receptor potentials Signup and view all the answers

Which of the following structures form the olfactory nerve?

Axons of olfactory sensory neurons Signup and view all the answers

How often are olfactory sensory neurons typically replaced?

Every 1–2 months Signup and view all the answers

What role do odorant-binding proteins play in the olfactory epithelium?

They enhance the diffusion of odorants to the odorant receptors. Signup and view all the answers

Which type of cells do olfactory sensory neurons' axons synapse with in the olfactory bulb?

Tufted and mitral cells Signup and view all the answers

What type of receptor are olfactory receptors categorized as?

G-protein-coupled receptors (GPCRs) Signup and view all the answers

What structure creates a map in the olfactory bulb for differentiating odors?

Olfactory glomeruli Signup and view all the answers

What typically happens in the signal transduction cascade initiated by odorant receptors?

Opening of Cl- and Ca+2 channels Signup and view all the answers

What is the main function of the ossicular chain in the middle ear?

To amplify movements of the eardrum Signup and view all the answers

How does the surface area of the tympanic membrane compare to that of the oval window?

The tympanic membrane is 20 times larger Signup and view all the answers

What do the stapedius and tensor tympani muscles modify?

The lever function of the ossicular chain Signup and view all the answers

What is the unique property of endolymph compared to perilymph?

High K+ concentration Signup and view all the answers

What is the role of Reissner’s membrane in the cochlea?

To separate scala vestibuli from scala media Signup and view all the answers

How many rows of hair cells are present in the organ of Corti?

Four rows total with one inner and three outer Signup and view all the answers

What is the cochlea primarily responsible for?

Transducing sound vibrations into action potentials Signup and view all the answers

What would likely happen if the ossicular chain did not function properly?

Vibrations would not be transmitted effectively to the inner ear Signup and view all the answers

Which fluid fills the scala tympani?

Perilymph Signup and view all the answers

What is the approximate length of the cochlea?

35 mm Signup and view all the answers

What type of hemolysis is more common in cold autoimmune hemolytic anemia (AIHA)?

Intravascular hemolysis Signup and view all the answers

Which of the following is characteristic of warm AIHA?

Massive hemolysis and life-threatening anemia Signup and view all the answers

What does a Direct Coomb's test primarily evaluate?

Antibodies bound to the patient’s RBCs Signup and view all the answers

What is the function of the Indirect Coomb’s test?

To expose the patient’s plasma to standard RBCs Signup and view all the answers

Which component is NOT included in a complete blood count (CBC)?

Serum electrolytes Signup and view all the answers

Which of the following symptoms is more likely to occur in warm AIHA compared to cold AIHA?

Rapid development of jaundice Signup and view all the answers

What aspect does the RBC distribution width (RDW) measure in a CBC?

Variability in the size of red blood cells Signup and view all the answers

What is the primary result of complement activation in cold AIHA?

Intravascular hemolysis of red blood cells Signup and view all the answers

What is the most common cause of sensorineural hearing loss?

Presbycusis Signup and view all the answers

Which condition is NOT associated with conductive hearing loss?

Meniere’s disease Signup and view all the answers

What frequency range is the human ear best at hearing?

1000 - 4000 Hz Signup and view all the answers

What effect does a tympanic membrane perforation typically have on hearing?

Causes conductive hearing loss Signup and view all the answers

Which statement is true regarding the tuning fork tests for hearing?

Normal hearing shows equal sensitivity in both Weber and Rinne tests. Signup and view all the answers

What is the major risk factor for developing presbycusis?

Age-related neuronal loss Signup and view all the answers

Which of the following agents is commonly known to be ototoxic?

Antibiotics Signup and view all the answers

What type of hearing loss is primarily impacted by the transmission of sound in the outer and middle ear?

Conductive hearing loss Signup and view all the answers

Which condition is characterized by the presence of a cystic lesion in the middle ear?

Cholesteatoma Signup and view all the answers

What is the most common complication associated with cholesteatoma?

Conductive hearing loss Signup and view all the answers

Which of the following is a characteristic of primary acquired cholesteatoma?

Most cases are due to chronic inflammation Signup and view all the answers

What is a hallmark finding in cholesteatoma patients?

Painless otorrhea Signup and view all the answers

How does the pathogenesis of primary acquired cholesteatoma generally progress?

Migration of respiratory epithelium due to inflammation Signup and view all the answers

What contributes to the growth of the cystic structure in cholesteatoma?

Accumulation of keratinized cells Signup and view all the answers

Which area of the tympanic membrane is most likely involved in primary acquired cholesteatoma?

Pars flaccida Signup and view all the answers

Which secondary acquired cause is less common compared to primary acquired cholesteatoma?

Surgical insertion of ear tubes Signup and view all the answers

What is a potential serious consequence of untreated cholesteatoma?

Intracranial infection Signup and view all the answers

Which type of cholesteatoma is most commonly associated with a history of head trauma?

Secondary acquired cholesteatoma Signup and view all the answers

Which possible post-operative outcome is common after cholesteatoma surgery?

Some degree of hearing loss Signup and view all the answers

Study Notes

BMS 200 - Physiology of Hearing, Taste, and Olfaction

The course covers the physiology of taste receptors and taste perception, olfaction, the anatomy and physiology of the middle and external ears, auditory stimulus transmission and modulation, the relationship between ECM components and middle ear structures, the organs of hearing and equilibrium (including the external, middle, and inner ear, and the vestibular system), functions of auditory system components, the physiological processes involved in sound transmission, the intricate mechanisms of the cochlea, and the function of the inner ear in sound perception, the relationship between semicircular canals and otolith organs and their functions in detecting rotational and linear acceleration.

Outcomes for Today

Physiology of taste receptors, taste perception, and olfaction will be described.
The anatomy and physiology of the middle and external ears, including structures for auditory stimulus transmission and modulation, will be covered.
The relationship between extracellular matrix (ECM) components and middle ear structures, including ossicles and the tympanic membrane, in sound conduction will be discussed.
Anatomical structures of hearing and equilibrium organs (external, middle, and inner ear, and vestibular system) will be detailed.

Outcomes for Today (cont.)

Functions of auditory system components (pinna, external auditory canal, tympanic membrane, ossicles, cochlea, and vestibular apparatus) will be described.
Physiological processes in sound transmission (from external ear to inner ear transduction and amplification) will be discussed.
Mechanisms in the cochlea including the arrangement of hair cells, role of basilar membrane, and cochlear duct function in sound perception.
Relationship between semicircular canals and otolith organs' function in detecting rotational and linear acceleration will be addressed.

The Ear - General Structure

Diagrams of the outer, middle, and inner ear are shown.
The structures such as Helix, Auricle, External auditory meatus, Earlobe, tympanic membrane, auditory ossicles, Semicircular canals, Facial nerve, Vestibular nerve, Cochlear nerve, Cochlea, Temporal bone, Round window, and Auditory tube are labeled.

Outer Ear - Structures

The auricle (pinna) is described, composed of helix, lobule, and tragus.
Functions of the outer ear include focusing sound waves onto the tympanic membrane and modifying sound from different directions based on its structure.
The auditory meatus (ear canal) contains ceruminous glands that produce cerumen (earwax), which traps foreign substances and protects the canal.
Cerumen is composed of anti-microbial proteins, saturated fatty acids, and sloughed keratinocytes.

Middle Ear - Structures

The tympanic membrane separates the outer and middle ear. It's a fibroelastic connective tissue with simple cuboidal epithelium lining.
The tympanic cavity contains the auditory ossicles (malleus, incus, and stapes) that conduct sound vibrations.
The auditory tube (Eustachian tube) connects to the nasopharynx, equalizing pressure between the middle ear and the atmosphere during swallowing or yawning.

Middle Ear - Structures (cont.)

The malleus (hammer) is attached to the eardrum and incus, a synovial joint.
The incus (anvil) is linked to the malleus and stapes.
The stapes (stirrup) connects to the oval window, a transition point to the inner ear.

Middle Ear - Key Structures

Diagram of major structures including the temporal bone, epitympanic recess, tensor tympani muscle, stapedius muscle, ossicles, tympanic membrane, tympanic cavity, and the eustachian tube are noted.

If you were building an ear at Home Depot

The middle ear is a lever system amplifying eardrum vibrations (of the tympanic membrane) to the oval window of the scala vestibuli.
The stapedius and tensor tympani muscles modify this lever system tuning response of the system based on frequency and intensity of sound.

Middle Ear - Structures (cont. 2)

The purpose of the middle ear bones is to act as levers, amplifying vibrations from the tympanic membrane to the oval window.
This lever system and surface area differences overcome the air-to-water acoustic impedance challenge.

Inner Ear - Structures for Sound

The cochlea (snail-like structure) is coiled and contains about 1,000,000 moving parts (stereocilia) for sound transformation.
The cochlea connects to the oval window (filled with perilymph), separated from the middle, by Reissner's membrane.
The scala tympani connects to the round window filled with perilymph, separated from the middle by the basilar membrane.

Inner Ear - Structures for Sound (cont. 2)

The scala media (middle chamber) houses inner and outer hair cells containing endolymph in a different ionic composition from perilymph.
The basilar membrane holds inner and outer hair cells that contact the tectorial membrane.
Inner hair cells are a single row with about 3500 cells; outer hair cells come in three rows and have around 16,000 cells.
Both inner and outer hair cells project into the endolymph.

Inner Ear - Structures for Sound (cont. 3)

Endolymph has a high K+ concentration (around 80 mmol/L); perilymph has composition similar to cerebrospinal fluid (CSF) but has low protein values.
The stria vascularis in the scala media secretes K+ into the scala media, creating a massive K+ gradient between the endolymph and perilymph.

The Process of Hearing - Step-by-Step

Sound waves are transmitted from the outer ear to the middle ear (tympanic membrane to the ossicles to the oval window).
The oval window's movement causes vibrations in the basilar membrane, activating hair cells in the organ of Corti.
The basilar membrane bends and shears against the tectorial membrane.
Outer hair cells move, modifying basilar membrane motion.

The Process of Hearing - Step-by-Step (cont.)

Inner hair cells (IHCs) are activated by basilar membrane movement, resulting in neurotransmitter release.
Neurotransmitter signals travel to different parts of the auditory cortex.
The resulting sound's frequency is distinguished by the basilar membrane's point of maximum vibration (with higher frequencies towards the oval window and lower towards the helicotrema).

The Process of Hearing - Details

High-frequency sounds are detected closer to the oval window, while low-frequency sounds are detected closer to the helicotrema.
Pitch is identified based on the specific part of the organ of Corti that detects the sound.
Loudness differences result from the degree of basilar membrane vibration.

What is Sound?

Sound waves are generated by the compression and rarefaction of molecules in the surrounding medium.

Equilibrium and the Vestibular Apparatus

Detects equilibrium through two types: static (head position, no movement) and dynamic (angular movement of head).
Static equilibrium senses head orientation relative to gravity, responding to changes.
Dynamic equilibrium senses rotational and angular movement of the head, with respect to the semicircular canals, and the utricle/saccule reacting to movements and the position of the head.

The Vestibular System

The vestibular system, residing within the inner ear, contains semicircular canals, utricle, and saccule.
The semicircular canals detect rotational movements while the utricle and saccule sense head position and linear acceleration.
They perform coordinated functions involving push-pull responses, one canal stimulating an opposite canal.

Vestibular Apparatus

The labyrinth (inner part of the inner ear) has semicircular canals sensing rotary movement, and the utricle/saccule sensing linear acceleration and static head position.

Utricle and the Saccule

The utricle and saccule are otolithic organs that sense static equilibrium and linear accelerations and decelerations.
They have otoliths on the hair cells which allow them to detect movements and positional changes in the head.

Utricle and the Saccule (cont.)

The otolithic membrane deflects the hair cell stereocilia in response to movement, generating a message of equilibrium and position.
The utricle is horizontally oriented and the saccule is vertically oriented.

Smell and Taste

Chemoreceptors dedicated to taste and smell are activated by chemicals in saliva (tastants) and mucus (odorants).
The taste tongue has approximately 5000 taste buds in papillae along its dorsum and sides. Four main types of papilla: fungiform, circumvallate, foliate, and filiform.

Taste Buds

Fungiform papillae typically harbor up to 5 taste buds, primarily at their apex.
Circumvallate papillae can contain up to 100 taste buds, mainly along the papilla's sides.
Filiform papillae lack taste buds but contribute to the tongue's texture.

Taste Buds (cont.)

Taste buds, beyond the tongue, are also present in the soft palate, epiglottis, and pharynx.
Each taste bud has 50-100 taste receptor cells which exhibit microvilli at the apex, studded with receptors for tastants.
These microvilli project into a taste pore.

Taste

Saliva dissolves tastants, allowing for taste reception.
Taste buds are innervated by 50 nerve fibers, each receiving input from an average of 5 taste buds, with a 10-day lifespan for taste cells.
Humans have five fundamental taste modalities, including salt, sweet, sour, bitter, and umami, recognized by different gustatory axons.

Taste Perception

Salt taste is perceived by activation of epithelial sodium channels, resulting in membrane depolarization.
Sour taste is triggered by proton stimulation (H+), which may block K+-sensitive channels through ENaCs, causing membrane depolarization.
Sour transduction might involve hyperpolarization-activated cyclic nucleotide-gated cation channels (HCN).

Taste Perception (cont.)

Sweet perception involves at least two G protein-coupled receptors (GPCRs)—T1R2 and T1R3—activated by natural sugars and structurally different compounds.
Bitter taste arises from a variety of unrelated compounds acting as potential warning signals.
Some bitter compounds block K+ channels; others bind to GPCRs (T2R). Umami perception is mediated by T1R3 and metabotropic glutamate, a naturally occurring protein.

Structure of the Olfactory Epithelium

Specialized part of nasal mucosa in the upper nasal cavity near the septum (approximately 10 cm2). 
Major cell types include olfactory sensory neurons (bipolar neurons crucial in odorant signal transduction), and supporting cells responsible for secreting mucus for optimal detection.

Structure of the Olfactory Epithelium (cont.)

Olfactory sensory neurons' axons traverse the cribriform plate to reach the olfactory bulbs.
Supporting cells in the epithelium secrete mucus, optimizing chemical detection around cilia.
Odorant-binding proteins in mucus enhance odorant diffusion to and from receptors.
Olfactory neurons are routinely replaced by basal stem cells.

Odorant Receptors and Signal Transduction

Odorant receptors vary significantly in amino acid sequence, all being G-protein coupled receptors (GPCRs).
Typical G protein (Gs) is involved in Cl- and Ca+2 channels, signaling process.

Olfactory Sensory Pathway Overview

Olfactory sensory neurons’ axons synapse on mitral or tufted cells, forming glomeruli (olfactory bulb).
Each olfactory neuron expresses only one of the 400 functional olfactory genes, a one-to-one mapping.
Mitral cells and their glomeruli project odorants to regions in the olfactory cortex.

Otosclerosis

Bone deposition, often around the oval window area of the middle ear.
Familial (autosomal dominant) and may be related to measles infection.
The pathogenesis involves an imbalance between bone deposition and resorption.
Clinical features include progressive hearing loss due to immobilization of the oval window.

Otitis Externa

Bacteria (staph, pseudomonas, E. coli) usually cause it.  
Risk factors include: humidity, loss of cerumen, heat, increased pH, ear canal obstruction, and environmental exposures.  
The ear's secretions are acidic, acting as a barrier to infection. Water (with colonization by bugs) in the ear canal increases risk of infection.  
Manifestations include pain, purulent otorrhea, itching, edema, and possibly conductive hearing loss.

Otitis Media

Mostly viral infections in children.
Pathogens invade via the external auditory, causing edema, fibrosis, perforation, and persistent infection.  
Acute otitis media (AOM) is characterized by a rapid onset of fever, otalgia, and conductive hearing loss and often resolves with or without intervention.

Otitis Media (cont.)

Chronic otitis media is when infections are ongoing and persistent; it’s typically associated with Eustachian tube dysfunction and/or perforation. 
Chronic otitis media can have several types, such as suppurative, serous, or benign (“dry”) chronic types, which are distinguished by their characteristics.

Otitis Externa, Variations

Furunculosis is an otitis externa usually of staphylococcal nature in the external part of ear canal.   
Chronic otitis externa involves less painful or more itchy infections, often due to repetitive trauma or ongoing middle ear infections.  
Malignant or necrotizing otitis externa is a severe possibility, potentially life-threatening, requiring early and aggressive intervention.
Otomycosis, a form of fungal infection within the external auditory canal, involves species like Aspergillus and Candida.

Cholesteatomas

Benign cyst-like lesions found in the middle ear, not a neoplasm but contain keratin, cellular debris.  
Cholesteatoma types include congenital (rare, primary) occurring from birth or secondary (acquired), often due to damage to the tympanic membrane or repeated infections. 
Cholesteatomas can cause significant hearing loss, possibly involving facial nerve palsy or intracranial complications such as meningitis.

Cholesteatoma - Complications

Can cause conductive hearing loss, even after surgical intervention to remove the cholesteatoma.  
Bony destruction and intracranial complications, such as infections and meningitis are serious possible consequences of cholesteatoma, especially if it becomes infected or ruptures into other areas. 
Removal of the lesions is usually a treatment strategy intended to avoid further damage and prevent severe complications.

Cholesteatoma - Pathogenesis

Secondary acquired cholesteatomas (more common) often follow traumatic implantation of keratinized epithelial cells from the outer ear side, or damage to the inner canal, often through an injury, or surgical procedure. Often inflammation and abnormal TM cell migration are factors in its development.
Primary acquired cholesteatomas involve improper placement of keratinized epithelial cells and often are related to chronic inflammation, usually developing in teenagers to adults.

Primary Acquired Cholesteatoma - Pathogenesis (cont.)

Mucous accumulation in the pouch, with chronic inflammation and infection, often from pseudomonas.
This is followed by implantation/conversion of some cells in the cyst to keratinized epithelial cells, with the outer surface of the tympanic membrane being incorporated into the cyst structure.
The “stuck” keratinized cells keep dividing and inflammation growth of the cystic structure.

Primary Acquired Cholesteatoma - Appearance on Otoscopy

Normal ear otoscopy shows structures like pars flaccida, incus, pars tensa, and normal positioning of the malleus in the eardrum.
Small or huge cholesteatoma is seen as a noticeable mass.

Cholesteatomas

Not a common disorder (around 10 per 100,000/year).  
Hallmark findings are painless otorrhea worsening with infection and sometimes sensorineural or conductive hearing loss. 
Usually discovered and surgically treated; complications include substantial hearing loss.

Cholesteatoma (cont.)

Other clinical features include vertigo or dysequilibrium from inflammatory processes in the middle ear or labyrinth.
Facial nerve palsy may also result from associated inflammation or mechanical nerve compression, especially when large.

Dizziness

Dizziness is classified as: vertiginous (environment seems to move, typically due to inner ear or brainstem/cerebellar systems) and non-vertiginous (not due to inner ear, but possible issues with blood pressure or brain function).

Benign Paroxysmal Positional Vertigo (BPPV)

Acute attacks of transient rotatory vertigo lasting seconds to minutes, often initiated by certain head positions and accompanied by rotatory nystagmus.
Often caused by a free-floating otolith that gets dislodged during head movement, causing abnormal activation of vestibular receptors.

BPPV (cont.)

Diagnosis is made through Dix-Hallpike positional testing, where rapid head movements from a seated to supine position, with the head turned to one side and the neck extended for ~20 seconds, initiate the onset of vertigo.

Meniere's Disease

Episodic attacks of tinnitus, hearing loss, vertigo lasting minutes to hours
Characterized by inadequate endolymph absorption, endolymphatic over-accumulation, and distortion of the membranous labyrinth.   
Typically manifests in middle-aged individuals and can be triggered by high salt intake, caffeine, stress, nicotine, and alcohol.  Three diagnostic criteria include at least two spontaneous episodes of at least 20 minutes in duration vertigo, an audiometry showing evidence of sensorineural hearing loss, and tinnitus or a feeling of fullness in the ear.

Vestibular Neuronitis

Sudden onset of disabling vertigo, often accompanied by nausea, vomiting, and imbalance, most likely due to URTI.
Typically lasts 1-5 days in terms of acute phase and usually accompanied by nystagmus which causes the patient’s eyes to move toward the affected side.
Convalescent phase often involves imbalance and motion sickness lasting days to weeks, and gradual vestibular adaptation to recover over weeks to months.

Labyrinthitis

Acute infection of inner ear, caused by a virus or bacteria. 
Patients often present with sudden onset of vertigo, nausea, vomiting, tinnitus, and unilateral hearing loss, commonly from acute/chronic otitis media. 
Meningitis is a serious complication.

Acoustic Neuroma

Intracranial tumors developing from Schwann cells that myelinate the vestibular and/or cochlear nerve, usually from the vestibular portion. 
These tumors can grow significantly large and often take up much of the cerebellopontine angle.
Clinical features include unilateral hearing loss (most common), accompanied by tinnitus, facial nerve palsy, headache and/or balance difficulties, often only noticeable after a noticeable tumor growth.

Acoustic Neuroma (cont.)

The tumors rarely cause elevated intracranial pressure until quite large.
Diagnosis and treatment (microsurgery and radiation) usually yield good results in terms of patient survival.

Hematology 4 - Assorted Anemias and Disorders of Coagulation

This section focuses on different types of anemias, abnormal RBC production, and coagulation disorders. The outcomes include understanding etiology, pathophysiology, clinical presentation, laboratory assessment, and complications of diseases like megaloblastic anemias, and those from deficiency of copper or lead toxicity and vitamin B6. Moreover, this section will relate coagulation issues to Virchow's triad and investigate polycythemia vera, immune-related conditions and specific coagulation disorders.

Babesiosis

Parasitic infection caused by protozoa of the genus Babesia (microtus is most common in North America.)  
Primarily transmitted by tick bites (common in summer months).
Significant pathogen in small rodents and deer.
The disease is often characterized by anemia, with splenomegaly and possible splenic infarction in severe cases; General systemic symptoms of fatigue are also frequently present.

Babesiosis (cont.)

Risk factors include older age, absence or damage to the spleen.
Symptoms and signs include: gradual onset of fatigue, malaise, fever, chills, sweats; headache, myalgias, neck stiffness, nausea, vomiting.
Severe cases may also involve hemolitic anemia, and significant splenomegaly and/or infarction or acute respiratory distress, kidney injury (hemoglobinuria) and possibly heart problems.

Babesiosis (cont.)

Diagnosis involves microscopic examination of blood smear and PCR. 
Treatment combines macrolide antibiotics and antiparasitic agents. 
The infection frequently goes under-reported.

Coagulation Pathology - Hyper- and Hypo-coagulability

Hypercoagulability features include Virchow’s triad, which includes hypercoagulability, abnormalities of blood flow, and endothelial damage, and inherited coagulation cascade disorders or disorders of polycythemia vera. 
Hypo-coagulability can result from Von Willebrand disease, Acquired thrombocytopenias, or Disseminated intravascular coagulation.

Coagulation Pathology (cont.)

Virchow's triad of hypercoagulability, abnormal blood flow, and endothelial damage are significant in pathological coagulation.   
Abnormalities in blood flow, such as decreased shear stress in regions of turbulent or stagnant flow, can contribute to hypercoagulability.  
Excessive shear stress in the areas of narrowing or irregularly shaped blood vessels can stimulate platelets.

Coagulation Pathology (cont.)

Common inherited hypercoagulable conditions include Factor V Leiden (activated protein C resistance), Protein C or S deficiencies, Antithrombin deficiency. 
Acquired conditions increasing coagulation include estrogen-containing OCPs that increase production of Thrombin, factors II, VII, X, XII and fibrinogen.

Genetic pro-thrombotic states

Factor V Leiden (activated protein C resistance), a common autosomal dominant genetic condition, makes Factor V resistant to activated protein C, leading to higher risk of thrombosis.
This condition presents mildly in heterozygous individuals, but its severity increases to 60% in homozygotes (recurrent venous thrombosis) with greater risk of thrombosis.

Genetic pro-thrombotic states (cont.)

Prothrombin mutations (rare gene defect increase risk to 3x for VTE) and deficiencies in protein C, protein S, and antithrombin III contribute to a raised risk of thromboembolism in those that have the abnormalities.

Acquired Causes of Increased Clotting

Anti-phospholipid antibody syndrome (APS) is a hypercoagulable state with multiple antibodies to proteins C and S.  
This syndrome has a prevalence of 40-50/100,000, but can be related to pregnancy complications and venous or arterial thrombi, although a detailed discussion about its manifestation will occur in the future.

Deficient Clotting - Acquired Thrombocytopenias

Thrombocytopenia, characterized by deficient clotting, can be acquired from hypersplenism, destruction of platelets by autoantibodies, drug-induced effects (such as those from heparin), viral infections (e.g., HCV), or idiopathic thrombocytopenic purpura (ITP).
It can also result from excessive intravascular clotting (DIC), which can result from conditions like sepsis, hemolytic-uremic syndromes. or conditions as bone marrow infiltration/issues.

Immune thrombocytopenia (ITP)

Isolated thrombocytopenia arises when another condition is not present.  
Most common in children following viral illnesses or vaccinations; in adults often chronic, it doesn’t always resolve.
Bleeding, clinical purpura, often manifest as symptoms, but no coagulation factor issues are present.

ITP - Pathogenesis

Immune-mediated destruction of platelets, often after a viral infection or vaccination.
Cytotoxic T-cells may attack megakaryocytes and there might be inappropriate TPO levels for a deficiency in platelets, or over-activation of some T-cells.
HLA haplotypes seem to be associated but definite mechanistic links yet to solidify.

ITP - Clinical Features

Purpura (small bruises) and petechia, epistaxis, menorrhagia.  
Conditions that increase bleeding risks include using NSAIDs, antiplatelet drugs, GI bleeds, older age, and high blood pressure. 
Potentially severe risks including intracranial bleedings are possible in those with very low platelet counts (< 5000).

ITP

Mucocutaneous bleeding (purpura, epistaxis, gingival bleeding, menorrhagia,), worsening of GI bleeds, are common presentations in associated coagulation disorders.  
Glucocorticoids can aid in increasing platelet counts, and/or splenectomy to reduce platelet destruction is used in treatments. Some patients are given immunosuppressants.

Von Willebrand Disease (vWD)

vWD describes a common genetic disorder (autosomal dominant) of mild or variable severity (affecting 1% of the population in US adults), characterized by a deficiency of von Willebrand factor. 
Type 1 is a mild deficiency of vWF; Type 2 involves a malfunctioning vWF; Type 3 is a severe autosomal recessive deficiency.
vWF's crucial roles include stabilizing factor VIII, enabling platelet adhesion to subendothelial matrix (via GPIb/IX, GPIIb/IIIa), and acute release in response to vascular damage.

Von Willebrand Disease (cont.)

Common signs and symptoms of vWD include defects in platelet function, despite a normal platelet count.
Mucosal bleeding, easy bruising, epistaxis, hematuria, menorrhagia, and prolonged bleeding from wounds—although hemarthroses are uncommon in vWD.  
Vasopressin (ADH) is a treatment option, as it's involved in the release of vWF from endothelial cells to augment the levels.

Disseminated Intravascular Coagulation (DIC)

Severe, life-threatening coagulation disorder characterized by widespread activation of the coagulation system leads to microthrombi throughout the blood vessels, consuming clotting factors, and potentially leading to hemorrhage.   
Underlying conditions (like sepsis, trauma, or malignancy) trigger DIC, often leading to severe complications such as organ damage and bleeding.

Disseminated Intravascular Coagulation (cont.)

Pathophysiological triggers in DIC include tissue factor or thromboplastic substances entering the circulation, activation/damage of endothelial cells, or release from tissue damage and/or from acute promyelocytic leukemia cells, to organ-specific tissue damage.
DIC is characterized by low platelet counts and low levels of clotting factors, and is frequently associated with increased fibrin degradation products.  
Severe forms usually result from underlying conditions such as infection, trauma, or cancer.   Signs/symptoms may include acute or chronic states of otalgia, fever, and severe vascular changes to organs or tissue.

Excessive RBC Production, Anemias, and Associated Conditions

Excessive RBC production include diseases like polycythemia vera,
Anemias encompass various types, including megaloblastic anemias arising from insufficient DNA synthesis (often due to B12 or folate deficiency), autoimmune hemolytic anemia (AIHA) with differing mechanisms with antibody attacks on RBCs, and various other rarer causes like copper deficiency, lead toxicity, and vitamin B6 deficiency.

Polycythemia Vera

Polycythemia vera (PV) is a myeloproliferative disorder, a type of cancer affecting hematopoietic cells. 
A clonal stem cell disorder, PV involves the excessive production of red blood cells, white blood cells, and platelets.  
PV is characterized by a chronic increase in blood volume, often occurring in individuals over 50, as well as presence of symptoms, such as headaches, vertigo and visual problems due to high Hb and hematocrit values.

Polycythemia Vera (cont.)

Clinical features of PV are often asymptomatic, but can be characterized by high Hb or hematocrit, leading to neurologic symptoms like headache, vertigo, and visual changes.
Cardiovascular events are common, including possible issues in cerebral, cardiac, and mesenteric vessels; and in venous vessels like the hepatic vein, and/or thrombosis in the deep veins (DVT) or pulmonary embolus (PE).