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Healing of damaged tissues, healing disorders

185.174.171.80 — Thu, 07 May 2026 19:15:14 GMT

Created page with "Healing is the body’s biological response to tissue injury aimed at restoring structural integrity and function. It involves highly coordinated cellular, vascular, biochemical, and extracellular matrix processes. The goals of healing are: * Prevention of blood loss * Elimination of microorganisms * Removal of necrotic tissue * Restoration of tissue continuity * Recovery of function Healing depends on: * Type and extent of injury * Blood supply * Presence of infecti..."

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Healing is the body’s biological response to tissue injury aimed at restoring structural integrity and function. It involves highly coordinated cellular, vascular, biochemical, and extracellular matrix processes.

The goals of healing are:

* Prevention of blood loss
* Elimination of microorganisms
* Removal of necrotic tissue
* Restoration of tissue continuity
* Recovery of function

Healing depends on:

* Type and extent of injury
* Blood supply
* Presence of infection
* Nutritional status
* Age and systemic health

= Types of Cells Involved in Healing =
{| class="wikitable"
!Cell Type
!Characteristics
!Examples
|-
|Labile cells
|Continuously dividing
|Skin epithelium, bone marrow
|-
|Stable cells
|Quiescent but capable of division
|Hepatocytes, fibroblasts
|-
|Permanent cells
|Minimal or no proliferative capacity
|Neurons, cardiac muscle cells
|}

= Regeneration and Repair =

== Regeneration ==
Regeneration is replacement of damaged tissue by the same type of functional cells.

=== Features ===

* Complete restoration of structure and function
* Requires viable stem cells
* Extracellular matrix scaffold remains intact

=== Examples ===

* Liver regeneration
* Regeneration of skin epithelium
* Hematopoietic tissue renewal

== Repair ==
Repair is replacement of injured tissue by connective tissue and scar formation.

=== Features ===

* Occurs when injury is severe
* Functional tissue replaced by fibrosis
* May result in permanent loss of function

=== Examples ===

* Myocardial infarction healing
* Deep skin wounds

= Phases of Healing =
Healing occurs in overlapping phases.

= 1. Hemostasis Phase =
Occurs immediately after injury.

=== Events ===

* Vasoconstriction
* Platelet aggregation
* Activation of coagulation cascade
* Fibrin clot formation

=== Functions ===

* Prevent blood loss
* Provide scaffold for inflammatory cells
* Release growth factors

=== Important Mediators ===

* Platelet-derived growth factor (PDGF)
* Transforming growth factor-beta (TGF-β)

= 2. Inflammatory Phase =
Usually lasts for 1–3 days.

=== Cellular Components ===

==== Neutrophils ====

* First inflammatory cells to arrive
* Remove bacteria and debris through phagocytosis

==== Macrophages ====

* Replace neutrophils after 24–48 hours
* Most important cells in healing

=== Functions of Macrophages ===

* Phagocytosis
* Cytokine secretion
* Growth factor release
* Stimulation of angiogenesis and fibrosis

=== Major Cytokines ===

* IL-1
* TNF-α
* TGF-β
* VEGF

= 3. Proliferative Phase =
Occurs from day 3 onward.

Main processes include:

* Granulation tissue formation
* Angiogenesis
* Fibroblast proliferation
* Collagen synthesis
* Re-epithelialization

== Granulation Tissue ==
Granulation tissue consists of:

* Newly formed capillaries
* Fibroblasts
* Loose extracellular matrix
* Inflammatory cells

=== Appearance ===

* Soft
* Pink
* Granular

== Angiogenesis ==
Formation of new blood vessels from preexisting vessels.

=== Steps ===

# Vasodilation
# Migration of endothelial cells
# Endothelial proliferation
# Capillary tube formation
# Vessel maturation

=== Important Growth Factors ===

* VEGF
* Fibroblast growth factor (FGF)

== Fibroblast Proliferation ==
Fibroblasts synthesize extracellular matrix proteins.

=== Components Produced ===

* Collagen
* Elastin
* Proteoglycans
* Fibronectin

Initially:

* Type III collagen predominates

Later:

* Replaced by stronger Type I collagen

== Re-epithelialization ==
Migration and proliferation of epithelial cells over the wound surface restore surface continuity.

= 4. Remodeling Phase =
Begins around the third week and may continue for months.

=== Features ===

* Collagen remodeling
* Increased tensile strength
* Decreased vascularity
* Scar maturation

=== Important Enzymes ===

* Matrix metalloproteinases (MMPs)

=== Tensile Strength ===
Healed tissue reaches approximately 70–80% of original strength.

= Healing by Primary and Secondary Intention =

== Healing by Primary Intention ==
Occurs in clean wounds with closely approximated edges.

=== Features ===

* Minimal tissue loss
* Minimal granulation tissue
* Rapid epithelial regeneration
* Small scar formation

=== Example ===

* Surgical incision closed with sutures

== Healing by Secondary Intention ==
Occurs in large wounds with extensive tissue loss.

=== Features ===

* More inflammation
* Large amount of granulation tissue
* Wound contraction
* Larger scar

=== Role of Myofibroblasts ===
Myofibroblasts mediate wound contraction.

= Healing of Specific Tissues =

= Skin Wound Healing =

== Partial-Thickness Wounds ==

* Heal mainly by regeneration

== Full-Thickness Wounds ==

* Heal by granulation tissue formation and scarring

= Bone Healing =

=== Stages ===

# Hematoma formation
# Soft callus formation
# Hard callus formation
# Bone remodeling

=== Cells Involved ===

* Osteoblasts
* Osteoclasts
* Chondroblasts

= Fracture Healing =

== Primary Bone Healing ==

* Direct bone remodeling
* Requires rigid fixation

== Secondary Bone Healing ==

* Most common type
* Involves callus formation

= Liver Regeneration =
The liver possesses remarkable regenerative ability.

=== Mechanism ===
Compensatory hyperplasia of surviving hepatocytes.

=== Major Stimulators ===

* Hepatocyte growth factor (HGF)
* IL-6
* TNF-α

= Factors Affecting Wound Healing =

= Local Factors =
{| class="wikitable"
!Factor
!Effect
|-
|Infection
|Delays healing
|-
|Poor blood supply
|Causes hypoxia
|-
|Foreign bodies
|Maintain inflammation
|-
|Mechanical stress
|Causes wound disruption
|-
|Edema
|Impairs oxygen diffusion
|}

= Systemic Factors =
{| class="wikitable"
!Factor
!Effect
|-
|Malnutrition
|Reduced collagen synthesis
|-
|Vitamin C deficiency
|Defective collagen formation
|-
|Diabetes mellitus
|Poor angiogenesis and infection
|-
|Glucocorticoids
|Suppress inflammation
|-
|Smoking
|Causes vasoconstriction
|-
|Advanced age
|Slows repair
|}

= Extracellular Matrix in Healing =
The extracellular matrix provides:

* Structural support
* Cell adhesion
* Reservoir for growth factors
* Regulation of cell behavior

=== Components ===

* Collagen
* Laminin
* Fibronectin
* Proteoglycans

= Important Growth Factors =
{| class="wikitable"
!Growth Factor
!Main Function
|-
|PDGF
|Fibroblast migration
|-
|VEGF
|Angiogenesis
|-
|FGF
|Fibroblast proliferation
|-
|TGF-β
|Fibrosis and collagen synthesis
|-
|EGF
|Epithelial regeneration
|}

= Healing Disorders =
Abnormal healing may result from inadequate repair or excessive tissue response.

= Wound Dehiscence =

== Definition ==
Partial or complete reopening of a wound.

== Causes ==

* Infection
* Poor suturing
* Increased mechanical stress
* Malnutrition

= Ulcer Formation =

== Definition ==
Loss of epithelial surface due to necrosis and inflammation.

== Common Causes ==

* Venous insufficiency
* Diabetes mellitus
* Arterial disease
* Pressure injury

= Hypertrophic Scar =

=== Features ===

* Excess collagen deposition
* Raised scar
* Remains within wound boundaries

=== Pathogenesis ===
Excessive fibroblast activity.

= Keloid =

=== Features ===

* Excessive scar tissue extending beyond wound margins
* High recurrence rate after removal

=== Pathogenesis ===

* Increased collagen synthesis
* Increased TGF-β activity

=== Common Sites ===

* Earlobes
* Sternum
* Shoulders

= Excessive Granulation Tissue (Proud Flesh) =

=== Features ===

* Granulation tissue protrudes above skin level
* Prevents epithelial regeneration

=== Treatment ===

* Surgical removal
* Cauterization

= Contractures =

== Definition ==
Excessive wound contraction causing deformity.

== Common After ==

* Severe burns

== Consequences ==

* Joint deformity
* Restricted movement

= Fibrosis =

== Definition ==
Excessive deposition of collagen in tissues.

== Causes ==

* Chronic inflammation
* Persistent tissue injury

== Examples ==

* Pulmonary fibrosis
* Liver cirrhosis

= Chronic Wounds =

== Definition ==
Wounds that fail to heal in the expected period.

== Characteristics ==

* Persistent inflammation
* Impaired angiogenesis
* Biofilm formation
* Cellular senescence

== Examples ==

* Diabetic foot ulcers
* Pressure ulcers
* Venous ulcers

= Impaired Healing in Diabetes Mellitus =

== Mechanisms ==

* Microvascular disease
* Neuropathy
* Reduced leukocyte function
* Chronic inflammation
* Impaired angiogenesis

== Consequences ==

* Delayed healing
* Increased infection risk
* Chronic ulcer formation

= Molecular Basis of Fibrosis =
Persistent injury causes:

# Chronic macrophage activation
# Release of TGF-β
# Fibroblast proliferation
# Excess extracellular matrix deposition

=== Major Fibrogenic Cytokine ===
TGF-β

= Clinical Correlation =

= Pressure Ulcers =
Caused by prolonged ischemia over bony prominences.

=== Risk Factors ===

* Immobility
* Malnutrition
* Neurological disease

= Diabetic Foot Ulcers =
Result from:

* Peripheral neuropathy
* Ischemia
* Infection

= Burn Healing =

== Partial-Thickness Burns ==
May heal by regeneration.

== Full-Thickness Burns<ref>Robbins and Cotran Pathologic Basis of Disease Kumar V, Abbas AK, Aster JC. ''Robbins and Cotran Pathologic Basis of Disease''. 10th ed. Elsevier; 2021.

Robbins Basic Pathology Kumar V, Abbas AK, Aster JC. ''Robbins Basic Pathology''. 11th ed. Elsevier; 2023.

Guyton and Hall Textbook of Medical Physiology Hall JE. ''Guyton and Hall Textbook of Medical Physiology''. 14th ed. Elsevier; 2021.</ref> ==
Heal with fibrosis and may require grafting.

Hepatitis, toxic and metabolic liver damage, liver steatosis, steatohepatitis

Simon Katzemich — Thu, 07 May 2026 08:24:41 GMT

← Older revision		Revision as of 10:24, 7 May 2026
Line 147:		Line 147:

	* '''Medical History & Physical Exam:''' Checking for an enlarged liver or signs of jaundice.		* '''Medical History & Physical Exam:''' Checking for an enlarged liver or signs of jaundice.
	* '''Imaging:''' Ultrasound, CT scans, or MRIs. A specialized test called ~~'''FibroScan®'''~~ can quantify the amount of fat and scar tissue.		* '''Imaging:''' Ultrasound, CT scans, or MRIs. A specialized test called FibroScan can quantify the amount of fat and scar tissue.
	* '''Liver Biopsy:''' A tissue sample is the gold standard, particularly to distinguish between MASLD and MASH.		* '''Liver Biopsy:''' A tissue sample is the gold standard, particularly to distinguish between MASLD and MASH.

Ovulation and Menstrual Disorders

86.49.240.144 — Wed, 06 May 2026 20:40:56 GMT

@@ Line 1: / Line 1: @@
 == Overview ==
-The '''menstrual cycle''' is a complex, hormone-regulated physiological process that prepares the female body for potential pregnancy. It involves coordinated interactions between the '''hypothalamus, pituitary gland, and ovaries''', resulting in the maturation and release of an oocyte and cyclical changes in the endometrium.
+The '''[[menstrual cycle]]''' is a complex, hormone-regulated physiological process that prepares the female body for potential [[pregnancy]]. It involves coordinated interactions between the '''[[hypothalamus]], [[pituitary gland]], and [[ovaries]]''', resulting in the maturation and release of an oocyte and cyclical changes in the endometrium.
 A typical cycle lasts about '''28 days''' (range: 24–38 days) and consists of two interrelated components:
-* '''Ovarian cycle'''
+* '''[[Ovarian cycle]]'''
 ** '''Follicular phase''': maturation of ovarian follicles
 ** '''Ovulation''': release of the oocyte (triggered by a surge in luteinizing hormone)
@@ Line 23: / Line 23: @@
 * pituitary gland
 * ovaries
-* endometrium
+* [[endometrium]]
 Disruption at any level of this axis may produce abnormal ovulation or menstrual irregularity.
@@ Line 74: / Line 74: @@
 * irregular periods
-* hyperandrogenism
+* [[hyperandrogenism]]
 * infertility
-* acne and hirsutism
+* acne and [[hirsutism]]
-* polycystic ovaries
+* [[polycystic ovaries]]
 <u>'''Long-term associations:'''</u>
@@ Line 84: / Line 84: @@
 * metabolic syndrome
 * cardiovascular risk
-* endometrial hyperplasia
+* [[endometrial hyperplasia]]
 Persistent irregular cycles may also correlate with cardiometabolic disease.
@@ Line 140: / Line 140: @@
 associated with:
-* '''Endometriosis'''
+* '''[[Endometriosis]]'''
 * fibroids
 * adenomyosis
@@ Line 163: / Line 163: @@
 ** Classified as a depressive disorder
-== Anovulatory cycles ==
+== Anovulatory Cycles ==
 === '''Definition''' ===
@@ Line 179: / Line 179: @@
 * Heavy or prolonged bleeding
 * Common in early years after menarche

Ovulation and Menstrual Disorders

86.49.240.144 — Wed, 06 May 2026 19:31:35 GMT

Created page with "== Overview == The '''menstrual cycle''' is a complex, hormone-regulated physiological process that prepares the female body for potential pregnancy. It involves coordinated interactions between the '''hypothalamus, pituitary gland, and ovaries''', resulting in the maturation and release of an oocyte and cyclical changes in the endometrium. A typical cycle lasts about '''28 days''' (range: 24–38 days) and consists of two interrelated components: * '''Ovarian cycle'''..."

New page

== Overview ==
The '''menstrual cycle''' is a complex, hormone-regulated physiological process that prepares the female body for potential pregnancy. It involves coordinated interactions between the '''hypothalamus, pituitary gland, and ovaries''', resulting in the maturation and release of an oocyte and cyclical changes in the endometrium.

A typical cycle lasts about '''28 days''' (range: 24–38 days) and consists of two interrelated components:

* '''Ovarian cycle'''
** '''Follicular phase''': maturation of ovarian follicles
** '''Ovulation''': release of the oocyte (triggered by a surge in luteinizing hormone)
** '''Luteal phase''': formation and regression of the corpus luteum
* '''Uterine cycle'''
** '''Menstrual phase''': shedding of the endometrium
** '''Proliferative phase''': endometrial regeneration
** '''Secretory phase''': preparation for implantation

Ovulation typically occurs around day 14 and is essential for fertility.

== Introduction ==
'''Ovulatory and menstrual disorders''' are common gynecologic conditions involving disruption of the normal menstrual cycle, ovulation, or uterine bleeding patterns. These disorders affect reproductive health, fertility, metabolic function, bone health, and cardiovascular risk.

The menstrual cycle is regulated through coordinated interaction between:

* hypothalamus
* pituitary gland
* ovaries
* endometrium

Disruption at any level of this axis may produce abnormal ovulation or menstrual irregularity.

== Ovulatory Disorders ==

=== '''Definition''' ===
efers to abnormal, infrequent, or absent ovulation. These conditions are among the most common causes of female infertility.

=== '''Types of Ovulatory disorders''' ===

==== '''Anovulation -''' complete absence of ovulation ====
Manifestations:

* irregular menstruation
* amenorrhea
* infertility
* abnormal uterine bleeding

==== '''Oligoovulation -''' infrequent or irregular ovulation ====
Often associated with:

* long menstrual cycles (>35 days)
* unpredictable bleeding

=== '''Classification Systems''' ===
{| class="wikitable"
!'''Category'''
!'''Site of dysfunction'''
|-
|'''Hypothalamic'''
|'''GnRH dysfunction'''
|-
|'''Pituitary'''
|'''Pituitary hormone disorders'''
|-
|'''Ovarian'''
|'''Primary ovarian dysfunction'''
|-
|'''PCOS'''
|'''Polycystic ovary syndrome'''
|}

=== '''Major Causes of Ovulatory Disorders''' ===

==== Polycystic Ovary Syndrome (PCOS) ====
The leading cause of chronic anovulation.

'''Features:'''

* irregular periods
* hyperandrogenism
* infertility
* acne and hirsutism
* polycystic ovaries

'''Long-term associations:'''

* insulin resistance
* metabolic syndrome
* cardiovascular risk
* endometrial hyperplasia

Persistent irregular cycles may also correlate with cardiometabolic disease.

==== Hypothalamic Amenorrhea ====
'''Causes:'''

* psychological stress
* excessive exercise
* eating disorders
* low body weight

'''Mechanism:'''

* reduced GnRH secretion
* decreased LH/FSH production
* suppression of ovulation

==== '''Hyperprolactinemia''' ====
Elevated prolactin inhibits GnRH secretion and impairs ovulation.

'''Causes:'''

* pituitary adenoma
* medications
* hypothyroidism

==== '''Premature Ovarian Insufficiency''' ====
Defined as ovarian dysfunction before age 40.

'''Manifestations:'''

* amenorrhea
* infertility
* hypoestrogenism

== Menstrual Disorders ==

=== '''Definition''' ===
Menstrual disorders are abnormalities in '''frequency, regularity, duration, or volume of menstrual bleeding'''.

==== Amenorrhea ====

* '''Primary amenorrhea''': absence of menarche

* '''Secondary amenorrhea''': cessation of established menstruation

==== Dysmenorrhea ====

===== Primary dysmenorrhea =====

* prostaglandin-mediated uterine contractions

===== Secondary dysmenorrhea =====
associated with:

* '''Endometriosis'''
* fibroids
* adenomyosis
* Painful menstruation
* Typically occurs during the menstrual phase

==== Abnormal Uterine Bleeding ====

* Includes:
** '''Heavy menstrual bleeding'''
** '''Irregular or frequent bleeding'''

* Often associated with '''anovulatory cycles'''

==== Premenstrual disorder ====
Occur during the luteal phase and resolve with menstruation.

* '''Premenstrual syndrome (PMS)'''
** Mild to moderate physical and emotional symptoms
* '''Premenstrual dysphoric disorder (PMDD)'''
** Severe form with significant impact on daily functioning
** Classified as a depressive disorder

== Anovulatory cycles ==

=== '''Definition''' ===
Anovulatory cycles are a key link between ovulatory and menstrual disorders.

=== '''Mechanism''' ===

* Immature or disrupted HPO axis → irregular gonadotropin release
* No ovulation → no progesterone
* Endometrium continues to proliferate under estrogen

=== '''Clinical Impact''' ===

* Irregular menstruation
* Heavy or prolonged bleeding
* Common in early years after menarche

Constipation, Diverticulosis, Megacolon

86.49.240.144 — Wed, 06 May 2026 19:02:40 GMT

← Older revision		Revision as of 21:02, 6 May 2026
Line 46:		Line 46:
	\|-		\|-
	\|		\|
	* Normal-transit constipation
	* Slow-transit constipation

	* ~~Defecatory~~ disorders		* Infrequent bowel movements
	~~\|Common causes:~~		* '''Hard stools'''
			* '''Straining during defecation'''
			* Sensation of '''incomplete evacuation'''
			* Difficulty passing stool (even when soft, in defecatory disorders)
			* '''Abdominal bloating'''
			* Mild abdominal discomfort or cramping

	* ~~Low fiber intake~~		* Reduced urge to defecate (especially in slow-transit type)
	* ~~[[Dehydration]]~~		\|
	* ~~Sedentary lifestyle~~		* Similar core symptoms (infrequent, hard stools, straining)
	* ~~Medications~~:		* '''Change in bowel habits''' (often new or worsening)
	** ~~opioids~~		* Symptoms related to the '''underlying cause''', which may include:
	** anticholinergics		** Abdominal pain (e.g., obstruction)
	** ~~iron supplements~~		** Nausea or bloating
	* Systemic diseases:
	** [[hypothyroidism]]		* May be associated with '''systemic or additional symptoms''' depending on the condition (e.g., neurological or metabolic features)
	** [[Diabetes mellitus\|diabetes]]
	** neurologic disorders
	\|}		\|}

Constipation, Diverticulosis, Megacolon

Vadim — Tue, 05 May 2026 17:56:03 GMT

Show changes

File:Diverticulum.png

Vadim — Tue, 05 May 2026 17:34:27 GMT

Vadim uploaded File:Diverticulum.png

New page

diverticulum

Constipation, Diverticulosis, Megacolon

88.101.32.31 — Tue, 05 May 2026 17:28:42 GMT

Created page with "== General information == '''Constipation, diverticulosis, and megacolon''' are conditions affecting the large intestine that vary in severity, underlying mechanisms, and clinical significance. Constipation is a common functional gastrointestinal disorder characterized by infrequent or difficult bowel movements and may arise from disturbances in colonic motility or defecation. Diverticulosis refers to the presence of multiple diverticula-outpouchings of the colonic wall-..."

New page

== General information ==
'''Constipation, diverticulosis, and megacolon''' are conditions affecting the large intestine that vary in severity, underlying mechanisms, and clinical significance. Constipation is a common functional gastrointestinal disorder characterized by infrequent or difficult bowel movements and may arise from disturbances in colonic motility or defecation. Diverticulosis refers to the presence of multiple diverticula-outpouchings of the colonic wall-most commonly associated with increased intraluminal pressure and structural weakness of the bowel.

Megacolon, in contrast, represents a pathological dilation of the colon without mechanical obstruction and may occur in acute, chronic, or toxic forms. While constipation and diverticulosis are often chronic and frequently asymptomatic or mild, megacolon can present as a severe and potentially life-threatening condition, particularly in its toxic variant.

Together, these disorders illustrate the spectrum of colonic dysfunction, encompassing abnormalities in motility, structure, and systemic involvement.

== Constipation ==

=== '''Definition''' ===
Constipation is a common gastrointestinal condition characterized by:

* Fewer than '''3 bowel movements per week''' (not required for diagnosis)
* '''Hard stools'''
* '''Straining'''
* '''Sensation of incomplete evacuation'''
* Possible need for manual assistance (e.g., self-digitation)

=== '''Classification''' ===
{| class="wikitable"
!Primary (functional) constipation
!Secondary constipation
|-
|
* Normal transit constipation (most common)
* '''Slow-transit constipation''' (delayed colonic movement due to neuromuscular dysfunction)

* Defecatory disorders (e.g., pelvic dyssynergia)
|
* Medications
* Metabolic or neurological disorders
* Mechanical obstruction
|}

=== '''Pathophysiology''' ===

* Neuromuscular dysfunction of the colon
* Loss of '''interstitial cells of Cajal'''

* Impaired peristalsis due to disrupted neural control

=== '''Clinical features''' ===
{| class="wikitable"
!Primary (functional) constipation
!Secondary constipation
|-
|
* Normal-transit constipation
* Slow-transit constipation

* Defecatory disorders
|Common causes:

* Low fiber intake
* Dehydration
* Sedentary lifestyle
* Medications:
** opioids
** anticholinergics
** iron supplements
* Systemic diseases:
** hypothyroidism
** diabetes
** neurologic disorders
|}

=== '''Treatment''' ===
'''Initial (nonpharmacologic)'''

* Increased '''fiber and fluid intake'''
* Behavioral modifications (avoid stool withholding)

'''Pharmacologic'''

* Bulk-forming laxatives
* Osmotic laxatives
* Stimulant laxatives or secretagogues (if needed)

'''Further evaluation'''

* Indicated if refractory symptoms or red flags (e.g., malignancy suspicion)

== Diverticulosis ==

=== '''Definition''' ===
Diverticulosis refers to the presence of '''diverticula''' (outpouchings of the colonic wall), typically without inflammation.

=== '''Clinical presentation''' ===

* Often '''asymptomatic'''

* May be associated with nonspecific gastrointestinal symptoms:
** mild abdominal discomfort
** bloating
** altered bowel habits (constipation or diarrhea)

=== '''Formation of Diverticula''' ===
Diverticula are '''mucosal and submucosal herniations''' through weak points in the colonic muscular wall

Most commonly occur in the '''sigmoid colon''' due to:

* higher intraluminal pressure
* smaller diameter

Key mechanism:

Increased colonic pressure → focal wall weakness → outpouching

=== '''Epidemiology''' ===
Prevalence increases with age:

* <40 years: uncommon
* 60 years: very common

=== '''Treatment''' ===
'''Asymptomatic diverticulosis'''

* No treatment reverses diverticula formation
* Focus on '''preventing progression'''

'''Symptomatic uncomplicated disease'''

* Evidence for therapies (e.g., antibiotics, probiotics) is unclear
* Symptoms may overlap with irritable bowel syndrome

'''Complicated disease'''

* Includes diverticulitis and requires separate management

==== '''Diverticulitis''' ====
is the inflammation or infection of colonic diverticula, most commonly occurring as a complication of diverticulosis. It typically presents with '''left lower quadrant abdominal pain''', '''fever''', and changes in bowel habits such as constipation or diarrhea, reflecting involvement of the sigmoid colon. The condition can range from mild, localized inflammation (uncomplicated diverticulitis) to more severe forms associated with complications such as abscess formation or perforation. Diagnosis is usually confirmed with '''CT imaging''', and management depends on severity, with conservative treatment for mild cases and more aggressive interventions, including antibiotics or surgery, for complicated disease.

== Megacolon ==

=== '''Definition''' ===
Megacolon is '''abnormal dilation of the colon''' without a mechanical obstruction. Core mechanisms include:

* Failure of colonic smooth muscle contraction
* Dysfunction of the '''enteric nervous system'''
* Severe inflammation (in acute cases)

Result:

* Progressive accumulation of gas and feces
* Marked dilation (often >6 cm in transverse colon)

=== '''Types''' ===

# '''Acute megacolon (Ogilvie syndrome)'''
# '''Chronic megacolon'''
# '''Toxic megacolon''' (life-threatening)

==== '''Acute Megacolon (Ogilvie Syndrome)''' ====

===== '''Etiology''' =====

* Occurs in '''severely ill or postoperative patients'''

* Associated factors:
** Electrolyte imbalances
** Medications (e.g., opioids, anticholinergics)
** Trauma or surgery

===== '''Pathophysiology''' =====
Autonomic imbalance → impaired motility → accumulation of gas and feces → colonic dilation

===== '''Clinical features''' =====

* Abdominal distention (gradual)
* Abdominal pain
* Constipation or diarrhea

* Reduced bowel sounds

===== '''Diagnosis''' =====

* '''Abdominal X-ray''': colonic dilation with preserved haustra

* '''CT scan''': excludes obstruction and detects complications

===== '''Treatment''' =====
'''Conservative'''

* Bowel rest (NPO)
* IV fluids
* Decompression (NG tube, rectal tube)
* Treat underlying cause

'''Pharmacologic'''

* '''Neostigmine'''

'''Procedural/Surgical'''

* Colonoscopic decompression
* Surgery if complications or treatment failure

==== '''Chronic megacolon''' ====
Persistent colonic dilation due to:

* '''Neuropathic disorders''' (e.g., Hirschsprung disease)
* '''Myopathic disorders'''

===== '''Symptoms''' =====

* Chronic constipation

* Abdominal distention

==== '''Toxic megacolon''' ====

===== '''Definition''' =====
A '''life-threatening''' complication with:

* Colonic dilation
* '''Systemic toxicity'''

===== '''Causes''' =====

* Infectious colitis (e.g., ''C. difficile'')

* Inflammatory bowel disease

===== '''Clinical features''' =====

* Fever, tachycardia, hypotension
* Abdominal pain

* Bloody diarrhea

===== '''Treatment''' =====
'''Emergency treatment'''

* Bowel rest
* IV antibiotics (if infectious)
* IV steroids (if inflammatory)

'''Surgery'''

* Indicated if no improvement within 24–72 hours
* Typically '''subtotal colectomy'''

Tubulointerstitial nephritis New

Karineliav — Mon, 04 May 2026 20:14:21 GMT

← Older revision		Revision as of 22:14, 4 May 2026
Line 1:		Line 1:
			[[File:Chronic Nephritis .jpg\|thumb]]
	Tubulointerstitial nephritis (TIN) is a heterogeneous group of [[kidney]] diseases characterized by inflammation and injury of the [[renal tubules]] and interstitium, with relative sparing of the glomeruli.		Tubulointerstitial nephritis (TIN) is a heterogeneous group of [[kidney]] diseases characterized by inflammation and injury of the [[renal tubules]] and interstitium, with relative sparing of the glomeruli.

File:Chronic Nephritis .jpg

Karineliav — Mon, 04 May 2026 20:14:02 GMT

Karineliav uploaded File:Chronic Nephritis .jpg

New page

Chronic Nephritis

Tubulointerstitial nephritis New

86.49.241.148 — Mon, 04 May 2026 20:09:34 GMT

Classification of TIN

Show changes

Tubulointerstitial nephritis New

86.49.241.148 — Mon, 04 May 2026 19:45:27 GMT

Created page with "Tubulointerstitial nephritis (TIN) is a heterogeneous group of kidney diseases characterized by inflammation and injury of the renal tubules and interstitium, with relative sparing of the glomeruli. It represents an important cause of acute kidney injury (AKI) and may progress to chronic kidney disease (CKD) if untreated. == Classification of TIN == ==== '''According to duration''' ==== * Acute tubulointerstitial nephritis (ATIN) ** Sudden onset ** Often revers..."

New page

Tubulointerstitial nephritis (TIN) is a heterogeneous group of kidney diseases characterized by inflammation and injury of the renal tubules and interstitium, with relative sparing of the glomeruli.

It represents an important cause of acute kidney injury (AKI) and may progress to chronic kidney disease (CKD) if untreated.

== Classification of TIN ==

==== '''According to duration''' ====

* Acute tubulointerstitial nephritis (ATIN)
** Sudden onset
** Often reversible
* Chronic tubulointerstitial nephritis (CTIN)
** Gradual progression
** Leads to fibrosis and irreversible damage

==== '''According to etiology''' ====

* Drug-induced (most common)
* Infectious
* Autoimmune/systemic
* Metabolic/toxic
* Idiopathic

{| style="width: 80%; background-color: transparent;text-align: left; margin-bottom: 10px; border: 1px solid #7AC5CD; "
| class="portaltitle" style="background-color: #7AC5CD; text-align: center; font-weight: bold;" |
* Drug-induced (most common)
* Infectious
* Autoimmune/systemic
* Metabolic/toxic
* Idiopathic
|-
|
{| class="sb_portal sbaleno" style="width: 100%; vertical-align: top; background-color: transparent;"
| style="width: 50%;vertical-align: top;" |<div style="background-color: #7AC5CD; text-align: center; font-weight: bold;">Acute tubulointerstitial nephritis</div>
*acute bacterial TIN,
*acute hypersensitivity TIN (drug, especially ATB, NSAID),
*parainfectious TIN,
*idiopathic TIN.
| style="width: 50%;vertical-align: top;" |<div style="background-color: #7AC5CD; text-align: center; font-weight: bold;">Chronic tubulointerstitial nephritis</div>
*chronic bacterial TIN,
*analgesic nephropathy,
*reflux nephropathy,
*drug nephropathy,
*Li and heavy metal poisoning,
*post-radiation nephropathy,
*nephropathy in systemic diseases (only glomerulonephritis may not occur in SLE or RA),
*nephropathy in malignant diseases,
*metabolic nephropathy,
*endemic Balkan nephropathy.
|}
|}

== Characteristics of TIN ==

* Proteinuria (usually mild to moderate, tubular type)
* Non-glomerular hematuria
* Leukocyturia (especially in infectious or inflammatory forms)
* Dysuria (mainly in infectious etiologies)

Tubular dysfunction may also lead to:

* impaired urine concentrating ability
* electrolyte disturbances (e.g., acidosis, potassium imbalance)

== Acute TIN ==
Acute forms are characterized by rapid onset of renal dysfunction associated with inflammatory infiltration of the interstitium.
includes:

* Acute bacterial TIN
* Acute hypersensitivity (drug-induced) TIN
* Parainfectious TIN
* Idiopathic forms

=== '''Acute bacterial TIN''' ===
Most commonly arises from ascending urinary tract infection.
Predisposing factors:

* Congenital anomalies (e.g., duplex kidney, vesicoureteral reflux)
* Urinary obstruction (lithiasis, strictures, prostatic enlargement)

==== Clinical presentation ====

* Fever and systemic inflammatory signs
* Flank or lumbar pain
* Dysuria and urinary frequency
* Possible oliguria

==== Examination ====
Physical findings:

* shortness of breath, sweating, febrile illness, often accompanied by chills
* active occupation of the relief position
* positive tapottement

Urinalysis:

* leukocyturia (constant)
* bacteriuria should also always be present. If the detection of bacteria fails, the possibility of TB infection must be considered
* non-glomerular erythrocyturia
* proteinuria usually <2 g/day

Laboratory tests:

* leukocytosis
* elevated inflammatory markers

Microbiology:

* urine culture mandatory (commonly E. coli, Klebsiella)

Imaging:

* ultrasound may show inflammatory changes

Renal biopsy is generally not required in typical cases.

==== Therapy ====

* Empirical antibiotics → adjusted according to culture
* Common regimens include cephalosporins, aminoglycosides, fluoroquinolones
* Treatment duration: usually ≥2 weeks

=== '''Acute hypersensitivity TIN''' ===
This form is typically drug-induced (e.g., antibiotics, NSAIDs).

==== Pathogenesis ====
Immune-mediated reaction with interstitial infiltration by lymphocytes and eosinophils.

==== Clinical features ====

* Fever
* Skin rash
* Arthralgia
* Renal dysfunction

Latency of 1–6 weeks after drug exposure is typical.

==== Examination ====
Urine findings

* non-glomerular hematuria
* eosinophiluria
* variable proteinuria

Blood tests

* eosinophilia (suggestive but not universal)

Biopsy

* interstitial inflammation ± granulomas

==== Therapy ====

* Immediate withdrawal of the causative drug
* Corticosteroids if renal function does not improve

== Chronic TIN ==
Chronic forms are characterized by progressive interstitial fibrosis and tubular atrophy, leading to irreversible renal damage. Main types:

* Chronic bacterial TIN
* Reflux nephropathy
* Analgesic nephropathy
* Toxic/metabolic nephropathies

=== '''Chronic bacterial TIN''' ===
Usually develops after recurrent acute infections.

==== Clinical features ====

* often asymptomatic between episodes
* gradual decline in renal function

==== Findings ====

* persistent leukocyturia
* bacteriuria
* mild proteinuria

==== Therapy ====

* treatment of acute exacerbations
* long-term prevention in recurrent cases

=== '''Reflux nephropathy''' ===
Associated with vesicoureteral reflux (VUR) leading to repeated renal injury.

==== Pathogenesis ====
Retrograde urine flow → recurrent infections → scarring.

==== Clinical features ====

* recurrent UTIs (especially in childhood)
* enuresis in children
* later: hypertension, renal insufficiency

==== Diagnosis ====

* urine abnormalities (leukocyturia, bacteriuria)
* imaging (voiding cystography, scintigraphy)

==== Therapy ====

* management of infections
* surgical correction of reflux
* treatment of CKD complications

=== '''Analgesic nephropathy''' ===
Results from chronic abuse of analgesics (historically phenacetin-containing drugs).

==== Features ====

* slowly progressive renal insufficiency
* hematuria
* renal colic (papillary necrosis)
* hypertension

==== Complications ====

* increased risk of urothelial carcinoma
* other manifestations (psychosomatic, bone, cardiovascular, hematological and gastrointestinal disorders).

Pathogenesis of Select Types of Poisoning

Mags — Thu, 30 Apr 2026 21:31:51 GMT

← Older revision		Revision as of 23:31, 30 April 2026
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	~~{{Under construction}}~~

	Poisoning is an acute pathological state caused by the effects of ingested, inhaled, or otherwise absorbed [[Toxicity, effects of noxious substances\|toxic substances]] on the body.		Poisoning is an acute pathological state caused by the effects of ingested, inhaled, or otherwise absorbed [[Toxicity, effects of noxious substances\|toxic substances]] on the body.

Line 242:		Line 240:
	N-acetylcysteine can be given orally or intravenously. Once in the body, it loses its acetyl group to become cysteine. In the production of glutathione, the formation of cysteine is the rate-limiting factor. Thus, supplementing with a cysteine precursor allows the body to rapidly replenish glutathione stores to bind the NAPQI before it can wreak havoc on the [[Hepatocyte\|hepatocytes]].<ref>Atkuri, K. R., Mantovani, J. J., Herzenberg, L. A., & Herzenberg, L. A. (2007). N-Acetylcysteine—a safe antidote for cysteine/glutathione deficiency. ''Current Opinion in Pharmacology'', ''7''(4), 355–359. <nowiki>https://doi.org/10.1016/j.coph.2007.04.005</nowiki></ref> In treating paracetamol poisoning, time is of the essence to save as much hepatic function as possible. It is ideal to treat within a few hours at most.		N-acetylcysteine can be given orally or intravenously. Once in the body, it loses its acetyl group to become cysteine. In the production of glutathione, the formation of cysteine is the rate-limiting factor. Thus, supplementing with a cysteine precursor allows the body to rapidly replenish glutathione stores to bind the NAPQI before it can wreak havoc on the [[Hepatocyte\|hepatocytes]].<ref>Atkuri, K. R., Mantovani, J. J., Herzenberg, L. A., & Herzenberg, L. A. (2007). N-Acetylcysteine—a safe antidote for cysteine/glutathione deficiency. ''Current Opinion in Pharmacology'', ''7''(4), 355–359. <nowiki>https://doi.org/10.1016/j.coph.2007.04.005</nowiki></ref> In treating paracetamol poisoning, time is of the essence to save as much hepatic function as possible. It is ideal to treat within a few hours at most.

	== Amanita Phalloides ==		== Amanita Phalloides (Death Cap) ==
			[[File:Amanita phalloides 172730215.jpg\|thumb\|Amanita Phalloides, the Death Cap mushroom]]
	~~=== Entry & Sources ===~~		The death cap mushroom is responsible for the vast majority of mushroom-related fatalities, and is considered the most poisonous mushroom on earth.

	=== Pathogenesis ===		=== Pathogenesis ===
			Death cap mushrooms contain an amatoxin called α-amanitin. This toxin is heat-stable, i.e. it is not degraded by cooking. Once one of these mushrooms is eaten, the amatoxin absorbed from the GI tract is taken up by the liver through [[portal circulation]]. In the hepatocytes, it non-covalently binds [[RNA polymerase II\|DNA-dependent RNA polymerase II]]. Without RNA polymerase II, no [[mRNA]] is produced, and subsequently, no proteins are produced. The liver cell eventually undergoes [[Apoptosis and Necrosis\|apoptosis or necrosis]].<ref name=":11">Kayes, T., & Ho, V. (2024). Amanita Phalloides-associated liver failure: Molecular mechanisms and management. ''International Journal of Molecular Sciences'', ''25''(23), 13028. <nowiki>https://doi.org/10.3390/ijms252313028</nowiki></ref>

	=== Symptoms ===		=== Symptoms ===
			The symptom progression of A. phalloides poisoning is peculiar: After a few hours and up to a day, the mushroom acts on the stomach lining, causing what appears to be severe gastroenteritis. This leads to massive fluid loss. A day or so later, GI symptoms subside in what the patient assumes is a complete recovery from potential food poisoning. Finally, fulminant liver failure develops, with all the classic symptoms:<blockquote>
			dramatic rise in transaminases and bilirubin associated with coagulopathy, hypoglycemia, acidosis, renal failure (potentially hepatorenal syndrome), and hepatic encephalopathy. Multi-organ failure, disseminated intravascular coagulation, rapid central nervous system deterioration, severe hemorrhagic manifestations, and death may occur within 1–3 weeks after ingestion.<ref name=":11" />
			</blockquote>

	=== Treatment ===		=== Treatment ===
			Upon suspicion of A. phalloides consumption, [[gastric lavage]] +/- activated charcoal should be provided. Silibinin is given as a hepatoprotective agent, along with N-acetylcysteine for its experimentally demonstrated protective/supportive effects. There is no real [[Antidotes in intoxications\|antidote]] to amatoxins, only supportive measures to give the patient better odds. In case the liver progresses to fulminant hepatic failure, liver [[transplantation]] may be the only remaining option.<ref name=":4" />

	== Links ==		== Links ==

Nonspecific Inflammatory Bowel Diseases - Crohn's disease, Ulcerative colitis

86.49.232.144 — Thu, 30 Apr 2026 21:27:53 GMT

New page

'''Crohn’s Disease'''

Crohn’s disease (colitis regionalis, ileitis terminalis) is a chronic inflammatory bowel disease. The inflammation can occur in any part of the digestive tract and has a segmental pattern—affected areas are separated by sections of healthy mucosa. The most affected region is the terminal ileum. The inflammation involves the entire thickness of the organ wall and is characterized by the presence of non-caseating epithelioid granulomas.

'''Epidemiology'''

Crohn’s disease occurs more often in younger people. The highest prevalence is in the 30–39 age group. About 10% of patients are diagnosed before the age of 17.

The average prevalence in adults is about 130 per 100,000, with an incidence of 5.6 per 100,000 inhabitants.

The incidence in children is increasing, reaching up to 9–10 per 100,000, especially in Northern Europe. The incidence in children in the Czech Republic is 6.2 per 100,000.

'''Risk Factors'''

First-degree relatives have a 10–35 times higher risk of developing the disease.

Genetic mutations.

High hygiene standards in childhood, smoking, early appendectomy, and nonsteroidal anti-inflammatory drugs (NSAIDs).

'''Etiopathogenesis'''

The cause of the disease is not yet known. It is likely a dysregulation of the immune response to common bacterial antigens. During this autoimmune reaction, transmural inflammation develops—meaning inflammation that affects the entire thickness of the intestinal wall and often extends to the mesentery. Epithelioid granulomas, ulcerations, and fissures form within the intestinal wall. Intramural and intraperitoneal abscesses or fistulas (especially in the anal region) are also commonly observed. Due to long-term inflammation, narrowing of the intestine may occur as a result of tissue scarring (fibrotic strictures).

A characteristic feature of Crohn’s disease is segmental involvement of the gastrointestinal tract—alternating inflamed and unaffected sections (“skip lesions”). Commonly affected areas include the terminal ileum and the ascending colon, but any part of the gastrointestinal tract can be involved.

'''Pathological Image'''

The entire intestinal wall is affected, and the inflammation is segmental or multisegmental. Typically, affected sections alternate with unaffected ones (in contrast to ulcerative colitis).

'''Macroscopical Image'''

Macroscopically, there is thickening of the intestinal wall and mesentery. Regional lymph nodes are often enlarged. The mucosa is hypertrophic and edematous. The appearance is often compared to cobblestones—elongated aphthous ulcers over lymphoid follicles surrounded by unaffected mucosa, raised openings of fistulas, and pseudopolyps. Involvement of the serosa leads to adhesions, within which fistulas may form. As the disease progresses, fibroproduction occurs, leading to the development of stenoses.

'''Microscopical Image'''

Under the microscope, mucosal edema with polymorphonuclear infiltration is observed, followed by fibroproduction with the formation of tuberculoid granulomas (composed of epithelioid cells and Langhans-type giant cells, which—unlike in tuberculosis—do not undergo caseation) in the submucosa, subserosa, and regional lymph nodes.

'''Clinical Image'''

Like all autoimmune diseases, Crohn’s disease manifests in multiple systems. The typical presentation is in the digestive tract, but the eyes, skin and mucous membranes, liver, pancreas, and kidneys can also be affected, and blood homeostasis is often impaired.

'''Intestinal Manifestation'''

Common symptoms include abdominal pain and chronic diarrhea (rarely with blood). Around the anus, fissures, perianal abscesses, fistulas, and skin tags (anal folds—skin outgrowths at the junction of the anal opening and the skin) may occur.

'''Extraintestinal manifestations'''

Extraintestinal symptoms occur in more than 40% of patients. They often precede intestinal symptoms by several years. These are mostly nonspecific symptoms such as recurrent fever, anorexia, weight loss, and delayed growth, especially in children. The main systems that may be affected include:

* '''Skeletal system:''' growth impairment and osteoporosis (proinflammatory cytokines suppress growth, reduce IGF-1 production, and stimulate bone resorption; also influenced by insufficient energy intake, malabsorption, loss of proteins and trace elements in stool, and long-term corticosteroid therapy).
* '''Skin and mucous membranes:''' aphthous stomatitis, gingivitis, cheilitis granulomatosis, erythema nodosum on the lower legs, and pyoderma gangrenosum.
* '''Eyes:''' iritis, uveitis, episcleritis; rare in children; corticosteroid therapy may induce cataracts and glaucoma.
* '''Liver and pancreas:''' primary sclerosing cholangitis, gallstones; pancreatitis following treatment with azathioprine or mesalazine.
* '''Vascular system:''' hypercoagulable state (thrombocytosis, increased levels of fibrin, factors V and VII, decreased antithrombin), which may lead to deep vein thrombosis, pulmonary embolism, or stroke.
* '''Kidneys and urinary tract:''' fistulas and urinary stones.

'''Complications'''

The inflammation often spreads to surrounding tissues and forms fistulas (i.e., channels connecting the inflamed area with another site). Fistulas may be:

* '''Internal:''' enteroenteric, enterocolic, enterovesical, rectovaginal
* '''External:''' involving the abdominal wall or perineum

Other complications include:

* Formation of abscesses, which may be interloop, pelvic, retroperitoneal, or hepatic
* Intestinal stenosis, which is dangerous due to the risk of ileus
* Perianal fissures
* Intestinal perforation and its complications, such as peritonitis
* Massive bleeding
* Toxic megacolon
* Malignant transformation (development of carcinoma)

----'''Diagnosis'''

The diagnosis of the disease is classically based on medical history, physical examination, and laboratory and imaging methods. Patients often report abdominal pain, chronic diarrhea, growth delay (which may precede gastrointestinal symptoms), and recurrent fevers. During physical examination, typical changes of the skin and mucous membranes, as well as the anal and genital regions (fistulas, skin tags), may be found, and an abdominal mass may be palpable.
----'''Laboratory diagnostics'''

* Markers of acute and chronic inflammation: CRP, ESR, albumin levels, complete blood count – anemia, leukocytosis, thrombocytosis
* Antibodies against ''Saccharomyces cerevisiae'' (ASCA), positive in more than 50% of patients
* Parameters of liver, kidney, and pancreatic function – due to the risk of involvement of these organs
* Fecal calprotectin – an indicator of mucosal inflammation (a leukocyte cytosolic protein released after activation or lysis of leukocytes)
* Occult blood in stool

----'''Imaging methods'''

* '''Ultrasound:''' thickening of the intestinal wall and detection of abdominal abscesses
* '''MR enterography''', MRI of the pelvic floor
* Previously used '''enterography (enteroclysis):''' contrast (barium suspension) administered into the duodenum under X-ray control, followed by methylcellulose solution
* '''Irrigography:''' X-ray examination of the colon after rectal administration of contrast (used when endoscopy is not possible)
* '''Fistulography:''' contrast injection into a fistula under X-ray control
* '''CT scan:''' diagnosis of abdominal abscesses

----'''Endoscopic examination'''

* '''Colonoscopy:''' allows both macroscopic and microscopic examination of the mucosa (aphthous lesions, ulcerations, cobblestone appearance, strictures); in children, performed under general anesthesia
* '''Gastroscopy'''
* '''Capsule endoscopy:''' a miniature digital camera in a plastic capsule (11 × 26 mm) that enables examination of the small intestine (the segment between gastroscopy and colonoscopy); can be used from about 6 years of age, and in small children it may be inserted into the duodenum via gastroscopy.

'''Therapy'''

'''Pharmacological therapy'''

* '''Corticosteroids''' – used to induce remission during acute inflammation; remission is achieved in about 85% of patients
** Systemic: Prednisone 1–2 mg/kg/day (maximum 60 mg/day) for 2–4 weeks, followed by gradual tapering
** Alternatively, locally acting Budesonide – less effective but with fewer side effects
* '''Immunomodulatory drugs''' – used to maintain remission without corticosteroids
** Thiopurines – require monitoring of blood count, liver function tests, and amylase; risk of allergic reactions
** Methotrexate
* '''Antibiotics''' – Ciprofloxacin, Metronidazole
* '''5-aminosalicylates''' – Sulfasalazine, Mesalazine (more effective in ulcerative colitis) [5]

----'''Targeted therapy (biological agents)'''

* Infliximab (Remicade) – chimeric monoclonal antibody (human + mouse) against TNF-α; used in patients resistant to conventional therapy
* Adalimumab (Humira) – fully human monoclonal antibody [5]

----'''Nutritional therapy'''

* Remission can be induced by '''exclusive enteral nutrition''' – a complete elemental diet based on amino acids for 4–6 weeks reduces inflammation (especially in children), but relapse after discontinuation is common [5]

----'''Surgical therapy'''

* There is a risk of recurrence even after successful surgery
* Indicated in complications (perforation, bleeding, fistulas, abscesses, strictures, significant growth retardation, tumors) [5]

'''Procedures include:'''

* Resection with anastomoses or stomas
* Strictureplasty and balloon dilation of stenoses
* Abscess drainage
* Fistulotomy

'''Principles:'''

* Resections should be as limited as possible (due to the likelihood of repeated surgeries; at least 60 cm of small intestine should be preserved)
* Strictureplasty is preferred over resection when feasible
* End-to-end anastomoses
* Stoma formation in acute conditions or when rectal reconstruction is not possible
* Avoid creating a pouch in rectal reconstruction

'''Types of operations:'''

* Segmental resection of the small and large intestine
* Ileocecal resection with ileo-ascending anastomosis
* Right hemicolectomy with ileo-transverse anastomosis
* Subtotal colectomy with ileorectal anastomosis
* Proctocolectomy with ileostomy
* Abdominoperineal resection with colostomy

If the rectum is not affected, it is preferable to preserve it even with a permanent ileostomy (to protect pelvic nerve plexuses and maintain sexual function), although this requires regular monitoring for inflammatory lesions.

Appendectomy carries a risk of fistula formation, but it is often performed so that appendicitis can be excluded as a cause of symptoms in case of recurrence.
----'''Prevention'''

There is no known prevention, as the cause of the autoimmune dysregulation is not yet fully understood.

'''ULCERATIVE COLITIS'''

Ulcerative colitis (idiopathic proctocolitis, ''proctocolitis idiopathica'', ICD-10: K51) is a rare autoimmune type of inflammation of the digestive tract. It is a hemorrhagic–purulent to ulcerative inflammation affecting the mucosa and submucosa of the rectum and the adjacent part of the colon (proctocolitis), or sometimes the entire colon (pancolitis); the small intestine is never involved. About 20% of patients are diagnosed before the age of 20.

'''Epidemiology'''

* Prevalence: 150 per 100,000 inhabitants
* 19% of patients are children under 18 years of age – pediatric prevalence: 29 per 100,000; pediatric incidence: 1–3 per 100,000
* The incidence has not been increasing in recent years (unlike Crohn’s disease)
* The average age of patients is 11 years

'''Etiopathogenesis'''

The cause is unknown. One of the most likely theories is a dysregulation of the immune response to common bacterial antigens. The inflammation affects only the rectum and colon, to varying extents. In children, pancolitis is common. The inflammation is continuous, and the distal parts of the colon are usually more severely affected.

'''Pathological findings'''

Only the mucosa and submucosa are affected. Unlike Crohn's disease, the involvement is continuous. Macroscopically, there is contraction of the affected segment; the mucosa is hypertrophic and edematous with numerous ulcers with raised margins, the serosa is shiny, and the mesocolon is not thickened. Microscopically, crypt abscesses are present (dilated crypts filled with polymorphonuclear cells; their breakdown leads to detachment of the mucosa and ulceration).
----'''Clinical presentation'''

'''Gastrointestinal symptoms'''

* Bloody diarrhea
* Lower abdominal pain associated with defecation
* Tenesmus (painful urge to defecate with a persistent feeling of incomplete evacuation)

Based on localization, two main syndromes are distinguished:

* '''Rectal syndrome:''' tenesmus with passage of small amounts of stool or mucus with blood
* '''Colitic syndrome:''' crampy abdominal pain with watery diarrhea containing blood and mucus, and albumin loss

----'''Extraintestinal manifestations'''

These are significantly less frequent than in Crohn's disease. They include:

* Arthralgia
* Erythema nodosum
* Pyoderma gangrenosum

----'''Complications'''

* Iridocyclitis (affects about 1% of patients)
* Glaucoma and cataracts due to corticosteroid therapy
* Primary sclerosing cholangitis – may precede manifestations of ulcerative colitis
* “Overlap syndrome” with autoimmune hepatitis, primary sclerosing cholangitis, and ulcerative colitis
* Thromboembolic complications
* Toxic megacolon (risk factors: anticholinergics, opioids, irrigography, colonoscopy)
* Colorectal carcinoma (after 10 years in 2% of patients, after 50 years in 40%) – prevention with 5-ASA and folic acid

----'''Diagnosis'''

* '''Medical history:''' chronic diarrhea, rectal bleeding, localized abdominal pain, fatigue, weight loss
* '''Physical examination:''' pallor, tender resistance in the left lower abdomen
* '''Laboratory findings:''' mildly to moderately elevated inflammatory markers, anemia
* '''pANCA antibodies:''' positive in about 70%
* Other parameters similar to those in Crohn's disease

'''Endoscopy'''

* Method of choice; both upper and lower endoscopy are performed (to differentiate from Crohn's disease)

'''Imaging'''

* '''Ultrasound:''' thickened intestinal wall
* '''Irrigography:''' used only when strictures cannot be passed endoscopically; shows loss of colonic haustration, pseudopolyps, strictures
* '''Leukocyte scintigraphy:''' not routinely used (only nonspecific detection of inflammation)

----'''Therapy'''

'''Main goals:''' induction and maintenance of remission, prevention of complications

'''Pharmacological therapy'''

* '''5-aminosalicylates:''' Sulfasalazine, Mesalazine – inhibit arachidonic acid metabolism and have mild anti-inflammatory effects
* '''Corticosteroids:''' locally acting Budesonide or systemic Prednisone
* '''Immunomodulators:''' Azathioprine, 6-mercaptopurine
* '''Cyclosporine A:''' used in corticosteroid-resistant cases
* '''Tacrolimus:''' an immunosuppressant from the macrolide group

'''Targeted (biological) therapy'''

* Infliximab (Remicade) – chimeric monoclonal antibody against TNF-α

'''Probiotics'''

* ''E. coli'' Nissle – in adults with mild disease, has an effect comparable to mesalazine

'''Nutritional therapy'''

* Enteral nutrition is less effective than in Crohn's disease

----'''Surgical therapy'''

'''Urgent indications:''' perforation, bleeding, endotoxemic shock, toxic megacolon

* Subtotal colectomy with ileostomy and closure of the rectal stump (Hartmann procedure) or exteriorization as a mucous fistula (Mikulicz procedure)

'''Elective surgery:''' indicated in failure of conservative treatment, mucosal dysplasia or carcinoma, strictures, or extraintestinal manifestations

* Total proctocolectomy with ileostomy or ileoanal anastomosis with a pouch (J, S, or W pouch)
* The pouch serves as a stool reservoir, eliminating the need for a permanent ileostomy

----'''Supportive therapy'''

* Psychological care

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Pathophysiology of the Spleen

86.49.232.144 — Thu, 30 Apr 2026 21:26:00 GMT

new article

New page

'''Pathophysiology of the Spleen: Splenomegaly, Hypersplenism, and Asplenia'''

'''Introduction and Epidemiology'''

The spleen is a vital lymphoid organ involved in hematologic filtration and immune surveillance. Disorders of the spleen most commonly manifest as splenomegaly, hypersplenism, or functional impairment such as asplenia. These conditions are rarely primary diseases but instead reflect underlying systemic pathology. Splenomegaly is frequently encountered in clinical practice, particularly in association with chronic liver disease, hematologic malignancies, hemolytic anemias, and infectious diseases such as infectious mononucleosis and malaria. Hypersplenism commonly accompanies splenomegaly and contributes to peripheral cytopenias. In contrast, asplenia may be either anatomical, following splenectomy or congenital absence, or functional, as seen in conditions such as sickle cell disease. Although relatively less common, asplenia carries significant clinical importance due to the associated risk of overwhelming infections.
----'''Risk Factors'''

The development of splenic pathology is closely tied to systemic conditions. Chronic liver disease leading to portal hypertension is a major risk factor for splenic enlargement due to venous congestion. Hematologic disorders, including hereditary hemolytic anemias such as thalassemia and hereditary spherocytosis, predispose to splenic hyperactivity and enlargement. Infectious diseases, particularly viral, bacterial, and parasitic infections, stimulate immune-mediated splenic hyperplasia. Infiltrative disorders such as storage diseases and malignancies also contribute significantly. Asplenia most commonly results from surgical removal of the spleen following trauma or hematologic disease, while functional asplenia frequently arises in sickle cell disease due to repeated splenic infarctions leading to progressive fibrosis and atrophy.
----'''Etiopathogenesis'''

The pathophysiology of splenomegaly is multifactorial and reflects several underlying mechanisms. Congestive splenomegaly arises in the context of portal hypertension, where increased venous pressure leads to blood pooling within the splenic sinusoids. Hyperplastic splenomegaly results from increased immune activity, with proliferation of lymphoid tissue in response to infections or immune stimulation. Infiltrative splenomegaly occurs when abnormal cells or substances, such as malignant cells or storage material, accumulate within the splenic parenchyma. In hemolytic conditions, the spleen enlarges due to increased destruction of abnormal or damaged erythrocytes.

Hypersplenism represents a functional consequence of splenic enlargement and is characterized by increased sequestration and destruction of blood cells. The enlarged spleen retains and prematurely removes erythrocytes, leukocytes, and platelets from circulation, leading to cytopenias despite normal or increased bone marrow activity. This process reflects both mechanical pooling and enhanced phagocytic activity of splenic macrophages.

Asplenia, whether anatomical or functional, results in the loss of splenic immune and filtration functions. The spleen plays a crucial role in clearing opsonized pathogens, particularly encapsulated bacteria, and in removing abnormal erythrocytes. In functional asplenia, these processes are impaired despite the presence of splenic tissue. Following splenectomy, the complete absence of splenic function leads to immunological deficits, including reduced production of IgM memory B cells and impaired phagocytic clearance.
----'''Pathological Features'''

'''Macroscopical Appearance'''

Macroscopically, splenomegaly is characterized by an enlarged organ that may reach several times its normal size. The spleen often appears dark red or bluish due to congestion, with a tense and sometimes fragile capsule. In severe cases, particularly in hematologic disorders, the spleen may become massively enlarged and prone to rupture. Areas of infarction may be visible as pale, wedge-shaped lesions.

'''Microscopical Appearance'''

Microscopically, the most prominent finding in splenomegaly is expansion of the red pulp, often accompanied by congestion of splenic sinusoids. Increased numbers of macrophages are present, reflecting heightened phagocytic activity. In hypersplenism, there is evidence of active destruction of blood cells within the red pulp. In cases of asplenia or hyposplenism, peripheral blood smears reveal characteristic Howell–Jolly bodies, representing nuclear remnants in erythrocytes that would normally be removed by a functioning spleen.

'''Clinical Presentation'''

Clinically, splenomegaly may be asymptomatic or present with a sensation of fullness or discomfort in the left upper quadrant of the abdomen. Enlargement of the spleen can lead to early satiety due to compression of the stomach. Hypersplenism manifests through symptoms related to cytopenias, including fatigue from anemia, increased susceptibility to infections due to leukopenia, and bleeding tendencies associated with thrombocytopenia. In contrast, patients with asplenia are particularly vulnerable to severe and rapidly progressing infections, often presenting with sepsis.

'''Complications'''

The complications of splenic disorders are significant and potentially life-threatening. Splenomegaly increases the risk of splenic rupture, particularly following trauma, which can result in acute intra-abdominal hemorrhage. Hypersplenism leads to pancytopenia, predisposing patients to infection, anemia-related complications, and bleeding. Following splenectomy, patients are at risk of overwhelming post-splenectomy infection, a rapidly progressive and often fatal condition most commonly caused by encapsulated bacteria. Additionally, splenectomy is associated with an increased risk of thromboembolic events due to elevated platelet counts. Functional or anatomical asplenia similarly predisposes individuals to severe infections, underscoring the spleen’s essential role in host defense.
----'''Diagnosis'''

The diagnosis of splenic disorders involves a combination of clinical examination, laboratory testing, and imaging studies. Physical examination may reveal a palpable spleen, although significant enlargement is typically required before it becomes detectable. Laboratory findings in hypersplenism include cytopenias affecting one or more cell lines, while peripheral blood smear in asplenic patients may demonstrate Howell–Jolly bodies. Imaging modalities such as ultrasound provide an initial assessment of splenic size, while computed tomography offers more precise evaluation and can identify complications such as infarction or rupture.
----'''Therapy'''

Management of splenic disorders is primarily directed at the underlying cause. Infectious etiologies require appropriate antimicrobial therapy, while hematologic conditions may necessitate transfusions, immunosuppressive therapy, or disease-specific treatments. Splenectomy is considered in cases of severe hypersplenism, symptomatic massive splenomegaly, or certain hemolytic anemias. In selected cases, partial splenectomy or splenic artery embolization may be performed to preserve some degree of splenic function while alleviating symptoms.
----'''Prevention'''

Preventive strategies are particularly important in patients with asplenia or those undergoing splenectomy. Vaccination against encapsulated organisms, including pneumococcus, meningococcus, and ''Haemophilus influenzae'', is essential. Prophylactic antibiotics may be indicated in certain populations, especially children. Patients should be educated about the importance of seeking prompt medical attention for febrile illnesses. In individuals with splenomegaly, avoidance of activities that increase the risk of abdominal trauma is recommended to prevent splenic rupture.

Renal Endocrine Disorders and Renal Osteopathy

Zainapatel — Thu, 30 Apr 2026 21:17:30 GMT

i made a new article

New page

'''Renal Endocrine Disorders and Renal Osteopathy'''

'''Introduction and Epidemiology'''

The kidneys function not only as excretory organs but also as critical endocrine regulators, producing hormones such as erythropoietin, renin, and calcitriol. Disruption of these endocrine functions is a hallmark of chronic kidney disease (CKD) and contributes to a wide range of systemic complications. Among the most significant of these is renal osteopathy, also referred to as renal osteodystrophy, which represents the skeletal manifestation of chronic disturbances in mineral and bone metabolism.

Renal endocrine disorders are highly prevalent in patients with CKD, particularly in advanced stages. Disturbances of calcium, phosphate, parathyroid hormone (PTH), and vitamin D metabolism occur early in the course of renal impairment and progressively worsen as kidney function declines. Renal osteopathy is therefore most commonly observed in patients with long-standing CKD or end-stage renal disease (ESRD), especially those undergoing dialysis. With the global rise in CKD, driven largely by diabetes mellitus and hypertension, the burden of renal bone disease has increased substantially.
----'''Risk Factors'''

The primary risk factor for renal endocrine dysfunction is chronic kidney disease of any etiology. Conditions such as diabetes mellitus and hypertension are the leading causes worldwide. Additional contributors include prolonged dialysis, inadequate vitamin D intake, limited sunlight exposure, and dietary imbalances of calcium and phosphate. Certain medications, including phosphate-containing drugs and corticosteroids, may exacerbate mineral disturbances. Age, genetic predisposition, and poor adherence to treatment regimens also influence disease severity. In children, growth impairment may be a prominent feature due to disturbances in bone metabolism.
----'''Etiopathogenesis'''

The pathogenesis of renal endocrine disorders is complex and involves interrelated disturbances in mineral metabolism and hormonal regulation. As renal function declines, phosphate excretion is impaired, leading to hyperphosphatemia. Elevated serum phosphate levels, in turn, stimulate the secretion of parathyroid hormone, resulting in secondary hyperparathyroidism. Simultaneously, the diseased kidney loses its ability to convert vitamin D into its active form, calcitriol, leading to reduced intestinal calcium absorption and hypocalcemia.

These changes create a cycle of persistent parathyroid stimulation, promoting bone resorption and high-turnover bone disease, known as osteitis fibrosa cystica. In contrast, excessive suppression of PTH, often due to overtreatment, can lead to adynamic bone disease characterized by low bone turnover. Another manifestation, osteomalacia, arises from defective bone mineralization due to vitamin D deficiency or aluminum toxicity.

Renal osteopathy thus encompasses a spectrum of skeletal abnormalities resulting from chronic disturbances in calcium-phosphate balance, hormonal dysregulation, and impaired bone remodeling.

'''Pathological Features'''

'''Macroscopical Appearance'''

Macroscopically, bones affected by renal osteopathy may appear deformed, fragile, and prone to fractures. In advanced cases, skeletal deformities such as bowing of long bones and changes in the skull, often described as a “salt-and-pepper” appearance on imaging, may be observed. The cortical bone may be thinned, and overall bone mass is often reduced.
----'''Microscopical Appearance'''

Microscopically, renal osteopathy demonstrates a range of findings depending on the dominant pathology. In high-turnover disease, there is increased osteoclastic bone resorption and fibrous tissue replacement, sometimes forming so-called brown tumors. Osteomalacia is characterized by the accumulation of unmineralized osteoid. In adynamic bone disease, there is reduced cellular activity with minimal bone formation or resorption. These histological patterns reflect the underlying hormonal imbalances and altered bone metabolism.
----'''Clinical Presentation'''

Clinically, patients with renal osteopathy may present with bone pain, muscle weakness, and skeletal deformities. Fractures may occur with minimal trauma due to reduced bone strength. In children, growth retardation and skeletal abnormalities are common. Soft tissue and vascular calcifications may develop as a result of disordered mineral metabolism, contributing to cardiovascular complications. In severe cases, calciphylaxis may occur, characterized by painful skin lesions and tissue necrosis.
----'''Complications'''

Renal endocrine disorders and osteopathy are associated with numerous complications. Skeletal complications include fractures, deformities, and chronic pain, which significantly impair quality of life. Secondary hyperparathyroidism may lead to parathyroid hyperplasia and, in some cases, autonomous hormone production. Vascular and soft tissue calcifications increase the risk of cardiovascular disease, which is a leading cause of mortality in CKD patients. Calciphylaxis represents a particularly severe and life-threatening complication. Additionally, anemia due to reduced erythropoietin production and disturbances in blood pressure regulation due to altered renin secretion are important systemic consequences.
----'''Diagnosis'''

The diagnosis of renal endocrine disorders relies on a combination of laboratory and imaging studies. Biochemical evaluation typically reveals abnormalities in serum calcium, phosphate, parathyroid hormone, and vitamin D levels. Elevated alkaline phosphatase may indicate increased bone turnover. Imaging studies, including X-rays and bone densitometry, can detect structural changes and reduced bone density. In selected cases, bone biopsy remains the gold standard for distinguishing between different types of renal osteodystrophy. Assessment of kidney function, including glomerular filtration rate, is essential for staging CKD and guiding management.
----'''Therapy'''

Management focuses on correcting the underlying metabolic disturbances and slowing disease progression. Control of phosphate levels is achieved through dietary restriction and the use of phosphate binders. Vitamin D supplementation, particularly active forms such as calcitriol, is used to address deficiency and suppress secondary hyperparathyroidism. Calcimimetic agents may be employed to reduce parathyroid hormone levels. In severe cases, surgical removal of the parathyroid glands (parathyroidectomy) may be necessary.

Optimization of dialysis and, when feasible, kidney transplantation are important therapeutic strategies, as transplantation can restore endocrine function and improve bone metabolism. Pain management and fracture prevention are also key components of care.
----'''Prevention'''

Preventive measures center on early detection and management of chronic kidney disease. Tight control of underlying conditions such as diabetes and hypertension is essential. Monitoring of mineral metabolism parameters allows for timely intervention before severe bone disease develops. Adequate dietary management, appropriate supplementation with vitamin D, and adherence to prescribed therapies play crucial roles. In patients receiving dialysis or following transplantation, regular follow-up is necessary to prevent progression and complications.

Pathogenesis of Select Types of Poisoning

Mags — Thu, 30 Apr 2026 21:01:14 GMT

finished paracetamol

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Urolithiasis, disorders of the urinary tract and bladder

Himnesh — Thu, 30 Apr 2026 19:38:31 GMT

everything

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Urolithiasis is the presence of concretions (stones) in the urinary tract – in the renal pelvis (nephrolithiasis), ureter (ureterolithiasis), urinary bladder (cystolithiasis), or urethra (urethrolithiasis), or stone-forming substances in the renal parenchyma (nephrocalcinosis). In our population, the most common type is calcium oxalate stones.
----

== '''Pathogenesis''' ==
'''Crystal formation and aggregation'''

Main causes include:

* Supersaturation of urine with stone-forming substances (Ca²⁺, urates, oxalate), promoted by reduced urine output (low diuresis)
* Urinary stasis (obstructive uropathy)
* Changes in urine pH (including bacteria that break down urea – ''Proteus, Pseudomonas, Klebsiella'' → struvite lithiasis)
* Deficiency of crystallization and aggregation inhibitors (citrates, pyrophosphates, Mg²⁺, glycoproteins)
* Certain drugs (sulfonamides, antacids)

'''Cystolithiasis''' develops due to chronic urinary retention in subvesical obstruction or neurogenic bladder.
----

== '''Types of stones''' ==

* '''Radiopaque (visible on X-ray):'''
** Calcium oxalate
** Calcium phosphate
** Struvite (MgNH₄PO₄)
** Cystine stones
* '''Radiolucent (not visible on X-ray):'''
** Uric acid stones
** Xanthine stones

----

== '''Clinical presentation''' ==
Urolithiasis may be asymptomatic (non-moving stones).

Depending on location:

* '''Nephrolithiasis:''' dull kidney pain (tenderness, positive tapping pain), possibly colic if urine outflow is blocked
* '''Ureterolithiasis:''' renal colic with autonomic symptoms; pain radiates depending on location (back, inner thigh)
* '''Cystolithiasis:''' suprapubic pain, frequent urination (pollakisuria), urgency

Often accompanied by hematuria and complications such as infections (pyelonephritis, cystitis)
----

== '''Complications''' ==

* Obstruction → renal colic, hydronephrosis
* Infection → up to urosepsis
* Bleeding
* Renal failure (especially if bilateral obstruction)

----

== '''Diagnostics''' ==
Urine:

* Sediment examination
* Chemical analysis (including cystine)
* pH, density
* Culture (may be negative in complete obstruction)

Blood:

* Ca²⁺, phosphate, uric acid
* Acid-base status (to rule out RTA – renal tubular acidosis)

Stone analysis:

* Chemical analysis
* Mineralography (polarized microscopy, X-ray diffraction)

Imaging:

* Ultrasound – stones + dilation of urinary tract, acoustic shadow
* X-ray (KUB, excretory urography)
* Cystography (for bladder stones)
* Cystoscopy
* Spiral CT
* DMSA scan (functional kidney study)

Metabolic disorders associated:

* Hypercalcemia → hyperparathyroidism
* Hypercalciuria (absorptive or renal type)
* Hyperoxaluria (fat malabsorption: chronic pancreatitis, obstructive jaundice)
* Hyperuricosuria (myeloproliferative diseases, purine disorders, chemotherapy)
* Hypercystinuria (genetic transport defect)
* Hypocitraturia (chronic diarrhea, thiazides)

----

== '''Metabolic evaluation''' ==
Serum:

* Urea, creatinine, uric acid
* Electrolytes (Na⁺, K⁺, Ca²⁺, Mg²⁺, Cl⁻, phosphate)
* Glucose, proteins, liver tests, lipids

24-hour urine:

* Volume, pH
* Excretion of phosphate, uric acid, creatinine
* Electrolytes and oxalates, citrates, sulfates

Calculations:

* Creatinine clearance
* Uric acid clearance
* Ca²⁺/creatinine ratio, Ca²⁺/Mg²⁺ ratio
* Proteinuria

Diet testing:

* Low-calcium diet followed by 1000 mg oral calcium tablets

----

== '''Differential diagnosis''' ==

* Acute abdomen
* Biliary colic
* Gynecological conditions
* Tumor, UTI, coagulopathy (hematuria causes)
* Urothelial tumor (filling defect)
* Phlebolith (on imaging)

----

== '''Treatment''' ==

=== Acute renal colic: ===

* Analgesics
* Spasmolytics
* NSAIDs (e.g., indomethacin)
* Hydration
* Urinary diversion (if infection or sepsis)

=== Chronic urolithiasis: ===

* Endoscopic procedures
* Instrumentation:
** Nephrostomy
** Ureteral stenting and stone extraction
** Cystoscopic extraction or fragmentation
* Extracorporeal shock wave lithotripsy (ESWL)
* Open surgery (rare ~1%): lithotomy, nephrotomy, nephrectomy

Stone extraction tools:

* Forceps
* Zeiss loop
* Dormia basket

Stone fragmentation:

* Mechanical
* Ultrasound
* Electrohydraulic
* Laser

----

== '''Indications for lithotripsy''' ==

* Radiopaque stones <2 cm, soft composition, good anatomy and drainage
* <blockquote>2 cm or hard stones or poor anatomy → alternative methods</blockquote>
* Radiolucent stones → difficult targeting
* Small asymptomatic stones:
** ≤4 mm ureteral stones → conservative management

----

== '''Urine pH modification''' ==

* Uric acid stones → alkalinize urine (potassium/sodium citrate)
* Struvite stones → acidify urine

----

== '''Prevention (metaphylaxis)''' ==

* '''General:'''
** High fluid intake
** Reduced salt, protein, calcium intake
* '''Specific:'''
** Citrates
** Allopurinol (for hyperuricemia / urate stones)

== '''References / Related sections''' ==

=== '''Related articles''' ===

* [[Urolitiáza (pediatrie)]]
* [[Konkrementy]]
* [[Infekce močových cest]]
* [[Infekce močových cest/kazuistika]]
* [[Radiodiagnostické vyšetření vývodných cest močových]]

Pathogenesis of Select Types of Poisoning

Mags — Thu, 30 Apr 2026 18:44:48 GMT

methemoglobnemia treatment

← Older revision		Revision as of 20:44, 30 April 2026
Line 140:		Line 140:

	=== Symptoms ===		=== Symptoms ===
	The most identifiable clinical symptom of methemoglobinemia is a distinct '''blue-gray''' discoloration of the skin due to the lack of oxygenation. The greater the proportion of erythrocytes affected, the more blue the patient appears. The cyanosis also does not improve with oxygen therapy.<ref>Chui, J. S. W., Poon, W. T., Chan, K. C., Chan, A. Y. W., & Buckley, T. A. (2005). Nitrite-induced methaemoglobinaemia - aetiology, diagnosis and treatment. ''Anaesthesia'', ''60''(5), 496–500. <nowiki>https://doi.org/10.1111/j.1365-2044.2004.04076.x</nowiki></ref> As with most cases of poisoning, the symptoms are dose-dependent:~~<blockquote>~~		The most identifiable clinical symptom of methemoglobinemia is a distinct '''blue-gray''' discoloration of the skin due to the lack of oxygenation. The greater the proportion of erythrocytes affected, the more blue the patient appears. The [[cyanosis]] also does not improve with oxygen therapy.<ref name=":9">Chui, J. S. W., Poon, W. T., Chan, K. C., Chan, A. Y. W., & Buckley, T. A. (2005). Nitrite-induced methaemoglobinaemia - aetiology, diagnosis and treatment. ''Anaesthesia'', ''60''(5), 496–500. <nowiki>https://doi.org/10.1111/j.1365-2044.2004.04076.x</nowiki></ref> As with most cases of poisoning, the symptoms are dose-dependent:
	Those with very mild methemoglobinemia might not have any symptoms at all, or might appear a little pale and feel tired. Moderate-to-severe poisoning is associated with cyanosis (blueness of the skin), confusion, loss of consciousness, seizures, abnormal heart rhythms, and death.<ref name=":8" />		Those with very mild methemoglobinemia might not have any symptoms at all, or might appear a little pale and feel tired. Moderate-to-severe poisoning is associated with cyanosis (blueness of the skin), confusion, loss of consciousness, seizures, abnormal heart rhythms, and death.<ref name=":8" />
	~~</blockquote>~~

	=== Treatment ===		=== Treatment ===
			Firstly, any remaining nitrites in the gastrointestinal symptoms need to be absorbed with activated charcoal before the methemoglobinemia can progress. Next, assessment of the severity is made: In patients with <30% methemoglobin and in asymptomatic patients, this supportive treatment is usually enough.<ref name=":9" /> Otherwise, treatment protocols call for [[methylene blue]] intravenously or, when methylene blue is contraindicated (e.g., [[Glucose-6-phosphate dehydrogenase deficiency\|G6PD deficiency]]), [[vitamin C]].
			[[File:Methylene blue.png\|thumb\|417x417px\|Methylene blue mechanism]]

			==== ''Methylene blue'' ====
			In methemoglobinemia, ferrous iron is oxidized to ferric iron. The goal of treatment is to reduce ferric iron back to ferrous iron. Methylene blue is an oxidizing agent, which is of no immediate use. However, NADPH from the pentose phosphate pathway reduces methylene blue into leukomethylene blue. Leukomethylene blue can now reduce ferric iron back into ferrous iron.<ref>Mak, R. S. P., & Liebelt, E. L. (2021). Methylene blue an antidote for methemoglobinemia and beyond. In ''Lippincott Williams & Wilkins''. Wolters Kluwer Health. <nowiki>https://cme.lww.com/ovidfiles/00006565-202109000-00009.pdf</nowiki></ref>

			In patients with glucose-6-phosphate dehydrogenase deficiency, NADPH production in the pentose phosphate pathway is disrupted or absent. Therefore, methylene blue treatment may not have any therapeutic effects.

			==== ''Vitamin C'' ====
			Vitamin C is an [[Antioxidant protection of the human body\|antioxidant]], and generally acts directly as a reducing agent. In symptomatic methemoglobinemia, is needed intravenously in large quantities to be of therapeutic benefit, but it does not need to undergo any reactions like methylene blue to be effective.

	== Methanol & Ethylene Glycol ==		== Methanol & Ethylene Glycol ==

File:Methylene blue.png

Mags — Thu, 30 Apr 2026 18:35:25 GMT

Mags uploaded File:Methylene blue.png

New page

The mechanism of methylene blue therapy in methemoglobinemia

Pathogenesis of Select Types of Poisoning

Mags — Thu, 30 Apr 2026 18:00:50 GMT

almost finished nitrites

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Multiple myeloma and other plasma cell-derived proliferative syndromes (MGUS, Wahlstrom’s hypergammaglobinemia)

Simon Katzemich — Thu, 30 Apr 2026 15:24:18 GMT

Created page with "= A. Multiple Myeloma<ref>https://flexikon.doccheck.com/de/Multiples_Myelom<nowiki/>https://www.mayoclinic.org/diseases-conditions/multiple-myeloma/symptoms-causes/syc-20353378<nowiki/>https://emedicine.medscape.com/article/204369-overview<nowiki/>https://themmrf.org/multiple-myeloma/</ref> = Multiple Myeloma (MM), formally recognized by the WHO as plasma cell myeloma, represents a malignant transformation within the B-cell lineage. It is characterized by the monoclonal..."

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= A. Multiple Myeloma<ref>https://flexikon.doccheck.com/de/Multiples_Myelom<nowiki/>https://www.mayoclinic.org/diseases-conditions/multiple-myeloma/symptoms-causes/syc-20353378<nowiki/>https://emedicine.medscape.com/article/204369-overview<nowiki/>https://themmrf.org/multiple-myeloma/</ref> =
Multiple Myeloma (MM), formally recognized by the WHO as plasma cell myeloma, represents a malignant transformation within the B-cell lineage. It is characterized by the monoclonal proliferation of plasma cells within the bone marrow, which subsequently overproduce dysfunctional immunoglobulins or fragments known as paraproteins. As the most common malignant neoplasm of the bone marrow, it is a condition that requires a sophisticated understanding of both hematology and systemic organ pathology.

=== The Biological Progression and Etiology ===
The disease rarely appears as an acute event; rather, it typically follows a biological continuum. It often begins as Monoclonal Gammopathy of Undetermined Significance (MGUS), an asymptomatic state that becomes more common with advancing age. This may progress to Smouldering Multiple Myeloma (SMM), a dormant, intermediate phase, before finally manifesting as active, symptomatic disease.

While the exact etiology remains multifactorial, the genetic architecture of MM is remarkably complex. Approximately half of all patients exhibit a hyperdiploid karyotype involving trisomies of various chromosomes. In non-hyperdiploid forms, specific chromosomal translocations at the IgH-locus, such as t(11;14) or t(4;14), are common markers that heavily influence both the disease trajectory and therapeutic stratification. Environmental factors, including exposure to industrial chemicals, radiation, or chronic infections, are suspected triggers, though a definitive causal link is often difficult to isolate, even in cases where MM is recognized as an occupational disease.

=== Pathophysiological Impact: The Bone-Kidney Axis ===
The malignancy exerts its influence primarily through two channels: displacement and structural destruction. As the clonal plasma cells expand within the marrow, they suppress healthy hematopoietic stem cells, leading to anemia and, in advanced stages, pancytopenia.

Simultaneously, the disease creates a hostile environment for bone metabolism. Myeloma cells express high levels of RANKL, which overstimulates osteoclasts (bone-resorbing cells) while inhibiting osteoblasts (bone-forming cells). This uncoupling of bone remodeling leads to the characteristic osteolytic lesions that cause debilitating pain and spontaneous fractures. Furthermore, the secretion of paraproteins, whether complete immunoglobulins (predominantly IgG or IgA) or free light chains, creates a heavy burden on the kidneys. These proteins can accumulate, leading to renal insufficiency, amyloidosis, and a classic triad of clinical complications: hypercalcemia, renal failure, and systemic amyloid accumulation.

=== Clinical Presentation and Diagnostic Synthesis ===
Diagnosing Multiple Myeloma requires a high index of suspicion, as symptoms are often non-specific. Clinicians utilize the CRAB criteria (Calcium elevation, Renal failure, Anemia, Bone lesions) as a framework for identifying organ damage. Patients may present with generalized fatigue, severe skeletal pain, or recurring infections due to the loss of functional antibody production.

The diagnostic pathway has modernized significantly. While serum electrophoresis and immunofixation remain essential for identifying the "M-gradient," the measurement of free light chains via nephelometric or turbidimetric methods is now critical. Clinicians must remember that standard urine test strips cannot detect Bence-Jones proteinuria; specialized laboratory assays are required. Radiologically, the antiquated "Pariser Schema" of X-rays has been largely superseded by whole-body low-dose CT, which offers far superior sensitivity for osteolyses. Conversely, skeletal scintigraphy is frequently avoided, as the lack of osteoblastic activity often results in false-negative findings. A definitive diagnosis is ultimately secured via bone marrow biopsy, where a plasma cell fraction exceeding 10% serves as a primary diagnostic benchmark.

=== Therapeutic Strategies and Management ===
Treatment for Multiple Myeloma is multimodal and requires interdisciplinary coordination. The primary objective is not merely to treat the cancer, but to manage symptoms, prevent organ damage, and extend progression-free survival.

For younger, eligible patients, the gold standard remains autologous stem cell transplantation following a myeloablative induction regimen, such as the VRD-schema (Bortezomib, Lenalidomide, and Dexamethasone). For patients who are not candidates for transplantation, often due to age or comorbidities, the therapeutic landscape is highly diverse. Modern regimens integrate proteasome inhibitors (e.g., Bortezomib, Carfilzomib), immunomodulators (e.g., Lenalidomide), and monoclonal antibodies (e.g., Daratumumab, Isatuximab). In cases of refractory disease, innovative therapies like CAR-T cell treatments (e.g., Idecabtagen-Vicleucel) are increasingly utilized to achieve remission.

Supportive care is equally critical. Monthly administration of bisphosphonates (such as Zoledronat) or Denosumab is standard practice to protect the bone structure and mitigate the risk of lytic lesions, usually paired with calcium and Vitamin D supplementation.

=== Prognosis ===
While Multiple Myeloma remains fundamentally incurable as of 2026, the prognosis has improved markedly with the advent of targeted therapies. The Revised International Staging System (R-ISS), which integrates Beta-2-microglobulin, albumin, LDH, and cytogenetic data, allows for nuanced risk stratification. Despite the heterogeneity of the disease, modern interventions have turned what was once a rapidly fatal condition into a chronic, manageable illness for many, though the long-term outlook remains heavily dependent on individual disease biology and response to treatment

= B. Monoclonal Gammopathy of Undetermined Significance (MGUS)<ref>https://flexikon.doccheck.com/de/Monoklonale_Gammopathie_unklarer_Signifikanz<nowiki/>https://www.mayoclinic.org/diseases-conditions/mgus/symptoms-causes/syc-20352362<nowiki/>https://www.hopkinsmedicine.org/health/conditions-and-diseases/monoclonal-gammopathies</ref> =
Monoclonal Gammopathy of Undetermined Significance (MGUS) is defined by the presence of monoclonal immunoglobulins (paraproteins) in the serum in the absence of the diagnostic criteria for active Multiple Myeloma or other related malignancies. While MGUS is fundamentally a pre-malignant or asymptomatic state, it is a significant clinical diagnosis due to its potential to evolve into more serious pathologies.

=== Clinical Significance: Beyond the "Undetermined" ===
While MGUS is defined by the absence of myeloma-defining symptoms, the condition can be associated with secondary health issues, a state often referred to as Monoclonal Gammopathy with Clinical Significance (MGCS). In these cases, the monoclonal proteins, even without reaching the threshold of frank malignancy, can cause organ or systemic damage:

* '''Peripheral Neuropathy:''' Particularly common in IgM-MGUS, often involving antibodies directed against myelin-associated glycoprotein (MAG).
* '''Renal Impact:''' Known as Monoclonal Gammopathy of Renal Significance (MGRS), where light-chain proteins cause direct renal impairment.
* '''AL-Amyloidosis:''' Deposition of monoclonal light chains in tissues.
* '''POEMS Syndrome:''' A constellation including polyneuropathy, edema, and sclerotic bone lesions (often associated with Lambda-type MGUS).
* '''Systemic Inflammatory Syndromes:''' Including the Schnitzler Syndrome (fever, urticaria, arthralgia) and other comorbidities like osteoporosis, recurrent infections, hemolysis, and cryoglobulinemia.

=== Etiology and Epidemiology ===
The precise origin of MGUS remains largely unknown. However, researchers have identified links between IgM-MGUS and the somatic MYD88-L265P mutation, which is also characteristic of Waldenström macroglobulinemia. Other potential contributing factors include autoimmune diseases, chronic inflammation, obesity, and environmental exposures such as pesticides or ionizing radiation.

Epidemiologically, MGUS is an age-related phenomenon, with a prevalence of up to 3% in the population over the age of 50. It is statistically more frequent in men than in women.

=== Progression Risks and Prognosis ===
MGUS is not static; it carries a distinct risk of progression into active malignancies, such as Multiple Myeloma, Waldenström macroglobulinemia, or Non-Hodgkin Lymphoma.

'''Progression Rate:''' For heavy-chain MGUS, the risk of developing Multiple Myeloma is approximately 1% per year.

'''Risk Stratification:''' The probability of progression can be estimated based on the presence of three risk factors:

# Monoclonal protein concentration >15 g/l.
# An abnormal free light chain (FLC) ratio (normal range: 0.26 to 1.65).
# Non-IgG type MGUS.

'''Prognostic Impact:''' Patients exhibiting all three risk factors are classified as "High-Risk," with a progression probability exceeding 50% after 20 years, compared to only 5% for those without these risk factors. Conversely, light-chain MGUS shows a lower progression risk of approximately 0.3% per year.

Beyond hematologic malignancy, MGUS is associated with a higher incidence of non-hematological solid tumors and an increased risk (2–3 times) for venous thromboembolism and pulmonary embolism. Overall, MGUS is linked to an increased rate of mortality compared to the general population.

=== Diagnostic Criteria ===
The identification of an M-gradient in serum protein electrophoresis is often incidental. To confirm an MGUS diagnosis, the following criteria must be met:

* '''Monoclonal protein:''' <30 g/l (Serum).
* '''Bone marrow:''' Clonal plasma cells <10%.
* '''Absence of symptoms:''' No signs of Multiple Myeloma or other lymphomas (specifically excluding CRAB-SLiM criteria).

For the '''light-chain type''', additional criteria apply:

* Urinary protein excretion <500 mg per 24 hours.
* Demonstrable abnormality in the free light chain ratio.

=== Management: The "Watchful Waiting" Strategy ===
Unlike Multiple Myeloma or MGRS, MGUS itself does not require active chemotherapy. The standard of care is "Watchful Waiting."

* '''Follow-up Schedule:''' The initial assessment occurs at 3 and 6 months post-diagnosis.
* '''Monitoring:''' If laboratory parameters remain stable after these initial 6 months, further routine monitoring is often unnecessary for low-risk patients. However, high-risk patients require regular follow-up every 6 to 24 months to detect any early signs of progression to a condition requiring active treatment.

= C. Waldenström’s Macroglobulinemia<ref>https://flexikon.doccheck.com/de/Morbus_Waldenstr%C3%B6m<nowiki/>https://www.onkopedia.com/de/onkopedia/guidelines/morbus-waldenstroem-lymphoplasmozytisches-lymphom/@@guideline/html/index.html<nowiki/>https://iwmf.com/wp-content/uploads/2024/01/German-Germany_IWMF-Essential-Information-Physician-Guide_v2-1.pdf</ref> =
Waldenström’s Macroglobulinemia (WM), classified as an indolent non-Hodgkin lymphoma (NHL), is defined by the malignant clonal proliferation of lymphoplasmacytic cells within the bone marrow. These cells produce large quantities of monoclonal IgM immunoglobulins (paraproteins), leading to systemic complications. While the clinical course shares features with Multiple Myeloma, WM is biologically and therapeutically distinct.

=== Pathogenesis and Genetic Architecture ===
The molecular profile of WM is highly specific, which is increasingly relevant for personalized therapy.

* '''Genetic Drivers:''' Over 90% of patients exhibit the MYD88-L265P mutation, which drives the activation of the NF-κB pathway via IRAK and BTK (Bruton’s tyrosine kinase). Additionally, mutations in the CXCR4 gene are found in approximately 25–30% of cases.
* '''Risk Factors:''' While the exact cause is idiopathic, a strong familial component exists; first-degree relatives of patients have a significantly increased risk of developing WM or other lymphoproliferative disorders. Chronic inflammation, autoimmune phenomena, and a history of MGUS (Monoclonal Gammopathy of Undetermined Significance) are also associated with increased risk.
* Pathophysiology: The Impact of IgM

The hallmark of WM is the accumulation of large IgM molecules in the blood and the infiltration of the bone marrow, spleen, liver, and lymph nodes.

* '''Hyperviscosity Syndrome:''' Because IgM molecules are physically large pentamers, high serum concentrations (typically >5 g/dl) lead to increased blood viscosity, resulting in perfusion disturbances, visual impairments, neurological symptoms, and an increased risk of thrombosis.
* '''Organ Infiltration:''' Unlike myeloma, WM rarely causes bone destruction or hypercalcemia. However, it leads to systemic organ enlargement, including splenomegaly, hepatomegaly, and lymphadenopathy.
* '''Renal Sparing:''' Because IgM molecules are too large to be effectively excreted by the kidneys, renal failure, a common complication in myeloma, is rare in WM.
* '''Autoimmune Phenomena:''' Monoclonal IgM can act as an autoantibody, potentially causing cryoglobulinemia (e.g., Raynaud syndrome), anti-MAG (myelin-associated glycoprotein) peripheral neuropathy, or autoimmune hemolytic anemia.

=== Clinical Presentation ===
Symptoms often evolve insidiously. Common presentations include:

* '''Constitutional:''' Unexplained fatigue, fever, night sweats, and weight loss (B-symptoms).
* '''Hematologic:''' Normochromic, normocytic anemia (often the result of marrow infiltration), and occasionally neutropenia or thrombocytopenia.
* '''Hyperviscosity complications:''' Dizziness, ataxia, visual disturbances, or hearing loss.
* '''Physical signs:''' Palpable enlargement of the liver, spleen, or lymph nodes.

=== Diagnosis and Staging ===
A definitive diagnosis requires a synthesis of laboratory data and tissue biopsy:

* '''Bone Marrow:''' Biopsy is mandatory to confirm the infiltration of lymphoplasmacytic cells.
* '''Laboratory Analysis:''' Key findings include an elevated IgM spike in serum protein electrophoresis, elevated Beta-2-microglobulin, and signs of hyperviscosity (e.g., elevated ESR). The blood smear often shows "rouleaux formation" (stack-of-coins appearance of red blood cells).
* '''Molecular Testing:''' Assessing MYD88 and CXCR4 mutation status is critical, as it informs the efficacy of specific targeted therapies like BTK inhibitors.
* '''Staging:''' Because bone marrow involvement is an intrinsic criterion for the disease, WM is classified as Ann Arbor Stage IV by definition. The IPSSWM (International Prognostic Scoring System for WM) remains the standard for assessing prognosis based on age, hemoglobin, platelets, Beta-2-microglobulin, and IgM levels.

=== Therapeutic Strategies ===
As WM is considered incurable, the overarching management principle is "Watchful Waiting" for asymptomatic patients. Treatment is indicated only when symptoms emerge or when there is a high risk of hyperviscosity (IgM > 60 g/dl).

* '''Hyperviscosity Emergency:''' The immediate therapy of choice is plasmapheresis, which provides rapid, albeit temporary, relief.
* '''Systemic Therapy for Fit Patients:''' The standard approach combines chemotherapy with the anti-CD20 antibody Rituximab (e.g., R-Bendamustine or DCR—Dexamethasone, Cyclophosphamide, Rituximab). ''Note: Rituximab monotherapy in patients with high IgM levels carries the risk of a "flare phenomenon," where IgM levels temporarily rise, worsening hyperviscosity; these patients may require preliminary plasmapheresis.''
* '''BTK Inhibitors:''' For patients who are not candidates for chemo-immunotherapy or in the relapsed/refractory setting, BTK inhibitors (e.g., Ibrutinib, Zanubrutinib) are highly effective, particularly in MYD88-mutated cases.
* '''Prognosis:''' The prognosis has improved substantially in recent years, with a 5-year survival rate of approximately 80%.

=== Follow-Up and Management of Complications ===
Therapy response is evaluated using criteria ranging from "Complete Remission" (CR) to "Progressive Disease" (PD), noting that clinical response can sometimes lag months behind molecular or biochemical improvements. Follow-up is required every 3 months initially, transitioning to every 6–12 months after the third year. Specific complications, such as peripheral neuropathy (anti-MAG associated) or amyloidosis, require targeted, individualized management, often involving proteasome inhibitors like Bortezomib.

== D. Sources ==
[https://flexikon.doccheck.com/de/Morbus_Waldenstr%C3%B6mhttps://www.onkopedia.com/de/onkopedia/guidelines/morbus-waldenstroem-lymphoplasmozytisches-lymphom/@@guideline/html/index.htmlhttps://iwmf.com/wp-content/uploads/2024/01/German-Germany_IWMF-Essential-Information-Physician-Guide_v2-1.pdf https://flexikon.doccheck.com/de]

[https://flexikon.doccheck.com/de/Morbus_Waldenstr%C3%B6mhttps://www.onkopedia.com/de/onkopedia/guidelines/morbus-waldenstroem-lymphoplasmozytisches-lymphom/@@guideline/html/index.htmlhttps://iwmf.com/wp-content/uploads/2024/01/German-Germany_IWMF-Essential-Information-Physician-Guide_v2-1.pdf Morbus_Waldenstr%C3%B6mhttps://www.onkopedia.com/de/onkopedia/guidelines/morbus-waldenstroem-lymphoplasmozytisches-lymphom/@@guideline/html/index.html]

[https://flexikon.doccheck.com/de/Morbus_Waldenstr%C3%B6mhttps://www.onkopedia.com/de/onkopedia/guidelines/morbus-waldenstroem-lymphoplasmozytisches-lymphom/@@guideline/html/index.htmlhttps://iwmf.com/wp-content/uploads/2024/01/German-Germany_IWMF-Essential-Information-Physician-Guide_v2-1.pdf https://iwmf.com/wp-content/uploads/2024/01/German-Germany_IWMF-Essential-Information-Physician-Guide_v2-1.pdf]

https://flexikon.doccheck.com/de/Monoklonale_Gammopathie_unklarer_Signifikanz

https://www.mayoclinic.org/diseases-conditions/mgus/symptoms-causes/syc-20352362<nowiki/>https://www.hopkinsmedicine.org/health/conditions-and-diseases/monoclonal-gammopathies

https://flexikon.doccheck.com/de/Multiples_Myelom
https://www.mayoclinic.org/diseases-conditions/multiple-myeloma/symptoms-causes/syc-20353378<nowiki/>https://emedicine.medscape.com/article/204369-overview<nowiki/>https://themmrf.org/multiple-myeloma/

Pathogenesis of Select Types of Poisoning

Mags — Thu, 30 Apr 2026 15:10:24 GMT

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	=== Symptoms ===		=== Symptoms ===
	The symptoms of acute organophosphate poisoning are divided into two groups, nicotinic and muscarinic, based on the receptor causing the symptom:~~<blockquote>~~

			The symptoms of acute organophosphate poisoning are divided into two groups, nicotinic and muscarinic, based on the receptor causing the symptom:
	Muscarinic cholinergic symptoms: Salivation, lacrimation, urination, defecation, vomiting, pinpoint pupils (miosis), bronchorrhea and wheezing, bradycardia		Muscarinic cholinergic symptoms: Salivation, lacrimation, urination, defecation, vomiting, pinpoint pupils (miosis), bronchorrhea and wheezing, bradycardia
			Nicotinic cholinergic symptoms: Mydriasis, tachycardia, weakness and fasciculations, sweating, abdominal pain
	Nicotinic cholinergic symptoms: Mydriasis, tachycardia, weakness and fasciculations, sweating, abdominal pain

	Of these manifestations, muscle fasciculations and weakness are typical. Respiratory findings include rhonchi, wheezing, and hypoxia, which may be severe. Most patients have bradycardia and, if poisoning is severe, hypotension. Central nervous system toxicity is common, sometimes with seizures and excitability and often with lethargy and coma. Pancreatitis is possible, and organophosphates may cause arrhythmias such as heart block and QTc interval prolongation.<ref name=":6" />		Of these manifestations, muscle fasciculations and weakness are typical. Respiratory findings include rhonchi, wheezing, and hypoxia, which may be severe. Most patients have bradycardia and, if poisoning is severe, hypotension. Central nervous system toxicity is common, sometimes with seizures and excitability and often with lethargy and coma. Pancreatitis is possible, and organophosphates may cause arrhythmias such as heart block and QTc interval prolongation.<ref name=":6" />
	~~</blockquote>~~Students often remember the most important symptoms of muscarinic overactivation with the following mnemonic:		Students often remember the most important symptoms of muscarinic overactivation with the following mnemonic:

	'''DUMBBELS''' = '''D'''efecation, '''U'''rination, '''M'''iosis, '''B'''ronchorrhea/Bronchospasm, '''B'''radycardia, '''E'''mesis, '''L'''acrimation, '''S'''alivation.		'''DUMBBELS''' = '''D'''efecation, '''U'''rination, '''M'''iosis, '''B'''ronchorrhea/Bronchospasm, '''B'''radycardia, '''E'''mesis, '''L'''acrimation, '''S'''alivation.

The principle of negative feedback in endocrinology, Examples of glandular and receptor disorders

Simon Katzemich — Thu, 30 Apr 2026 14:07:22 GMT

Created page with "== A. The princinple of negative feedback in endocrinology<ref>Constanzo, 2018 https://flexikon.doccheck.com/de/R%C3%BCckkoppelung</ref> == Negative feedback is the cornerstone of homeostasis, the process by which virtually all organ systems in the body maintain stability. At its core, negative feedback is a self-correcting mechanism: when a physiological variable deviates from its "normal" range, the body activates processes to restore balance. Once that balance is ach..."

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== A. The princinple of negative feedback in endocrinology<ref>Constanzo, 2018

https://flexikon.doccheck.com/de/R%C3%BCckkoppelung</ref> ==
Negative feedback is the cornerstone of homeostasis, the process by which virtually all organ systems in the body maintain stability. At its core, negative feedback is a self-correcting mechanism: when a physiological variable deviates from its "normal" range, the body activates processes to restore balance. Once that balance is achieved, those activating mechanisms are switched off.

=== Negative Feedback in the Endocrine System ===
In the endocrine system, negative feedback operates on a principle of inhibition: the physiological action of a hormone eventually limits its own further secretion. This often involves a multi-tiered hierarchy involving the hypothalamus, the anterior pituitary gland, and a peripheral endocrine gland (such as the testes or thyroid).

The standard communication chain looks like this:

* '''Hypothalamus:''' Secretes a "releasing hormone."
* '''Anterior Pituitary:''' Stimulated by the releasing hormone, it secretes a second hormone.
* '''Peripheral Gland:''' Stimulated by the pituitary hormone, it secretes the final peripheral hormone (e.g., testosterone), which acts on target tissues to create a physiological effect.

To prevent overproduction, these hormones "feed back" to inhibit the secretions of the pituitary and hypothalamus. Depending on where the feedback signal originates, we classify them into three loops:

* '''Long-loop feedback:''' The final peripheral hormone travels all the way back to inhibit the hypothalamic-pituitary axis.
* '''Short-loop feedback:''' The anterior pituitary hormone travels back to inhibit the hypothalamus.
* '''Ultrashort-loop feedback:''' The hypothalamic hormone inhibits its own further secretion (e.g., growth hormone–releasing hormone inhibiting itself).

Ultimately, the net result is simple: if hormone levels are perceived as adequate or high, further secretion is inhibited. If levels are inadequate or low, secretion is stimulated.

=== Regulating Metabolism: The Insulin Example ===
Not all negative feedback loops require the hypothalamic-pituitary axis. The regulation of blood glucose is an excellent example of a direct metabolic feedback loop:

* When blood glucose levels rise, the pancreas is triggered to secrete insulin.
* Insulin acts on the liver, muscles, and adipose tissue to absorb glucose, effectively lowering the blood glucose concentration back toward normal.
* Once the glucose level is sufficiently low, the signal for insulin secretion is removed, and the process turns off.

In every instance, whether it is controlling pressure, hormone levels, or blood sugar, the logic remains the same: the body monitors the "output" of a system to decide whether to turn the "input" up or down, ensuring that conditions remain stable regardless of external changes.

== B. Examples of glandular and receptor disorders<ref>https://flexikon.doccheck.com/de/R%C3%BCckkoppelung

https://flexikon.doccheck.com/de/Morbus_Basedow

https://flexikon.doccheck.com/de/Diabetes_insipidus

https://de.wikipedia.org/wiki/Diabetes_insipidus_renalis

https://www.netdoktor.de/krankheiten/diabetes-insipidus/</ref> ==

=== B1. Grave's disease ===
Grave's disease is a glandular autoimmune thyroidopathy that leads to hyperthyroidism. It is clinically recognized by the "Merseburg Triad": goiter (struma), exophthalmos (protruding eyes), and tachycardia. While it is a systemic autoimmune condition, its primary manifestation involves the overstimulation of the thyroid gland.

==== 1. Epidemiology and Etiology ====
Graves' disease predominantly affects women, who are five to eight times more likely to develop the condition than men, with an onset typically occurring after the age of 35.

The disease has a strong genetic component, specifically linked to the HLA-DR3 haplotype, and often shows familial clustering. It is also frequently associated with other autoimmune conditions, such as type 1 diabetes mellitus, Addison’s disease, and rheumatoid arthritis. While environmental triggers (such as viral infections) are suspected, their role as definitive triggers is still under scientific investigation.

==== 2. Pathophysiology: The Role of Autoantibodies ====
The disease is driven by the production of IgG-type autoantibodies known as TSH-receptor antibodies (TRAK). These antibodies target the TSH receptors on the thyroid follicular cells. By mimicking the natural action of TSH, they cause a continuous, unregulated stimulation of the thyroid, leading to:

* '''Hyperthyroidism:''' The follicular cells produce and secrete excessive T3 and T4.
* '''Goiter formation:''' Chronic growth stimulation of the thyroid tissue.
* '''TSH Suppression:''' Because the autoantibodies also bind to TSH receptors in the pituitary gland, the body incorrectly perceives high thyroid hormone levels, suppressing TSH production. Consequently, TSH levels are not a reliable standalone parameter for monitoring disease severity.

'''Extrathyroidal manifestations:''' Autoantibodies can also bind to receptors outside the thyroid. This is responsible for the endocrine orbitopathy (where cytotoxic antibodies target retro-orbital fibroblasts, leading to inflammation, swelling, and fibrosis) and, less commonly, pretibial myxedema.

==== 3. Clinical Presentation ====
Beyond the classic Merseburg Triad (present in about 50% of cases), patients typically present with symptoms of systemic hyperthyroidism:

* '''Metabolic:''' Weight loss despite increased appetite, heat intolerance (often with subfebrile temperatures), and hyperhidrosis (excessive sweating).
* '''Cardiac/Vascular:''' Tachycardia, cardiac arrhythmias (such as atrial fibrillation), and increased pulse pressure (> 60 mmHg).
* '''Neurological/Psychological:''' Fine tremor, psychomotor agitation, nervousness, and sleep disturbances.
* '''Other:''' Muscle weakness (myopathy), decreased bone density (osteoporosis), and potential menstrual cycle irregularities.

==== 4. Diagnostics ====
A diagnosis is reached by synthesizing clinical, laboratory, and imaging findings:

* '''Physical Exam:''' Auscultation may reveal a "bruit" or humming sound over the thyroid due to high vascularization (turbulent blood flow).
* '''Laboratory Tests:''' Elevated T3/T4, suppressed TSH, and positive TRAK are diagnostic. Elevated anti-Tg or anti-TPO antibodies may be present if there is an overlapping autoimmune thyroid component.
* '''Imaging/''' '''Sonography:''' Typically shows an enlarged, hypoechoic (dark), highly perfused thyroid ("vascular inferno").
* '''Scintigraphy:''' Shows diffuse, increased uptake of Technetium.

==== 5. Therapeutic Strategies ====
The primary goal of therapy is to achieve a euthyroid (normal) metabolic state.

===== Medical Management =====
Thyrostatic medication (first-line agents: Thiamazol or Carbimazole) is used to normalize T3/T4 levels. Once euthyroid, the dose is titrated to maintain stability. A trial of therapy usually lasts up to one year, aiming for spontaneous remission. If remission is not achieved, or if TRAK levels remain elevated after six months, a definitive therapy is recommended.

===== Definitive Therapy =====
Indicated for persistent, refractory, or recurrent cases, as well as severe endocrine orbitopathy:

* '''Radioiodine Therapy:''' Highly effective at achieving remission, though strictly contraindicated during pregnancy and breastfeeding.
* '''Surgery (Total Thyroidectomy):''' Preferred for large goiters or when a patient expresses a desire for pregnancy. Lifelong levothyroxine substitution is required post-surgery.

Note: Before any definitive therapy, the patient ''must'' be brought to a euthyroid state. Any intervention (surgery or radiation) that causes thyroid cell damage releases stored hormones, which can trigger a life-threatening thyrotoxic crisis if the patient is not stabilized first.

==== 6. Special Considerations: Pregnancy ====
Managing Graves' disease during pregnancy is high-risk.

* '''Planning:''' Pregnancy should ideally be avoided until remission is achieved.
* '''Risks:''' Uncontrolled hyperthyroidism poses severe risks, including pre-eclampsia, spontaneous abortion, intrauterine growth restriction, and fetal/neonatal tachycardia.
* '''Transplacental Transfer:''' Maternal TRAK antibodies can cross the placenta, potentially causing neonatal hyperthyroidism. Newborns require thyroid monitoring 14 days after birth.
* '''Medication:''' Propylthiouracil is preferred during the first trimester due to the potential teratogenicity of other thyrostatics. Discussion regarding switching to Thiamazol/Carbimazole after the 16th week is ongoing due to the hepatotoxic risk of Propylthiouracil.
* '''Definitive Treatment:''' Surgery is the preferred definitive treatment if required ''before'' pregnancy. Radioiodine is absolutely contraindicated.

=== B2. Diabetes Insipidus Renalis (Nephrogenic Diabetes Insipidus) ===
Diabetes insipidus renalis, also known as nephrogenic diabetes insipidus, is a condition characterized by the kidneys' inability to respond to the antidiuretic hormone (ADH/vasopressin). This results in profound polyuria (excessive urination), often ranging from 5 to 25 liters per day, and a secondary, compensatory state of extreme thirst known as polydipsia.

==== 1. Pathomechanism ====
The core issue in nephrogenic diabetes insipidus is a resistance to ADH within the renal system, rather than a failure of hormone production.

In a healthy kidney, ADH signals the cells of the distal tubules and collecting ducts to insert aquaporins (specialized water channels) into their membranes. This allows the body to reabsorb water back into the bloodstream, concentrating the urine. In nephrogenic diabetes insipidus, a defect, often involving the V2-receptor (AVPR2), prevents these aquaporins from functioning. Consequently, the kidneys remain impermeable to water regardless of how much ADH is present, leading to the excretion of massive amounts of highly dilute urine.

==== 2. Etiology and Causes ====
The failure of the renal tubules to respond to ADH can be triggered by several factors:

* '''Genetic Factors:''' X-linked genetic defects that impair receptor function.
* '''Chronic Renal Conditions:''' Niereninsuffizienz (kidney insufficiency) or pyelonephritis (kidney infection).
* '''Medications and Toxins:''' Certain drugs and toxic exposures can interfere with renal function and the signaling pathways required for water reabsorption.

==== 3. Clinical Symptoms ====
The condition is defined by a triad of clinical findings:

* '''Asthenuria:''' The kidneys' inability to concentrate urine, leading to very low urine osmolality.
* '''Polyuria:''' A high volume of dilute urine output.
* '''Polydipsia:''' Excessive fluid intake to compensate for the massive water loss.

Because of the need to urinate frequently, patients often experience significant nocturia, which leads to disrupted sleep patterns, chronic fatigue, and reduced daily energy levels.

==== 4. Diagnosis ====
Diagnosing nephrogenic diabetes insipidus requires distinguishing the kidney’s lack of response from other forms of water-regulation issues.

* '''Copeptin Testing:''' This is a highly reliable diagnostic tool. Because Copeptin levels correlate directly with ADH levels, they provide a clear picture of renal response. In patients with nephrogenic diabetes insipidus, Copeptin levels are typically elevated (> 20 pmol/l), indicating that the body is producing the hormone but the kidneys are failing to respond to it.
* '''Differential Diagnosis:''' Clinicians must exclude other causes of high urine output, such as osmotic diuresis (associated with Diabetes mellitus) or primary polydipsia (compulsive water drinking).

==== 5. Therapeutic Strategies ====
Management is centered on mitigating the severe fluid and electrolyte imbalances caused by the condition. Treatment is often complex and requires careful titration.

* '''Thiazide Diuretics:''' While seemingly counterintuitive, these are often used because they promote sodium excretion. This reduces total blood volume, which triggers the kidney to increase the reabsorption of salt and water in the proximal tubules, indirectly helping to concentrate the urine.
* '''Prostaglandin Inhibitors (NSAIDs):''' Experimental and clinical evidence shows that prostaglandins inhibit the incorporation of aquaporin-2 into the collecting ducts. By administering NSAIDs (such as Ibuprofen or Indometacin), clinicians can block prostaglandin synthesis, thereby promoting the function of aquaporins and reducing urine output.

NSAID therapy requires extreme caution and is generally avoided in patients with existing renal insufficiency or in elderly patients, due to the potential for further kidney stress.

== C. Sources ==
Costanzo, Linda S. ''Physiology''. 6th ed., Elsevier, 2018.

https://flexikon.doccheck.com/de/R%C3%BCckkoppelung

https://flexikon.doccheck.com/de/Morbus_Basedow

https://flexikon.doccheck.com/de/Diabetes_insipidus

https://de.wikipedia.org/wiki/Diabetes_insipidus_renalis

https://www.netdoktor.de/krankheiten/diabetes-insipidus/

Immune mechanisms in the pathogenesis of diseases, disorders of immune tolerance

Arya Pawar — Thu, 30 Apr 2026 13:41:35 GMT

Creation of a article on the topic immune mechanisms and disorders of immune system

New page

The immune system protects the body against pathogens through highly regulated innate and adaptive responses. However, dysregulation of immune mechanisms can lead to tissue damage, hypersensitivity reactions, and autoimmune diseases. These pathological processes often arise from failure of immune tolerance or exaggerated immune responses.

== Key Definitions ==

* Immunity: The ability of the body to resist infections and eliminate foreign substances.
* Immune response: The reaction of immune cells and molecules against antigens.
* Antigen: Any substance capable of inducing an immune response.
* Self-antigen: Components of the body recognized as “self.”
* Immune tolerance: The ability of the immune system to avoid attacking self-antigens.
* Autoimmunity: Immune response directed against self-antigens.
* Hypersensitivity: Exaggerated or inappropriate immune response causing tissue damage.

== Hypersensitivity Reactions ==
There are four main types of hypersensitivity reactions, a mnemonic to remember them is

=== ACID ===
[[File:HSR.jpg|thumb]]
Allergic Reaction (type 1)

Cytotoxic Reaction (type 2)

Immune Complex Reaction (type 3)

Delayed Reaction (type 4)

=== Type I Hypersensitivity (Immediate) ===
Definition: IgE-mediated reaction occurring within minutes after antigen exposure

Mechanism:

* Allergen → activation of Th2 cells
* IL-4, IL-13 → IgE production
* IgE binds mast cells
* Re-exposure → cross-linking of IgE → mast cell degranulation
* Release of histamine, leukotrienes → vasodilation, bronchospasm

Morphology: Edema, eosinophils, mucus secretion

Clinical Examples:

* Anaphylaxis
* Bronchial asthma
* Allergic rhinitis (hay fever)

=== Type II Hypersensitivity (Antibody-Mediated) ===
Definition: IgG/IgM antibodies directed against cell surface or ECM antigens

Mechanisms:

# Opsonization → phagocytosis
# Complement-mediated lysis
# Inflammation via Fc/complement
# Receptor dysfunction (stimulating or blocking)

Morphology: Cell destruction, inflammation

Clinical Examples:

* Autoimmune hemolytic anemia
* Goodpasture syndrome
* Myasthenia gravis (receptor blockade)
* Graves disease (receptor stimulation)

=== Type III Hypersensitivity (Immune Complex) ===
Definition: Deposition of antigen-antibody complexes in tissues

Mechanism:

* Circulating Ag-Ab complexes → deposit in vessels
* Activate complement → neutrophil recruitment
* Enzymatic tissue damage

Morphology: Vasculitis, fibrinoid necrosis

Clinical Examples:

* Systemic lupus erythematosus (SLE)
* Poststreptococcal glomerulonephritis
* Serum sickness

=== Type IV Hypersensitivity (T-cell Mediated) ===
Definition: Delayed reaction mediated by T lymphocytes (not antibodies)

Mechanisms:

# CD4+ T cells → cytokines → macrophage activation
# CD8+ cytotoxic T cells → direct cell killing

Morphology: Mononuclear infiltrate, granulomas

Clinical Examples:

* Tuberculosis (granulomas)
* Contact dermatitis
* Type 1 diabetes mellitus

== Disorders of Immune Tolerance ==

=== Types of Immune Tolerance ===

# Central tolerance
#* Occurs in primary lymphoid organs (thymus, bone marrow)
#* Eliminates self-reactive T and B cells (negative selection)
# Peripheral tolerance
#* Occurs in peripheral tissues
#* Mechanisms:
#** Anergy (functional inactivation)
#** Suppression by regulatory T cells (Tregs)
#** Deletion via apoptosis

Failure of Tolerance Leads to:

* Autoimmune diseases
* Chronic inflammation
* Hypersensitivity reactions

== Autoimmune Diseases ==
Definition: Autoimmune diseases occur when the immune system attacks self-antigens due to breakdown of tolerance.

=== Pathogenesis ===

* Genetic susceptibility (HLA association)
* [[File:AI.jpg|thumb]]Environmental triggers (infections, drugs)
* Molecular mimicry (cross-reactivity)
* Loss of regulatory T-cell function

=== Types of Autoimmune Diseases ===
1. Organ-specific autoimmune diseases

* Affect a single organ

Examples:

* Type 1 diabetes mellitus
* Hashimoto thyroiditis
* Graves disease

2. Systemic autoimmune diseases

* Affect multiple organs

Examples:

* Systemic lupus erythematosus (SLE)
* Rheumatoid arthritis
* Systemic sclerosis

File:AI.jpg

Arya Pawar — Thu, 30 Apr 2026 13:40:43 GMT

Arya Pawar uploaded File:AI.jpg

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Hepatitis, toxic and metabolic liver damage, liver steatosis, steatohepatitis

Simon Katzemich — Thu, 30 Apr 2026 13:22:16 GMT

Created page with " == A. Hepatitis<ref>https://flexikon.doccheck.com/de/Hepatitis<nowiki/>https://my.clevelandclinic.org/health/diseases/17915-toxic-hepatitis<nowiki/>https://de.wikipedia.org/wiki/Hepatitis</ref> == '''Etymology:''' Derived from the Greek ''hepar'' (liver) '''Synonym:''' Inflammation of the liver === 1. Definition === Hepatitis refers to an inflammatory condition of the liver tissue. It can be triggered by infectious agents (primarily viral), toxins, immunological proce..."

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== A. Hepatitis<ref>https://flexikon.doccheck.com/de/Hepatitis<nowiki/>https://my.clevelandclinic.org/health/diseases/17915-toxic-hepatitis<nowiki/>https://de.wikipedia.org/wiki/Hepatitis</ref> ==
'''Etymology:''' Derived from the Greek ''hepar'' (liver)

'''Synonym:''' Inflammation of the liver

=== 1. Definition ===
Hepatitis refers to an inflammatory condition of the liver tissue. It can be triggered by infectious agents (primarily viral), toxins, immunological processes, or as a secondary result of other systemic diseases.

=== 2. Etiology ===
Hepatitis is triggered by an array of underlying causes. These are broadly categorized into the following groups:

'''Viral Hepatitis''' remains the most common form, characterized by infections from specific hepatotropic viruses:

* '''Hepatitis A (HAV):''' ''Picornaviridae'' family.
* '''Hepatitis B (HBV):''' ''Hepadnaviridae'' family.
* '''Hepatitis C (HCV):''' ''Flaviviridae'' family
* '''Hepatitis D (HDV):''' Requires co-infection with Hepatitis B.
* '''Hepatitis E (HEV):''' ''Hepeviridae'' family.
* '''Hepatitis G:''' An obsolete term for Human Pegivirus infection (''Flaviviridae'').

Beyond these, '''Viral "Bystander" Hepatitis''' may occur as a secondary complication of systemic infections, including various ''Herpesviridae'' (HSV, VZV, CMV, EBV), ''Picornaviridae'' (Coxsackie), and ''Flaviviridae'' (Yellow fever, Dengue).

'''Non-viral infections''' can also cause hepatitis, including bacterial pathogens (e.g., Leptospirosis, Brucellosis, Salmonellosis), various parasites (e.g., Malaria, Leishmaniasis, Amoebiasis, Echinococcosis, Schistosomiasis), and fungal infections such as ''Candida'' hepatitis.

Furthermore, '''Toxic Hepatitis''' arises from external insults, including alcohol (e.g., Zieve syndrome), fatty liver disease, radiation, chemical toxins (snake venom, mushroom poisons), and medication-induced damage (e.g., Paracetamol, Halothane, Isoniazid).

'''Secondary and Autoimmune causes''' encompass metabolic disorders like Hemochromatosis (iron) and Wilson’s disease (copper), as well as ischemia ("shock liver"), granulomatous diseases (Tuberculosis, Sarcoidosis), and various cholangitic conditions. Finally, autoimmune forms, such as Autoimmune Hepatitis (AIH), Primary Biliary Cholangitis (PBC), and Lupoid hepatitis, represent chronic inflammatory processes often of unclear origin.

=== 3. Clinical Presentation ===
Symptoms vary depending on the form of hepatitis. General signs typically include malaise, fatigue, exhaustion, and fever, often accompanied by gastrointestinal distress, specifically loss of appetite, nausea, dull pain in the right upper abdomen, and diarrhea. Arthralgia (joint pain) and transient rashes may also occur. In some instances, the condition may remain asymptomatic.

=== 4. Forms of Progression ===
The disease is classified by the duration and intensity of symptoms:

* '''Acute Hepatitis:''' Rapid onset, usually viral in origin.
* '''Chronic Hepatitis:''' A slow, insidious progression lasting longer than 6 months, often with non-specific symptoms.
* '''Fulminant Hepatitis:''' A highly acute, severe form (usually viral) characterized by liver necrosis and rapid-onset liver failure.

=== 5. Diagnostics ===
The diagnostic process begins with a physical examination, which may reveal hepatomegaly (enlarged liver) and potential induration. If jaundice is present, signs include yellowing of the skin and sclera.

Laboratory diagnostics focus on identifying elevated transaminases and, in icteric cases, increased cholestasis parameters. Physicians may also look for an accelerated erythrocyte sedimentation rate (ESR) or elevated C-reactive protein (CRP). In cases of fulminant hepatitis, a decline in liver synthetic function is confirmed by drops in cholinesterase, serum albumin, and prothrombin time (Quick’s value).

To determine the etiology, clinicians utilize serology (screening for markers like Anti-HAV, Anti-HBc, Anti-HCV, and HBs-Ag) and PCR to quantify viral load in HBV and HCV infections. If an autoimmune origin is suspected, a panel of specific antibodies is analyzed, including ANA, SMA, SLA, AMA, LKM, ANCA, and liver membrane antibodies.

=== 6. Therapy and Prognosis ===
Therapeutic strategies are entirely dependent on the underlying genesis and the stage of the disease. Treatment ranges from purely symptomatic care and monitoring to targeted antiviral regimens (e.g., interferons, nucleoside/nucleotide analogs, protease inhibitors) and immunosuppressive therapy. In cases of acute liver failure, a liver transplant may be the only life-saving option.

The prognosis is equally variable. While many acute forms achieve ''restitutio ad integrum'' (complete healing), chronic forms can lead to irreversible damage, such as liver cirrhosis or hepatocellular carcinoma (HCC).

=== 8. Prevention ===
Prevention is critical in the management of hepatitis.

==== 8.1. General Measures ====
Good personal hygiene is essential, particularly to reduce the risk of fecal-oral transmission (specifically for HAV and HEV). Blood and other bodily fluids (such as saliva and semen) from patients with acute HBV or HCV, as well as the stool of patients with Hepatitis A, must be considered infectious. Protective measures are recommended when handling such materials; however, patient isolation is rarely necessary. To minimize post-transfusion hepatitis, all blood donations are screened for HBsAg and anti-HCV, which has reduced the incidence of transfusion-related transmission to approximately 1:100,000 units.

==== 8.2. Immunoprophylaxis ====
This involves both active immunization (vaccination) and passive immunization. Vaccines are currently available for Hepatitis A and Hepatitis B.

This text has been translated and rephrased to flow as a cohesive clinical narrative while retaining all the specific medical data, diagnostic criteria, and classification details of the original.

== B. Toxic Hepatitis (Liver Toxicity)<ref>https://www.ncbi.nlm.nih.gov/books/NBK526106/<nowiki/>https://www.ucsfhealth.org/care/conditions/toxic-hepatitis<nowiki/>https://my.clevelandclinic.org/health/diseases/17915-toxic-hepatitis<nowiki/>https://www.mayoclinic.org/diseases-conditions/toxic-hepatitis/symptoms-causes/syc-20352202</ref> ==
Toxic hepatitis represents a liver injury caused not by viruses or genetics, but by the liver’s reaction to harmful external substances. As the body’s primary filter, the liver processes everything we consume, inhale, or touch. When it is overwhelmed by toxic agents, whether environmental chemicals, medications, or alcohol, it becomes inflamed. While this inflammation is a sign that the liver is struggling, persistent exposure can lead to severe, permanent damage.

=== Classifying Liver Toxicity ===
Toxic hepatitis is broadly understood through two lenses: how quickly it develops and what triggered it.

* '''Progression:''' Acute toxic hepatitis arrives suddenly, often with severe symptoms immediately following exposure. In contrast, chronic toxic hepatitis is insidious, potentially developing over weeks or months of exposure without obvious warning signs.
* '''Causation:''' Clinicians categorize these injuries based on the source: chemical-induced (industrial/environmental exposure), drug-induced (medication/supplement overload), or alcohol-induced (often exacerbated by recreational drug use).

=== Clinical Signs and Symptoms ===
The hallmark sign of liver toxicity is jaundice, where the skin and the whites of the eyes take on a yellow hue. However, the condition often manifests through a spectrum of symptoms, including:

* '''Gastrointestinal distress:''' Abdominal pain, nausea, and vomiting.
* '''Systemic fatigue:''' A general feeling of malaise, fever, and persistent exhaustion.
* '''Changes in excretion:''' Dark-colored urine and abdominal fluid buildup (ascites).
* '''Dermatological indicators:''' Some patients develop a "toxic hepatitis rash," characterized by splotchy areas or small purple dots, frequently accompanied by pruritus (intense itching).

=== Major Causes and Risk Factors ===
Toxic hepatitis is not contagious; it is a direct consequence of physiological overload. While individual susceptibility varies, meaning exposure does not guarantee illness in everyone, certain factors significantly heighten the risk.

'''Common triggers include:'''

* '''Drug and Supplement Overload:''' Many herbal supplements, prescription drugs, and NSAIDs carry risks. Acetaminophen (Tylenol) is a frequent culprit; adults should strictly avoid exceeding 4,000 mg in 24 hours or using the medication for more than 10 consecutive days.
* '''Vitamin A Toxicity:''' Daily intake exceeding 40,000 IU can reach toxic levels, causing significant liver strain.
* '''Environmental & Lifestyle Factors:''' Frequent contact with industrial solvents, a history of alcohol use disorder, or the use of recreational drugs all place the liver under immense pressure.
* '''Pre-existing Vulnerabilities:''' Individuals with underlying conditions, such as Hepatitis B/C, Hemochromatosis (iron overload), or Alpha-1 antitrypsin deficiency, are at a higher risk of developing toxic hepatitis upon exposure.

=== Diagnostic Approach ===
Because the symptoms of liver toxicity mimic many other conditions, diagnosis requires a methodical approach. Healthcare providers will begin with a thorough history of lifestyle and environmental exposure, followed by a physical examination.

To confirm the diagnosis, providers typically utilize:

* '''Blood Panels:''' A Comprehensive Metabolic Panel (CMP) and liver function tests, often supplemented by drug or alcohol screenings.
* '''Diagnostic Imaging:''' CT scans or MRIs to visualize liver integrity.
* '''Biopsy:''' In select cases, a liver biopsy may be necessary to assess the exact extent of tissue damage.

=== Management, Treatment, and Prognosis ===
The cornerstone of treating toxic hepatitis is the removal of the toxic agent. Once the liver is no longer under attack, it has a remarkable capacity to regenerate and replace damaged cells.

* '''The Recovery Process:''' Recovery time depends on the duration and severity of the injury. Mild cases may resolve within weeks or months, provided the patient adheres to strict lifestyle changes, such as ceasing alcohol intake, switching to safer medications, or using protective equipment in the workplace.
* '''The Clinical Outlook:''' While many cases are fully curable, advanced damage, such as cirrhosis, can lead to chronic liver failure, which may necessitate a liver transplant. Therefore, early intervention is critical.

=== Prevention and Liver Health ===
The most effective strategy for managing toxic hepatitis is prevention. Maintaining a healthy liver requires a proactive approach:

* '''Cautious Consumption:''' Always follow dosage instructions for over-the-counter medications and consult a healthcare provider before starting new herbal supplements.
* '''Environmental Safety:''' If your work involves chemicals, ensure proper safety gear is used and discuss protective protocols with your supervisor.
* '''Lifestyle Habits:''' Avoiding recreational drugs and limiting alcohol intake are vital. A "liver-friendly" diet, rich in fiber (whole grains, beans) and hydration, while low in sodium, fat, and sugar, can significantly reduce the burden on your liver's filtration systems.

== C. Steatotic Liver Disease (SLD)<ref>https://pmc.ncbi.nlm.nih.gov/articles/PMC4836586/<nowiki/>https://www.mayoclinic.org/diseases-conditions/fatty-liver-disease-masld/symptoms-causes/syc-20354567<nowiki/>https://my.clevelandclinic.org/health/diseases/15831-fatty-liver-disease</ref> ==
Your liver is a vital organ, performing hundreds of functions daily to keep your body running. Because of this, it is essential to monitor its health, particularly regarding the buildup of fat. Steatotic liver disease (SLD) is an umbrella term for conditions characterized by excess fat in the liver. A healthy liver contains a small amount of fat; however, it becomes a clinical concern when that fat accounts for more than 5% of the liver's total weight.

=== Understanding the Terminology ===
You may previously have known this condition as "fatty liver disease." In 2023, the medical community adopted the term Steatotic Liver Disease to more accurately reflect the underlying causes of the condition and to reduce the stigma associated with the older name. This new nomenclature helps differentiate between conditions caused by metabolic health, alcohol consumption, or other factors.

=== The Spectrum of SLD ===
Healthcare providers classify SLD based on the primary drivers of the disease:

* '''Alcohol-Related Liver Disease (ALD):''' Steatosis develops due to excessive alcohol intake, which overwhelms the liver's ability to regenerate its cells.
* '''Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD):''' Formerly called NAFLD, this occurs when fat builds up due to cardiometabolic risk factors, such as obesity, type 2 diabetes, high blood pressure, or lipid abnormalities. This category applies even if a patient consumes small amounts of alcohol (less than 140g/week for females; less than 210g/week for males).
* '''Metabolic-Associated Steatohepatitis (MASH):''' A more serious form of MASLD where the fat buildup progresses to actual inflammation and tissue damage (fibrosis).
* '''MetALD:''' This refers to patients who have both significant metabolic risk factors ''and'' consume alcohol above the thresholds mentioned above.
* '''Cryptogenic SLD:''' A diagnosis used when a clear cause for the fat buildup, whether metabolic or alcohol-related, cannot be identified.

=== Disease Progression: Why Early Detection Matters ===
In many cases, simple fat buildup does not interfere with normal liver function. However, if left unaddressed, the condition can progress through dangerous stages:

# '''Steatohepatitis (Inflammation):''' The liver becomes swollen, and tissue damage begins.
# '''Fibrosis:''' Chronic inflammation causes bands of scar tissue to form, which stiffens the liver.
# '''Cirrhosis:''' Extensive scarring replaces healthy tissue. At this stage, the liver may fail, leading to potentially fatal complications like liver cancer (specifically hepatocellular carcinoma, or HCC).

This progression highlights why it is vital to identify the cause of liver fat early. Because the liver has a remarkable ability to repair itself, intervention can stop, or sometimes even reverse, damage.

=== Symptoms and Risk Factors ===
SLD is often a "silent" condition, meaning it does not always cause symptoms. When symptoms do appear, they may include fatigue, general weakness, or a feeling of fullness in the upper right abdomen. By the time symptoms like jaundice, nausea, weight loss, or swelling (ascites/edema) appear, the disease has often progressed to cirrhosis.

'''Who is at risk?''' You are more likely to develop SLD if you have:

* '''Metabolic conditions:''' Type 2 diabetes, metabolic syndrome, obesity, or PCOS.
* '''Endocrine issues:''' Hypothyroidism, hypopituitarism, or hypogonadism.
* '''Other factors:''' Alcohol use disorder, sleep apnea, or a history of taking certain medications (e.g., steroids, tamoxifen, amiodarone, or diltiazem).

=== Diagnosis ===
Since early SLD rarely presents with symptoms, it is often discovered through routine blood work showing elevated liver enzymes. To confirm a diagnosis, your provider may use:

* '''Medical History & Physical Exam:''' Checking for an enlarged liver or signs of jaundice.
* '''Imaging:''' Ultrasound, CT scans, or MRIs. A specialized test called '''FibroScan®''' can quantify the amount of fat and scar tissue.
* '''Liver Biopsy:''' A tissue sample is the gold standard, particularly to distinguish between MASLD and MASH.

=== Management and Treatment ===
There is currently no single "magic pill" for SLD. Instead, treatment focuses on reversing the damage by managing the root causes:

* '''Lifestyle Changes:''' Weight loss (often aided by exercise and dietary changes) is crucial. Bariatric surgery may be an option for some patients.
* '''Metabolic Control:''' Managing diabetes, high cholesterol, and triglycerides through prescribed medication.
* '''Protective Measures:''' Avoiding alcohol entirely is recommended, even for non-alcohol-related cases. Getting vaccinated against Hepatitis A and B is also essential, as these viruses are dangerous to an already strained liver.
* '''Medication Adjustment:''' If a specific prescription is contributing to fat accumulation, your provider may adjust your dosage or switch your medication.

=== Outlook and Prevention ===
The prognosis for SLD is generally positive if caught early. Many people live a normal life expectancy, as the liver can heal if the metabolic risks are controlled and further damage is prevented. Prevention is straightforward: maintain a healthy weight, exercise regularly, limit alcohol, and manage conditions like diabetes proactively.

== D. Metabolic Dysfunction-associated Steatohepatitis (MASH)<ref>https://flexikon.doccheck.com/de/Fettleberhepatitis<nowiki/>https://my.clevelandclinic.org/health/diseases/15831-fatty-liver-disease</ref> ==
Metabolic Dysfunction-associated Steatohepatitis, commonly referred to as MASH, is a form of liver inflammation (hepatitis) that occurs in the context of hepatic steatosis (fatty liver). Crucially, this condition is driven by metabolic factors rather than alcohol consumption.

=== 1. Terminology and Definition ===
Historically, this condition was known as non-alcoholic steatohepatitis (NASH). However, in 2023, international hepatological societies, including those at the EASL Congress, formally updated the nomenclature to '''Metabolic Dysfunction-associated Steatohepatitis (MASH)'''. Consequently, what was previously called NASLD is now referred to as Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD).

=== 2. Epidemiology and Etiology ===
The exact etiology remains complex, but MASH is largely viewed as the hepatic manifestation of metabolic syndrome. Approximately 5% to 20% of cases of simple non-alcoholic fatty liver progress to MASH. It is important to note that other causes leading to hepatic steatosis are generally excluded from the MASH diagnosis (see Differential Diagnoses).

=== 3. Pathophysiology ===
As of 2026, the exact mechanisms underlying MASH are not yet fully understood. Current understanding suggests that the increasing accumulation of triglycerides within the liver parenchyma disrupts normal lipogenesis and beta-oxidation in hepatocytes. This process generates toxic lipids and induces oxidative stress, which triggers inflammation. As liver cells die, subsequent repair processes lead to the replacement of healthy parenchyma with low-quality fibrous connective tissue, a process known as fibrogenesis.

=== 4. Clinical Presentation and Complications ===
The clinical picture is highly variable. About 50% of patients remain completely asymptomatic. For those who do experience symptoms, common reports include reduced physical performance, general malaise, nausea, or a sensation of pressure in the right upper abdomen.

If left unmanaged, MASH can progress to liver fibrosis, cirrhosis, and the development of hepatocellular carcinoma (HCC). Indeed, it is estimated that over 50% of cryptogenic cirrhosis cases in industrialized nations are the result of underlying MASH.

=== 5. Diagnostic Approach ===
Diagnosing MASH involves a comprehensive assessment to rule out other causes and confirm metabolic factors:

* '''Anamnesis:''' Essential to rule out alcohol abuse and other potential drivers of steatohepatitis.
* '''Laboratory Tests:''' Typical findings include elevated liver enzymes (GOT, GPT, GGT) and ferritin. Metabolic syndrome screening (HbA1c, blood glucose, lipid profile) is also required.
* '''Imaging:''' Abdominal ultrasound can detect steatosis, fibrosis, or cirrhosis. Further assessment is often performed via liver elastography or MRI.
* '''Pathohistology:''' A liver biopsy may be used to distinguish MASH from simple fibrosis or cirrhosis, though it cannot microscopically differentiate MASH from alcoholic steatohepatitis. Because liver punctures carry a 0.1% mortality risk and potential for bleeding, they are used selectively.

'''Diagnostic Criteria:'''

# Evidence of hepatic steatosis (via imaging or histology).
# Exclusion of secondary steatosis (based on medical history).
# Exclusion of alcoholic origin (based on history; potentially supplemented by serum CDT and urine ethyl glucuronide testing).

=== 6. Histological Classification ===
Pathohistologically, MASH is graded by the severity of inflammation:

* '''Grade 0:''' Fatty accumulation without inflammation.
* '''Grade 1:''' Fatty accumulation with mild inflammation.
* '''Grade 2:''' Fatty accumulation with moderate inflammation.
* '''Grade 3:''' Fatty accumulation with severe inflammation.

=== 7. Differential Diagnoses ===
Before confirming a MASH diagnosis, clinicians must exclude other conditions that mirror its presentation:

* Alcoholic steatohepatitis (the most significant differential).
* Hepatitis C.
* Autoimmune hepatitis.
* Wilson’s disease.
* Drug-induced hepatotoxicity (e.g., Amiodarone, Methotrexate).
* Other factors: Lipodystrophy, long-term parenteral nutrition, acute fatty liver of pregnancy, or HELLP syndrome.

=== 8. Therapy ===
Treatment is categorized into three primary approaches:

==== Non-pharmacological ====
The cornerstone of MASH treatment is the management of metabolic risk factors, specifically arterial hypertension, type 2 diabetes, dyslipidemia, and obesity. Lifestyle interventions, including consistent physical activity, dietary changes, and a moderate weight reduction of approximately 10%, can lead to the regression of MASH.

==== Pharmacological ====
While several drugs are being studied, the evidence base is evolving:

'''Approved/Established:''' The thyromimetic Resmetirom was approved in the USA in 2024. Per EASL guidelines, Pioglitazone may be considered for MASH patients with type 2 diabetes. While Vitamin E and Pioglitazone have shown potential in reducing steatosis and inflammation in studies, they have not proven effective against fibrosis and are generally not recommended in some guidlines.

'''Ongoing Research (as of 2025):''' Various classes of drugs are currently in trials, including:

* '''GLP-1 Receptor Agonists:''' Liraglutide, Semaglutide, Tirzepatide.
* '''SGLT-2 Inhibitors:''' Dapagliflozin.
* '''Farnesoid-X-Receptor Agonists:''' Tropifexor, GS-9674.
* '''Others:''' Recombinant FGF19 (Aldafermin), Pegylated FGF21 (Pegbelfermin), PPAR-agonists (Elafibranor, IVA337), Chemokine receptor antagonists (Cenicriviroc), ASK1 inhibitors (Selonsertib), Caspase inhibitors (Emricasan), modified bile acids, SSAO inhibitors, and FABAC (Aramchol).

==== Surgical ====
If conventional weight loss methods fail, bariatric surgery may be considered, though it carries significant risks. In end-stage cases, a liver transplant may become necessary.

=== 9. Prognosis ===
The outlook for MASH patients varies. Approximately 10% to 20% of cases progress to higher-grade fibrosis, with fewer than 5% ultimately developing cirrhosis. To assess the risk of disease progression and potential fibrosis, clinicians utilize the NAFLD Fibrosis Score and the FIB-4 Score.

== E. Sources ==
https://my.clevelandclinic.org/health/diseases/15831-fatty-liver-disease

https://flexikon.doccheck.com/de/Hepatitis

https://flexikon.doccheck.com/de/Fettleberhepatitis

https://www.ncbi.nlm.nih.gov/books/NBK526106/

https://www.ucsfhealth.org/care/conditions/toxic-hepatitis

https://my.clevelandclinic.org/health/diseases/17915-toxic-hepatitis

https://www.mayoclinic.org/diseases-conditions/toxic-hepatitis/symptoms-causes/syc-20352202

https://pmc.ncbi.nlm.nih.gov/articles/PMC4836586/

https://my.clevelandclinic.org/health/diseases/15831-fatty-liver-disease

https://www.mayoclinic.org/diseases-conditions/fatty-liver-disease-masld/symptoms-causes/syc-20354567

https://de.wikipedia.org/wiki/Hepatitis

File:HSR.jpg

Arya Pawar — Thu, 30 Apr 2026 13:14:19 GMT

Arya Pawar uploaded File:HSR.jpg

New page

HSR

Celiac disease

Arya Pawar — Thu, 30 Apr 2026 12:44:36 GMT

Complications of untreated celiac disease

@@ Line 70: / Line 70: @@
 The basis of the treatment is a lifelong strict [[gluten-free diet]] - complete exclusion of wheat, rye, barley and oats. Iron Patients should be monitored. As a rule, autoantibody levels are determined once a year. When following a diet, their titer decreases during the first six months. The aim of the dispensary is also the early detection of any related diseases.
-== Complications of untreated celiac disease ==
+== Complications of untreated celiac disease<ref>Robbins Basic Pathology, 10th Ed.</ref> ==
-Untreated celiac disease leads to disorders caused by poor absorption of nutrients and micronutrients, but also to other disorders, the pathogenesis of which is not always clear. Disturbances of somatic development (delayed growth, puberty), osteopathy, anemia and reduced school and work performance are typical. Women suffer from fertility disorders. The risk of psychiatric diseases increases. The incidence of malignancies, especially [[lymphomas]], is also rising significantly.
 == Summary video ==
 [[File:Celiac disease.webm|thumb|center|upright=1.6|Video in English, definition, pathogenesis, symptoms, complications, treatment.]]

Thermoregulation Disorders, Fever, Hyperthermia, Hypothermia, and Therapeutic Hypothermia

User18767 — Thu, 30 Apr 2026 09:58:11 GMT

Created page with " =Thermoregulation Disorders, Fever, Hyperthermia, Hypothermia, and Therapeutic Hypothermia= '''Thermoregulation''' is the physiological process by which the human body maintains a relatively constant core temperature (approximately 36.5–37.5 °C). This regulation is important for optimal enzyme function and metabolic processes. The main control center is the hypothalamus, which combines signals from peripheral and central thermoreceptors and activates appropriate resp..."

New page

=Thermoregulation Disorders, Fever, Hyperthermia, Hypothermia, and Therapeutic Hypothermia=
'''Thermoregulation''' is the physiological process by which the human body maintains a relatively constant core temperature (approximately 36.5–37.5 °C). This regulation is important for optimal enzyme function and metabolic processes. The main control center is the hypothalamus, which combines signals from peripheral and central thermoreceptors and activates appropriate responses.
==Physiology of Thermoregulation==
To maintain a stable temperature, the body manages the balance between generating heat and releasing it
===Heat production===

* basal metabolic processes
* muscle activity (e.g., shivering)
* hormonal effects (thyroxine, [[adrenaline]])

===Heat loss===

* radiation (heat emission to surroundings)
* conduction and convection
* evaporation (sweating)

The [[hypothalamus]] regulates these processes via:

* vasodilation (heat loss)
* [[vasoconstriction]] (heat conservation)
* sweating
* shivering

==Thermoregulation Disorders==
Disorders occur when the regulatory mechanisms fail or are overwhelmed. This could be due to:

* extreme environmental temperatures
* infections
* central nervous system damage
* endocrine or metabolic disorders

The main disorders are fever, hyperthermia, and hypothermia.
==Fever==
When the hypothalamus raises the target temperature, the resulting increase is known as a '''fever'''.
===Pathophysiology===
Fever is triggered by '''pyrogens''':

* exogenous pyrogens (e.g., bacterial toxins)
* endogenous pyrogens (e.g., cytokines such as [[Interleukins|interleukin-1]] and tumor necrosis factor)

These substances stimulate the production of [[prostaglandin E2]] (PGE2) in the hypothalamus, which raises the temperature set point (target temperature of body).
===Phases of fever===

* '''Onset (chill phase)''': vasoconstriction, shivering
* '''Plateau phase''': elevated stable temperature
* '''Defervescence''': sweating and vasodilation

===Function===
Fever enhances immune responses and inhibits pathogen growth, making it a protective mechanism.
==Hyperthermia==
'''Hyperthermia''' is an unregulated rise in body temperature without a change in the hypothalamic set point.
===Pathophysiology===
It is caused by excessive heat production or a failure in cooling mechanisms
===Types===

* '''Heat exhaustion''': dehydration, weakness, sweating
* '''Heat stroke''': severe condition with core temperature > 40 °C, often with central nervous system dysfunction
* '''Malignant hyperthermia''': rare genetic reaction to certain anesthetics

===Characteristics===

* absence of hypothalamic control
* impaired sweating in severe cases
* high risk of organ damage
* Hyperthermia is a medical emergency requiring rapid cooling.

==Hypothermia==
'''Hypothermia''' is defined as a core body temperature below 35 °C.
===Pathophysiology===
It results from excessive heat loss or insufficient heat production.
===Stages===

* '''Mild (32–35 °C)''': shivering, tachycardia, impaired coordination
* '''Moderate (28–32 °C)''': decreased consciousness, slowed metabolism
* '''Severe (<28 °C)''': high risk of ventricular fibrillation and cardiac arrest

===Effects on the body===

* decreased enzyme activity
* slowed nerve conduction
* impaired cardiac function

==Therapeutic Hypothermia==
'''Therapeutic hypothermia''' (targeted temperature management) is a controlled reduction of body temperature to approximately 32–36 °C for medical purposes.
===Indications===

* after cardiac arrest (to improve neurological outcome)
* neonatal hypoxic-ischemic encephalopathy
* traumatic brain injury (in selected cases)

===Mechanism of action===
Lowering temperature leads to:

* reduced metabolic rate (≈ 6–7% per °C decrease)
* decreased oxygen consumption
* reduced production of free radicals
* stabilization of cell membranes
* decreased inflammatory response

===Methods===

* surface cooling (cooling blankets, ice packs)
* intravascular cooling systems
* infusion of cold intravenous fluids

===Complications===

* infections (due to immune suppression)
* electrolyte disturbances (e.g., hypokalemia)
* arrhythmias
* coagulation disorders
* Careful monitoring is required during induction, maintenance, and rewarming phases.

==Summary==
Thermoregulation is essential for maintaining [[homeostasis]]. Fever represents a controlled, beneficial response to infection, while hyperthermia and hypothermia are dangerous conditions resulting from failed regulation. Therapeutic hypothermia is a clinically important intervention that can reduce tissue damage, especially in the brain.
==See also==
[[Homeostasis]]

[[Hypothalamus]]

[[Metabolism]]
==References==
[https://shop.elsevier.com/books/pocket-companion-to-guyton-and-hall-textbook-of-medical-physiology/hall/978-0-443-11102-0 Guyton, A. C.; Hall, J. E.: ''Textbook of Medical Physiology'']

[https://flexikon.doccheck.com/de/Hauptseite DocCheck Flexikon]: ''[https://flexikon.doccheck.com/de/Fieber Fieber]'', ''[https://flexikon.doccheck.com/de/Hyperthermie Hyperthermie]'', ''[https://flexikon.doccheck.com/de/Hypothermie Hypothermie], [https://flexikon.doccheck.com/de/Therapeutische_Hypothermie Therapeutische Hypothermie]''

[https://med.libretexts.org/Bookshelves/Anatomy_and_Physiology/Anatomy_and_Physiology_(Boundless)/5%3A_Integumentary_System/5.4%3A_Functions_of_the_Integumentary_System/5.4B%3A_Thermoregulation LibreTexts Physiology: Thermoregulation]

Binding energy in atomic nucleus

User18767 — Thu, 30 Apr 2026 09:18:32 GMT

Created page with "=Binding energy in the atomic nucleus= '''Binding energy''' is the energy needed to separate an atomic nucleus into its seperate protons and neutrons (nucleons). It is a key concept in nuclear physics, as it explains why nuclei are stable and how energy is released in nuclear reactions. ==Definition== We can define nuclear binding energy as either the energy to disassemble a nucleus or the energy released during assembly. It is calculated using Einstein’s mass–e..."

New page

=Binding energy in the atomic nucleus=
'''Binding energy''' is the energy needed to separate an [[atomic nucleus]] into its seperate protons and neutrons (nucleons). It is a key concept in nuclear physics, as it explains why nuclei are stable and how energy is released in nuclear reactions.
==Definition==
We can define nuclear binding energy as either the energy to disassemble a nucleus or the energy released during assembly.

It is calculated using Einstein’s mass–energy equivalence:

E = Δm · c²

where:

E = binding energy (MeV)

Δm = mass defect

c = speed of light (≈ 3.00 × 10⁸ m/s)
==Mass Defect==
'''Mass defect''' is the difference between:

* the sum of the masses of all protons and neutrons
* the actual mass of the nucleus

It can be calculated using the formula:

Δm = Z · mₚ + N · mₙ − mₙᵤcₗₑᵤₛ

where:

* Δm = mass defect
* Z = number of protons
* N = number of neutrons
* mₚ = mass of a proton
* mₙ = mass of a neutron
* mₙᵤcₗₑᵤₛ = mass of the nucleus

This difference exists because some of the mass is converted into energy when the nucleus forms. This energy is the binding energy.

For example, if you add up the masses of individual nucleons, the result is always slightly larger than the mass of the nucleus. The “missing” mass has been converted into energy that holds the nucleus together.
==Physical Meaning==
Binding energy determines how strongly nucleons are held together by the strong nuclear force. The stronger the binding energy, the more stable the nucleus is.

To compare the different sizes of the nuclei, you can use the '''binding energy per nucleon:'''

Binding energy per nucleon = total binding energy / number of nucleons

This value is useful because it allows comparison between light and heavy nuclei.
==Binding Energy Curve==
When plotting binding energy per nucleon against mass number, a characteristic curve appears:

* it increases quickly for light nuclei
* it reaches a maximum around iron (Fe) and nickel (Ni)
* it slowly decreases for heavier nuclei

This explains two important processes:

'''Nuclear fusion''' (light nuclei combine → energy released)

'''Nuclear fission''' (heavy nuclei split → energy released)

In both cases, energy is released because the products have a higher binding energy per nucleon than the original nuclei.
==Example==
An example is the helium-4 nucleus (²He⁴):

* It consists of 2 protons and 2 neutrons
* The sum of their individual masses is greater than the actual nuclear mass
* The difference corresponds to the binding energy

This is why helium-4 is a very stable nucleus.
==Applications==
Binding energy plays an important role in:

nuclear power plants (fission reactions)

energy production in stars (fusion reactions)

[[radioactive decay]]

[[Nuclear Medicine|nuclear medicine]] and radiation physics
==Summary==
Binding energy is the energy that holds the nucleus together. It comes from the conversion of mass into energy and determines the stability of atomic nuclei. The concept is essential for understanding both natural processes in stars and technological applications such as nuclear energy.
==See also==
[[Atomic nucleus]]
==References==
[https://faculty.kfupm.edu.sa/PHYS/aanaqvi/Introductory-Nuclear-Physics-new-Krane.pdf Krane, K. S. (1987): ''Introductory Nuclear Physics''. Wiley.]

[https://faculty.kfupm.edu.sa/PHYS/aanaqvi/%5BPaul_AP-Tipler-Physics_for_Scientist(BookFi.org).pdf Tipler, P. A.; Mosca, G. (2007): ''Physics for Scientists and Engineers''. W.H. Freeman.]

[https://phys.libretexts.org/Bookshelves/University_Physics/University_Physics_(OpenStax)/University_Physics_III_-_Optics_and_Modern_Physics_(OpenStax)/10%3A__Nuclear_Physics/10.03%3A_Nuclear_Binding_Energy LibreTexts Physics: ''Nuclear Binding Energy''.]

[https://flexikon.doccheck.com/de/Kategorie:Bindungsenergie DocCheck Flexikon: ''Bindungsenergie''.]

Wave properties of particles, quantum properties of waves

Hannasander — Thu, 30 Apr 2026 08:53:13 GMT

← Older revision		Revision as of 10:53, 30 April 2026
(One intermediate revision by the same user not shown)
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	=Introduction=		== Introduction ==
	In classical physics, it was assumed that waves and particles were fundamentally different. Particles were described as stationary objects with mass, whilst waves were considered to be continuous oscillations in both space and time. Modern physics, particularly quantum mechanics, shows that both matter and radiation exhibit dual behaviour. This concept is known as wave-particle duality.<ref>https://www.uni-muenster.de/Physik.AP/Demokritov/en/Forschen/Forschungsschwerpunkte/mBECwiwpd.html</ref>		In classical physics, it was assumed that waves and particles were fundamentally different. Particles were described as stationary objects with mass, whilst waves were considered to be continuous oscillations in both space and time. Modern physics, particularly quantum mechanics, shows that both matter and radiation exhibit dual behaviour. This concept is known as wave-particle duality.<ref>https://www.uni-muenster.de/Physik.AP/Demokritov/en/Forschen/Forschungsschwerpunkte/mBECwiwpd.html</ref>
	==Wave Properties of Particles==		==Wave Properties of Particles==
Line 14:		Line 14:
	*p = momentum		*p = momentum
	This hypothesis states that particles such as electrons can behave like waves under suitable conditions.<ref>https://ethz.ch/content/dam/ethz/special-interest/chab/physical-chemistry/ultrafast-spectroscopy-dam/documents/lectures/allgemeinechemieHS21/Folien/ACPCI_HS21_W10.pdf</ref>		This hypothesis states that particles such as electrons can behave like waves under suitable conditions.<ref>https://ethz.ch/content/dam/ethz/special-interest/chab/physical-chemistry/ultrafast-spectroscopy-dam/documents/lectures/allgemeinechemieHS21/Folien/ACPCI_HS21_W10.pdf</ref>
			[[File:Electron diffraction setup.svg\|thumb\|Electron diffraction ]]

	===Experimental Evidence===		===Experimental Evidence===
	====Electron Diffraction====		====Electron Diffraction====
	The wave nature of electrons was confirmed in the Davisson–Germer experiment, where electrons scattered by a crystal produced an interference pattern.<ref>http://physics.bu.edu/ulab/modern/Electron_Diffraction.pdf</ref>		The wave nature of electrons was confirmed in the Davisson–Germer experiment, where electrons scattered by a crystal produced an interference pattern.<ref>http://physics.bu.edu/ulab/modern/Electron_Diffraction.pdf</ref>
			[[File:Double-slit.svg\|thumb\|Double-slit]]

	====Double-Slit Experiment====		====Double-Slit Experiment====
	In the double-slit experiment, particles such as electrons generate an interference pattern characteristic of waves. This demonstrates that particles behave as probability waves rather than classical objects.<ref>https://uni-tuebingen.de/fakultaeten/mathematisch-naturwissenschaftliche-fakultaet/fachbereiche/physik/institute/astronomie-und-astrophysik/astronomie-hea/forschung/abgeschlossene-projekte/detektorentwicklung/wt-dualismus/</ref>		In the double-slit experiment, particles such as electrons generate an interference pattern characteristic of waves. This demonstrates that particles behave as probability waves rather than classical objects.<ref>https://uni-tuebingen.de/fakultaeten/mathematisch-naturwissenschaftliche-fakultaet/fachbereiche/physik/institute/astronomie-und-astrophysik/astronomie-hea/forschung/abgeschlossene-projekte/detektorentwicklung/wt-dualismus/</ref>
Line 33:		Line 37:
	*ν = frequency		*ν = frequency
	This relation shows that electromagnetic radiation is quantized.<ref>https://www.asc.ohio-state.edu/mathur.16/quantummechanics27-11-17/qm2.2/qm2.2.html</ref>		This relation shows that electromagnetic radiation is quantized.<ref>https://www.asc.ohio-state.edu/mathur.16/quantummechanics27-11-17/qm2.2/qm2.2.html</ref>
			[[File:Photoelectric Effect Schematic-de.svg\|thumb\|Photoelectric Effect]]

	===Photoelectric Effect===		===Photoelectric Effect===
	The photoelectric effect proves that light behaves like particles. Electrons are emitted from a metal surface only when the frequency of the incoming light exceeds a certain threshold.<ref>https://homepage.univie.ac.at/reinhold.bertlmann/pdfs/T2_Skript_Ch_1corr.pdf</ref>		The photoelectric effect proves that light behaves like particles. Electrons are emitted from a metal surface only when the frequency of the incoming light exceeds a certain threshold.<ref>https://homepage.univie.ac.at/reinhold.bertlmann/pdfs/T2_Skript_Ch_1corr.pdf</ref>

Ultrasonography

Hannasander — Thu, 30 Apr 2026 08:46:26 GMT

Created page with "== Definition == Ultrasonography is a noninvasive imaging method that uses high-frequency sound waves to capture real-time images of internal body structures. It is commonly used in diagnostics, monitoring, and interventional procedures.<ref name=":0">https://www.fda.gov/radiation-emitting-products/medical-imaging/ultrasound-imaging</ref> ==Physical Principles== thumb|Piezoelectric effect ultrasound Ultrasonography uses high-f..."

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== Definition ==
Ultrasonography is a noninvasive imaging method that uses high-frequency sound waves to capture real-time images of internal body structures. It is commonly used in diagnostics, monitoring, and interventional procedures.<ref name=":0">https://www.fda.gov/radiation-emitting-products/medical-imaging/ultrasound-imaging</ref>
==Physical Principles==
[[File:Piezoelectric effect ultrasound.gif|thumb|Piezoelectric effect ultrasound]]
Ultrasonography uses high-frequency sound waves (around 2–15 MHz) to look at internal structures for diagnosis. The ultrasound beam is produced by the transducer using the piezoelectric effect, where special crystals convert electrical energy into sound waves and then convert the returning echoes back into electrical signals. These waves travel through the body and get reflected at tissue boundaries. The echoes are used to create the image.

How much gets reflected depends on the difference in acoustic impedance between tissues. If the difference is large, the echos are strong, while similar tissues have only weak reflections. At interfaces like bone or air, almost all sound is reflected, which causes acoustic shadowing. Fluids such as blood or urine don’t reflect much sound, so they appear black (anechoic).<ref>https://radiopaedia.org/articles/physical-principles-of-ultrasound-1</ref><ref>https://vetsuisse.iml.unibe.ch/radiosurfvet/allgemeine-radiologie/ultraschall/grundlagen/piezoelektrischer-effekt-1</ref>
[[File:Ultrasound lesions echogenicity.svg|thumb|330x330px|Ultrasound lesions echogenicity]]

==Image Formation==
*'''Hyperechoic (bright)''' – bone, fibrous tissue, fat
*'''Hypoechoic (dark)''' – soft tissues
*'''Anechoic (black)''' – fluid (e.g., cysts, blood)<ref>https://www.veterinaryradiology.net/4161/what-do-hyperechoic-and-hypoechoic-mean/</ref>
==Modes of Ultrasonography==

=== B-mode ===
The most commonly used mode in ultrasonography is the B-mode (brightness mode), which produces standard two-dimensional images and allows clear visualization of anatomical structures.

=== M-mode ===
The M-mode (motion mode) can evaluate movement, which is particularly useful in cardiology, where it helps assess the motion of the heart walls and valves over time.

=== Doppler effect ===
Most modern ultrasound systems can use the Doppler effect, where the changes in the frequency of ultrasound waves occur when they meet moving objects, to determine the direction and speed of an object in motion. There are different ways to apply the Doppler effect. In general two modes are used to collect Doppler data and two types of visualisation are used to show the Doppler information.

==== Pulsed Wave Doppler (PW) ====
*Emits ultrasound in pulses and measures flow at a specific depth
*Allows precise localization of blood flow
*Limited in measuring high velocities

==== Continuous Wave Doppler (CW) ====
*Continuously emits and receives ultrasound waves
*Accurately measures very high blood flow velocities
*Cannot determine the exact depth of the signal

==== Spectral Doppler ====
*Displays blood flow as a graph (velocity vs. time)
*Provides quantitative and directional information
*Used especially in cardiology (valves, chambers)

==== Colour Doppler ====
*Displays blood flow as colors on the B-mode image
*Shows direction <ref>https://www.imv-imaging.com/en/2023/04/news-the-a-b-ms-ultrasound-modes-explained/</ref>
[[File:A modern medical ultrasound scanner.jpg|thumb|319x319px|modern ultrasound scanner]]

==Equipment==
*Transducer (probe)
*Processing unit
*Monitor
*Ultrasound gel
===Types of transducers===
*'''Linear''' – superficial structures
*'''Convex''' – abdominal imaging
*'''Phased array''' – cardiac imaging
==Clinical Applications==
===Abdominal imaging===
*Liver, gallbladder, spleen, pancreas
*Detection of gallstones, tumors, cysts
[[File:Ultrasonography of sludge and gallstones, annotated.jpg|thumb|385x385px|Ultrasonography of sludge and gallstones, annotated]]

===Obstetrics and gynecology===
*Fetal development monitoring
*Detection of congenital anomalies
===Cardiology (echocardiography)===
*Heart function and valve assessment
===Vascular imaging===
*Detection of thrombosis
*Blood flow assessment
===Musculoskeletal system===
*Tendons, ligaments, joints
===Interventional procedures===
*Guidance for biopsies and drainage<ref name=":0" />
==Advantages==
*Non-invasive
*No ionizing radiation
*Real-time imaging
*Portable and cost-effective <ref name=":1">https://www.euroespa.com/science-education/specialized-sections/espa-pain-committee/us-regional-anaesthesia/ultrasound-pros-and-cons/</ref>
==Limitations==
*Operator-dependent
*Limited in obese patients
*Poor visualization through bone and air
*Lower resolution compared to CT and MRI <ref name=":1" />

== References ==
<references />

Phase Microscopy

Hannasander — Thu, 30 Apr 2026 06:56:05 GMT

Created page with "== Introduction == Phase-contrast microscopy is a specialised contrast-enhancing technique in transmitted light microscopy that makes it possible to visualise transparent specimens that would otherwise remain invisible under normal bright-field microscopy. It is one of the most common and simplest methods for imaging biological specimens and is ideal for visualising living, unstained cells.<ref>https://www.microscopyu.com/techniques/phase-contrast/introduction-to-phase-c..."

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== Introduction ==
Phase-contrast microscopy is a specialised contrast-enhancing technique in transmitted light microscopy that makes it possible to visualise transparent specimens that would otherwise remain invisible under normal bright-field microscopy. It is one of the most common and simplest methods for imaging biological specimens and is ideal for visualising living, unstained cells.<ref>https://www.microscopyu.com/techniques/phase-contrast/introduction-to-phase-contrast-microscopy</ref>

The method was created in 1932 by Frits Zernike (1888–1966) and in 1941 made part of routine microscopic practice by August Köhler and Loos. It quickly transformed research in biology and medicine. For this important discovery, Zernike was awarded the Nobel Prize in Physics in 1953.<ref>https://home.uni-leipzig.de/pwm/web/?section=introduction&page=phasecontrast</ref>

==Physical Principle==
Phase contrast microscopy converts phase differences of light passing through a specimen into visible intensity differences.

When light passes through a transparent specimen, it is phase-shifted due to differences in refractive index and thickness compared to the surrounding medium. These shifts aren’t something the human eye can see directly, so they need to be converted into visible contrast.

This is done using an annular aperture and a phase ring, which change the phase and intensity of the background light. When the light coming from the specimen and the background light recombine, their phase difference is close to 180°, creating interference that makes the structures visible.
[[File:Working principle of phase contrast microscopy.gif|thumb|487x487px|working principle of phase contrast microscopy]]
A typical feature of phase-contrast microscopy is the formation of halo artefacts around structures, which are caused by partial interference of the diffracted light.<ref>https://home.uni-leipzig.de/pwm/web/?section=introduction&page=phasecontrast</ref>
==Optical Components and Mechanism==
===Annular Aperture (Condenser Annulus)===
*Located in the condenser (front focal plane)
*Translucent plate with a circular transparent ring
*Produces a cone of light that illuminates the specimen
===Phase Plate===
*Located in the objective lens (rear focal plane)
*Is often integrated into the objective as a ring
*Selectively adjusts the phase and amplitude of undeviated light
*Shifts the phase of undeviated light by ±λ/4
*Reduces the brightness of background light<ref>[https://www.edmundoptics.com/knowledge-center/application-notes/microscopy/optical-microscopy-application-phase-contrast/#:~:text=Phase%20Plate:%20mounted%20on%20the,a%20defocused%2C%20parallel%20light%20ray. https://www.edmundoptics.com/knowledge-center/application-notes/microscopy/optical-microscopy-application-phase-contrast/#:~:text=Phase%20Plate:%20mounted%20on%20the,a%20defocused%2C%20parallel%20light%20ray.]</ref>
===Mechanism of Contrast Formation===
The light passes through the circular opening and forms a hollow cone that illuminates the specimen. During interaction with the specimen, the light is split into diffracted light, which is phase-shifted by the specimen and undiffracted background light.

The undiffracted light passes through the phase plate, where its phase is shifted and its intensity is reduced. Most of the diffracted light passes around the phase plate and remains unaffected.

Both light components then combine in the image plane, where interference occurs between the diffracted and undiffracted light. This turns small phase differences into visible differences in intensity, creating a contrast.<ref name=":0">https://moticmicroscopes.com/blogs/articles/phase-contrast-by-motic?srsltid=AfmBOop5Lcuvlie8OuMl6g7FF-3k-TGuNYTyJwj52rWuUf0ix0-k04pf</ref>

==Types of Phase Contrast==
===Positive Phase Contrast===
Positive phase contrast is the most frequently used technique in light microscopy. Thicker cellular structures and organelles, such as the nucleus and mitochondria, appear dark against a bright background.
===Negative Phase Contrast===
In negative phase contrast, thicker regions of the specimen appear bright against a dark background. This effect occurs when the direct background light is delayed by a quarter wavelength, resulting in constructive interference.<ref name=":0" />
==Applications of phase contrast microscopy==
===Cell Biology===
*Most common observation without staining of cells in cultures
*Study of cell morphology (structure and shape)
*Observation of cell movement in real time and division processes
*Analysis of cell mortality
===Hematology===
*Examination of living blood cells without staining
*Identification of abnormal cell shapes (e.g., in anemia)
*Observation of platelet aggregation and cell dynamics
===Microbiology and Infectious Diseases===
*Detection of live microorganisms without staining
*Observation of bacterial motility
*Useful for fast early diagnosis of infections<ref name=":1">https://www.bostonind.com/blog/principles-benefits-applications-phase-contrast-microscopy</ref>
==Advantages==
*No staining required (cells remain alive)
*Minimal sample preparation
*Real-time observation
*Enhanced contrast in transparent specimens<ref>[https://www.accu-scope.com/advantages-of-phase-contrast-microscopes-for-clinical-settings/#:~:text=Specimens%20that%20are%20transparent%20or,around%20the%20edges%20of%20particles. https://www.accu-scope.com/advantages-of-phase-contrast-microscopes-for-clinical-settings/#:~:text=Specimens%20that%20are%20transparent%20or,around%20the%20edges%20of%20particles.]</ref>
==Disadvantages==
*Halo artifacts around structures
*Not effective for specimens with low phase difference
*More expensive than a standard light microscope<ref name=":1" />

== References ==
<references />

Macrocytic Anemia

Hamdaan — Thu, 30 Apr 2026 00:40:00 GMT

@@ Line 3: / Line 3: @@
 Those with a high MCV are macrocytic. <ref>MEDICAL PHYSIOLOGY (RHOADES)] Rodney A. Rhoades PhD, David R. Bell - Medical Physiology_ Principles for Clinical Medicine. Chapter 9 Blood components (2012, Lippincott Williams & Wilkins</ref>
-== Causes ==
+== Causes<ref>PAVEL, Klener, et al.  ''Internal Medicine. '' 4th edition. Prague: Galén, 2011. 1174 pp.  [[Speciální:Zdroje knih/978-80-7262-857-5|ISBN 978-80-7262-857-5]] .
 Key Causes:
@@ Line 18: / Line 26: @@
 * GIT – leads to diarrhea.
 * Neurons – demyelination of axons . The principle is the lack of methionine, which is necessary for the synthesis of choline and the phospholipid component of the myelin sheath. In excess, methylmalonyl-CoA occurs, from which defective lipids of the myelin sheath are formed. Typical is the involvement of the posterior and lateral spinal cords, funicular degeneration and peripheral neuropathy . Symptoms include paresthesia , deep sensory disorders , rarely paresis.
-* Homocysteine levels , which are manifested by insufficient conversion of homocysteine to methionine. Homocysteine accumulates and is a risk factor [[Trombóza|for thrombosis]] .[[File:Folicacid-B12.png|thumb|The role of folic acid and vitamin B12 in metabolism]]
+* Homocysteine levels , which are manifested by insufficient conversion of homocysteine to methionine. Homocysteine accumulates and is a risk factor [[Trombóza|for thrombosis]] .