Intracellular vs extracellular activity of antibiotics : PK – PD in action
Dystrophias Intracellular and extracellular accumulation of proteins, lipids and carbohydrates....
-
Upload
lisa-hardy -
Category
Documents
-
view
246 -
download
0
Transcript of Dystrophias Intracellular and extracellular accumulation of proteins, lipids and carbohydrates....
DystrophiasDystrophiasIntracellular and extracellular Intracellular and extracellular
accumulation of proteins, lipids accumulation of proteins, lipids and carbohydrates. and carbohydrates.
Storage diseases. Depositions. Storage diseases. Depositions. Pathology of endogenous Pathology of endogenous
pigments. pigments.
AsAs..prof. Golovata Tatianaprof. Golovata Tatiana
DystrophyDystrophy ( (from the Greek. from the Greek. Dys-disorders and tropho-Dys-disorders and tropho-nutritionnutrition) - a quantitative and ) - a quantitative and qualitative structural changes in qualitative structural changes in the cells and / or intercellular the cells and / or intercellular substance of organs and tissues substance of organs and tissues caused by violation of trophic.caused by violation of trophic.
Morphological essence dystrophyMorphological essence dystrophy
Increase or decrease to-those of any Increase or decrease to-those of any matter contained in the body normallymatter contained in the body normally
Changing the quality, and physical and Changing the quality, and physical and chemical properties of substanceschemical properties of substances
The appearance of ordinary matter in The appearance of ordinary matter in unusual placesunusual places
The appearance and accumulation of new The appearance and accumulation of new substances that are not inherent in the substances that are not inherent in the normal bodynormal body
Causes of abnormal Causes of abnormal accumulation of metabolic accumulation of metabolic
productsproducts 1. Pathology of cells-genetic or 1. Pathology of cells-genetic or
acquired defects of specific enzymes acquired defects of specific enzymes involved in the metabolisminvolved in the metabolism
2. Dysfunction of transport 2. Dysfunction of transport systems (disorders of blood systems (disorders of blood circulation-hypoxia)circulation-hypoxia)
3. Violation endocrine and neural 3. Violation endocrine and neural regulation of trophic.regulation of trophic.
Mechanisms of abnormal Mechanisms of abnormal accumulation of metabolic accumulation of metabolic
productsproducts
InfiltrationInfiltration – ingestion of indigestible – ingestion of indigestible materials and accumulation of exogenous materials and accumulation of exogenous materials in cells.materials in cells.
Mutations causing alterations in protein Mutations causing alterations in protein folding and transport.folding and transport.
PPerverse synthesiserverse synthesis Decomposition - Decomposition - decay lipoprotein decay lipoprotein
complexescomplexes..
Classification of pathological Classification of pathological accumulation of metabolic productsaccumulation of metabolic products
According predominance violation of a particular type of exchange:According predominance violation of a particular type of exchange: a) protein, b) fat, c) hydrocarbons d) mineral For localization of the pathological process:For localization of the pathological process: a) intracellular (parenchymal) b) extracellular (stromal-vascular); c) mixed Depending on the influence of genetic factors:Depending on the influence of genetic factors: a) congenital b) acquired. For prevalence of the process:For prevalence of the process: a) general,a) general, b) local.b) local.
Intracellular Accumulations of Intracellular Accumulations of proteinsproteins
Accumulatios of proteins appear as rounded, Accumulatios of proteins appear as rounded, eosinophilic droplets by denaturation and eosinophilic droplets by denaturation and
coagulation or vacuoles by hydrationcoagulation or vacuoles by hydration
Intracellular Accumulations of Intracellular Accumulations of proteinsproteins
Reabsorption droplets in Reabsorption droplets in proximal renal tubules proximal renal tubules are seen in renal are seen in renal diseases associated diseases associated with protein loss in the with protein loss in the urine.urine.
The process is reversible The process is reversible if the proteinuria if the proteinuria diminishes, the diminishes, the protein droplets are protein droplets are metamolized and metamolized and disappear.disappear.
Pink hyaline droplets Pink hyaline droplets in the renal tubular in the renal tubular epithelium epithelium
Intracellular Accumulations of Intracellular Accumulations of proteins – hydropic swellingproteins – hydropic swelling
Caused hydration Caused hydration of hyaline droplets of hyaline droplets by different toxic by different toxic actionaction
Hydropic vacuolation of Hydropic vacuolation of renal tubular epithelium. renal tubular epithelium. Cytoplasm contains Cytoplasm contains watery vacuoleswatery vacuoles
Intracellular Accumulations of proteins - Intracellular Accumulations of proteins - keratinization disorders keratinization disorders
Keratinization disorders refers Keratinization disorders refers to a large and heterogeneous to a large and heterogeneous group of disorders of group of disorders of cornification, the majority of cornification, the majority of which are genetically which are genetically determined. Actually, the determined. Actually, the ichthyoses constitute the ichthyoses constitute the predominant portion of predominant portion of keratinisation disorders. The keratinisation disorders. The word « ichthyosis » derives word « ichthyosis » derives from the Greek word « from the Greek word « ichthys » which means fish. In ichthys » which means fish. In most cases, the skin most cases, the skin abnormalities appear since abnormalities appear since birth.birth.
Squamous cell carcinoma skin whith Squamous cell carcinoma skin whith keratinizationkeratinization
Keratin pearl (P) or eddy in squamous cell Keratin pearl (P) or eddy in squamous cell carcinomacarcinoma
Extracellular Accumulations of proteins Extracellular Accumulations of proteins – degenerations of connective tissue– degenerations of connective tissue
Mucoid swellingMucoid swelling Fibrinoid swellingFibrinoid swelling HyalinosisHyalinosis
Extracellular Accumulations of proteins Extracellular Accumulations of proteins – degenerations of connective tissue– degenerations of connective tissue
Mucoid swellingMucoid swelling is a stromal is a stromal dysproteinosis with superficial dysproteinosis with superficial disorganization of protein in connective disorganization of protein in connective tissues with accumulation of basic tissues with accumulation of basic substance glycoaminoglycan and their substance glycoaminoglycan and their redistribution which cause the increasing redistribution which cause the increasing of vessels permeabilityof vessels permeability
MucoidMucoid
Occasionally connective Occasionally connective tissue appears to secret tissue appears to secret mucinmucin
Characterised by Characterised by metachromasiametachromasia
Fibrinoid swellingFibrinoid swelling
It is a stromal It is a stromal vascular dystrophy vascular dystrophy defined by destruction defined by destruction of collagen fibers and of collagen fibers and basic substances with basic substances with plasmorrhagia and plasmorrhagia and formation of protein formation of protein and polysaccharide and polysaccharide complexes on complexes on fibrinoid fibrinoid substancesubstance
HyalineHyaline
It is a stromal vascular dysproteinosis It is a stromal vascular dysproteinosis defineddefined by alteration in the extracellular by alteration in the extracellular space whichspace which becomes homogenous, becomes homogenous, glgloossy, pink ssy, pink aappearanceppearance in sectionin sections s stained with haematoxylin and eosinstained with haematoxylin and eosin
HyalineHyaline
The term “hyaline” The term “hyaline” is used in many is used in many situations where situations where degeneration is not degeneration is not a feature, e.g. a feature, e.g. glossy capsule of glossy capsule of spleen, dense spleen, dense cartilage likecartilage like valve valve
Intracellular accumulation of Intracellular accumulation of lipids – fatty changelipids – fatty change
This is accumulation of fat in non-fatty This is accumulation of fat in non-fatty tissues, especially the parenchymatous tissues, especially the parenchymatous organs, skeletal muscles and the heart, organs, skeletal muscles and the heart, which have a high metabolic rate. which have a high metabolic rate.
Fatty changeFatty change
Development mechanism:Development mechanism:
Causative factorCausative factor: cell poisons : cell poisons (bacterial, chemical e.g. alcohol) and (bacterial, chemical e.g. alcohol) and clinical disorders (anaemia, cardiac clinical disorders (anaemia, cardiac failure, diabetes mellitus) failure, diabetes mellitus) →→ ReducedReduced cellular enzyme activity → cellular enzyme activity → InabilityInability to to metabolise fat metabolise fat →→ AccumulationAccumulation of fat in of fat in cellscells
Fatty changeFatty changeIn normal non-fatty tissues the In normal non-fatty tissues the
intracellular fat is not visible intracellular fat is not visible by light microscopy using by light microscopy using conventional fat stains.conventional fat stains.
In fatty change, the In fatty change, the accumulated fat is visualised accumulated fat is visualised using frozen sections, using frozen sections, stained by Sudan III and stained by Sudan III and indicated by bright orange indicated by bright orange vacuoles vacuoles
In routine paraffin sections the In routine paraffin sections the fat has been dissolved and is fat has been dissolved and is indicated by clear vacuoles indicated by clear vacuoles
Fatty changeFatty change
For exampleFor example Fatty liver – organ is Fatty liver – organ is
enlargement and enlargement and yellow – “yellow – “goose goose liverliver””
A heart on the inside of A heart on the inside of which stripes of which stripes of yellowish or white, yellowish or white, tiger skin is simulated tiger skin is simulated – “– “tiger hearttiger heart”. ”.
Effect of fatty Effect of fatty myocardium is cardiac myocardium is cardiac failure failure
ObesityObesity
Obesity is defined as a Obesity is defined as a body mass index equal to body mass index equal to or greater than 30or greater than 30..
The main cause of oThe main cause of obesity besity isis increased intake of increased intake of food.food.
Manifestations:Manifestations:
increased of adipose tissue increased of adipose tissue in the fat depotsin the fat depots
ObesityObesity
Obesity must be Obesity must be distinguished from distinguished from intra-cellular fatty intra-cellular fatty change describe above. change describe above. Gross degrees of obesity Gross degrees of obesity lead to increased lead to increased adipose tissue in adipose tissue in abnormal sites, e.g. abnormal sites, e.g. between myocardial between myocardial fibres.fibres.
Metabolic disturbances of Metabolic disturbances of cholesterolcholesterol
Accumulation of cholesterol manifested Accumulation of cholesterol manifested histologically by intra-cellular vacuoles, are seen histologically by intra-cellular vacuoles, are seen in several pathologic processes, e.g. in several pathologic processes, e.g. atherosclerosis, xanthomas.atherosclerosis, xanthomas.
STORAGE DISEASES - STORAGE DISEASES - INBORN ERRORS OF INBORN ERRORS OF METABOLISMMETABOLISM
Inborn errors of metabolism are Inborn errors of metabolism are single-gene defectssingle-gene defects resulting in resulting in the absence or deficiency of an enzyme or the synthesis of a the absence or deficiency of an enzyme or the synthesis of a
defective protein.defective protein.
Inborn errors of metabolism have four possible Inborn errors of metabolism have four possible consequences:consequences:
accumulation of an intermediate metabolite (e.g. homogentisic accumulation of an intermediate metabolite (e.g. homogentisic acid in alkaptonuria) acid in alkaptonuria)
deficiency of the ultimate product of metabolism (e.g. melanin deficiency of the ultimate product of metabolism (e.g. melanin in albinos) in albinos)
synthesis of an abnormal and less effective end product (e.g. synthesis of an abnormal and less effective end product (e.g. haemoglobin S in sickle cell anaemia) haemoglobin S in sickle cell anaemia)
failure of transport of the abnormal synthesised product (e.g. failure of transport of the abnormal synthesised product (e.g. α1-antitrypsin deficiency). α1-antitrypsin deficiency).
Disorders of carbohydrate metabolismDisorders of carbohydrate metabolism The commonest disorder The commonest disorder
of carbohydrate of carbohydrate metabolism with an metabolism with an inherited component in inherited component in its aetiology is diabetes its aetiology is diabetes mellitusmellitus. .
HHistological manifestationsistological manifestations:: reduce glycogen content in reduce glycogen content in
traditional depot, e.g. in the traditional depot, e.g. in the liverliver
accumulation in abnormal accumulation in abnormal places, e.g. in the renal places, e.g. in the renal tubular epithelium tubular epithelium
TISSUE DEPOSITIONSTISSUE DEPOSITIONS - Amyloid - Amyloid
In this condition, a 'waxy' substance composed essentially of an abnormal protein is deposited in the extracellular tissues, particularly around the supporting fibres of blood vessels and basement membranes. Amyloid is resistant to degradation and removal by the usual process so that the deposition progresses relentlessly.
DetectionDetectionof of AmyloidAmyloid
Amyloidosis of the kidney. Amyloidosis of the kidney. sections stainedsections stained Congo Red Congo Red
Amyloidosis of the adrenal. Amyloidosis of the adrenal. sections stainedsections stained Congo Red Congo Red
CLASSIFICATIOCLASSIFICATIONNof Amiloidosisof Amiloidosis
Pathological effects Pathological effects
Calcification - Abnormal deposits of calcium salts Calcification - Abnormal deposits of calcium salts occur in two circumstances: occur in two circumstances: dystrophicdystrophic and and
metastaticmetastatic.. DystrophicDystrophic calcification occurs calcification occurs
in tissue already affected by in tissue already affected by diseasedisease.. Common examples Common examples are: are:
atheromatous plaques atheromatous plaques calcification of mitral valve calcification of mitral valve
ring ring old tuberculous lesions old tuberculous lesions fat necrosisfat necrosis old thrombiold thrombi necrotic tissuenecrotic tissue dead parasitesdead parasites
CalcificationCalcification
Metastatic Metastatic calcification is much calcification is much less common than less common than dystrophic calcification dystrophic calcification and occurs as a result and occurs as a result of hypercalcaemia. of hypercalcaemia. Frequent causes are: Frequent causes are:
hyperparathyroidism hyperparathyroidism
Pathology of endogenous pigments. Pathology of endogenous pigments.
Melanin pigmentationMelanin pigmentation Local melanin pLocal melanin pigmentationigmentation
This is seen in tumor derived from This is seen in tumor derived from the melanocytes of the skin the melanocytes of the skin and choroid cost of the eyeand choroid cost of the eye
Pathology of endogenous pigments. Pathology of endogenous pigments.
MelaninMelanin pigmentation pigmentation GeneralisedGeneralised melanin melanin
pigmentation (melanosis) pigmentation (melanosis) is ais a characteristic of this characteristic of this condition which involves the condition which involves the destruction of the adrenals, destruction of the adrenals, adrenal thus remuving the adrenal thus remuving the inhibitory adrenal control.inhibitory adrenal control.
Pigmentation is seen on Pigmentation is seen on exposed skin surfaces, and exposed skin surfaces, and those subject to local those subject to local irritation including squamous irritation including squamous mucous surfaces such as the mucous surfaces such as the mouth.mouth.
Pathology of endogenous pigments.Pathology of endogenous pigments.Iron-containing pigment - Iron-containing pigment - haemosiderinhaemosiderin
It is iron derived from red cells It is iron derived from red cells breakdown is held in the spleen, liver and breakdown is held in the spleen, liver and marrow. When the amount of iron within marrow. When the amount of iron within the cells becomes excessive and overloads the cells becomes excessive and overloads the ferritin system, it is deposited in a the ferritin system, it is deposited in a brown granular form – brown granular form – haemosiderinhaemosiderin. .
This occurs in two situations:This occurs in two situations:1.1. Local breakdown of red cells in tissues Local breakdown of red cells in tissues
e.g. in internal haemorrhage.e.g. in internal haemorrhage.2.2. Visceral siderosis – this is seen in the Visceral siderosis – this is seen in the
liver, spleen in cases of haemolytic liver, spleen in cases of haemolytic anaemia, and in blood transfusion. Iron is anaemia, and in blood transfusion. Iron is found in the liver parenchyma. Easily found in the liver parenchyma. Easily demonstrated by the Prussian Blue demonstrated by the Prussian Blue reaction.reaction.
Pathology of endogenous pigments.Pathology of endogenous pigments.LipofuscinLipofuscin
This is yellowish brown This is yellowish brown pigment having a high pigment having a high lipid content, often lipid content, often found in the atrophied found in the atrophied cells of old age – “wear cells of old age – “wear and tear” pigment. It is and tear” pigment. It is particularly common in particularly common in the heart muscle around the heart muscle around nucleus.nucleus.
Pathology of endogenous pigments.Pathology of endogenous pigments.
Iron-free pigment - Iron-free pigment - BilirubinBilirubin
When the bilirubin content When the bilirubin content of the serum rises above 34 of the serum rises above 34 μμmolmol//l, jaundice appears. l, jaundice appears. This can be brought about by This can be brought about by an abnormality in one of an abnormality in one of main ways:main ways:
1.1. Post - hepatic (obstructive) Post - hepatic (obstructive) jaundicejaundice
2.2. Pre- hepatic jaundicePre- hepatic jaundice
3.3. Hepato-cellular jaundiceHepato-cellular jaundice
Thank you for your attentionThank you for your attention