Disorders of Cell and Tissue Metabolism

Cellular homeostasis

Cellular homeostasis

cell maintains its morphofunctional integrity

How is cell injury developed?

If the adaptive capability is exceeded or if the external stress is inherently harmful or excessive

if the stress is severe, persistent, or rapid in onset, it results in ___________ ____ ________ and necrosis or apoptosis of cells

irreversible injury

physiologic vs pathologic adaptation

responses of cells to normal stimulation vs to stress

Labile tissue - made by + ex

cells which retained the ability to proliferate in post-natal life and have a high rate of turnover, hematopoietic cells

Stable tissues + ex

good regenerative ability but low rate of turnover, bone

Permanent/differentiated tissues - made by + ex

cells which have lost the ability to proliferate being divided only during fetal life, muscle + neurons

Hyperplasia

enlargement of an organ or tissue due to the increase of cells

During hyperplasia in ________ tissues, the structure of the tissue is not affected

labile

Two types of hyperplasia

compensatory and hormonal

mechanical factors, chronic hypoxia, hormones overproduction, chronic inflammations, tissue repair, genetic factors are all causes of ___________

hyperplasia

Consequences of hyperplasia

malignant transformation (reversible)

Hypertrophy

increase in the size and weight of an organ or tissue due to increase of cells in volume, without division

Hypertrophy is caused either by

increased functional demand or by growth factor or hormonal stimulation

2 types of pathologic hypertrophy

adaptive (after workout) and compensatory

The mechanisms driving cardiac hypertrophy involve at least two types of signals:

mechanical triggers and soluble mediators (for cell growth)

Consequences of hypertrophy

metabolic disorders, sclerosis

Atrophy

decreasing of tissue or organ size by the loss of cell substance

Cellular atrophy results from a combination of decreased _________ _________ and increased __________ ___________

protein synthesis, protein degeneration

Generalized atrophy is associated with

cachexia, malnutrition, senile atrophy

Local atrophy is associated with

decreasing in size, vessels with winding direction

mechanical factors, loss of innervation, malnutrition, hormonal insufficiency, aging are causes of ____--

atrophy

What organs undergo involution/physiological atrophy

thymus + genital organs

Hypoplasia

failure of organ or whole body development, of morphogenesis, decreasing in size

Aplasia

lack of development/morphogenesis of an organ

Agenesis

lack of an organ and its primitive embryological structures

Metaplasia

transformation of a mature tissue into another mature tissue

In which type of cell adaptation does a cell type sensitive to a particular stress is replaced by another cell type better able to withstand the adverse environment?

metaplasia

The influences that induce metaplastic change in an epithelium, if persistent, may predispose to

malignant transformation

Types of metaplasia

squamous (smokers) + columnar (intestinal)

dystrophy

Metabolic disorders with morphological changes

Which disorders are reversible? Dysmetabolism, dystrophy, necrosis

dysmetabolism and partially dystrophy

Hypoxia, physical, infectious + chemical agents, immunological rxns, cell aging, metabolism errors and nutritional imbalances are causes of what?

cell injury

Reversible cell lesions

• Cellular swelling

• Na + /K+ pump

• Steatosis (Fatty change)

• Disorders of ER

Irreversible lesions - apoptosis and necrosis - what happens?

mitochondria + cell membrane fxn loss, cell fragmentation, nucleus necrosis, death

hydroelectrolitic balance disorder

cell hyperhydration due to its inability to regulate the ionic and fluid balance across the plasma membrane

where do hydroelectrolitic balance disorders occur

kidney, liver, myocardium

Parenchymatous (granular) changes of hydroelectrolitic balance disorder

swollen mitochondria, reversible or leads to other metabolic disorders or necrosis

Hydropic or vacuolar degeneration of hydroelectrolitic balance disorder

swollen cytoplasm, reversible process or cell necrosis

Fatty change

accumulation of triglycerides in the cytoplasm of those cells which do not contain them in physiological conditions

Fatty change - unaffected vs affected metabolism

unaffected - fatty infiltration, lipid accumulation caused by hyperlipemia affected - = fatty change caused by hypoxia/anoxia + toxins infections

Morphology of fatty change

enlarged organ, yellow, soft, friable, greasy when cut clear vacuoles in cytoplasms

localization of fatty change in liver

@ lobule periphery - hyperlipemia in center - hypoxia diffuse - toxins

localization of fatty change

liver heart (diffuse) kidney (tubular epithelial cells)

___________ is a simple protein (scleroprotein)

keratin

orthokeratosis

Thickening of stratum corneum without retained nuclei (hyperkeratosis w/o parakeratosis)

Hyperkeratosis

thickening of the stratum corneum

causes of hyperkeratosis

congenital + mech factors, sun, viruses

Parakeratosis

increased epidermal turnover lack of stratum granulosum and lucidum + retention of small nuclei in the stratum corneum pinkish red plaques with fine, silver scales

Dyskeratosis

abnormal keratinization occurring prematurely in the inferior epidermal layers

leukoplasia

mucosal keratinisation, abnormal location of keratinization process

cholesteatoma

abnormal location of keratinization process in tympanic cavity

__________ is a T cell-mediated inflammatory disease

psoriasis

Verrucae are proliferative lesions of _______________ that are caused by ________

squamous epithelial cells HPV

intracell accumulation of proteins causes

nephrotic syndrome, Russel bodies - plasma cells, alcoholic hyaline

bronze diabetes is caused by intracell accumulation of

hemosiderin

lipoidosis is an intracell accumulation of phospholipids and causes

Gaucher, Tay-Sachs disease

glicogenosis (intracell accumulation of glycogen) causes

diabetes, Gierke disease, inflammations (in granulocytes)

Intracellular hyaline deposits occurs where?

1. droplets in renal tubes

2. Mallory bodies, alcoholic hialin (liver)

3. Russel bodies (plasmocytes)

intracell accumulation of cholesterol causes

Cholesterolosis (gallbladder), Xantelasma, Aortic atherosclerotic plaques

Hb pigments w/o iron

bilirubin, porfirin

Hb pigments w/ iron

hemosiderin, hemomelanin (malaria pigment), acid hematin

Non-hemoglobin pigments

melanin, lipofuscin (aging pigment), lipochrom, lutein

exogenous pigments

Pneumoconioses (dust accumulation in lungs), dietary + skin pigmentations

________ is the end product of heme degradation

bilirubin

Localized accumulation of bilirubin occurs within

echymosis (Hb - Biliverdin - Bilirubin) tissues with necrosis

If unconjugated bilirubin levels rise, this unbound fraction may diffuse into ________ and produce toxic injury

tissues

Pathways of bilirubin metabolism

Hb - Biliverdin - Bilirubin-Albumin complex - thru liver - urobilirubin

Jaundice and icterus

yellow-orange coloration of the skin and whites of the eyes caused by high levels of bilirubin in the blood (hyperbilirubinemia)

Mechanic (obstructive or post-hepatic) jaundice - cause

obstruction of the bile ducts

Mechanic (obstructive or post-hepatic) jaundice - consequences

conjugated Bi billiary acids (cholemia) pale faeces (acholia) steatorrhea (fat in stools) lack of Ubg in urine cholangitis billiary hepatitis/cirrhosis

Hepatocellular (intrahepatic) jaundice - cause

lesions of hepatocytes

Hepatocellular (intrahepatic) jaundice - consequences

high levels of alcalin phosphatase + cholesterol decolored faeces (hypocholia) Bi- and Ubg-uria in urine

Hemolytic (pre-hepatic) jaundice - cause

increased hemolysis

Hemolytic (pre-hepatic) jaundice - consequences

hypercolored faeces (hypercholia) in urine: Bi- and Ubg-uria

Morphology of severe jaundice

icterus viridis (green) icterus melas (black)

morpho of jaundice in liver

plugs of Bi in hepatocytes bilirubin cylinders (bile ducts)

morpho of jaundice in kidney

biliary infarction

morpho of jaundice in brain

nuclear jaundice (only in newborns)

Gilbert-Meulengracht syndrome

Congenital disorders of Bilirubin metabolism, reduction of glucuronil-transferase activity fluctuating jaundice, tiredness

Crigler-Najjar syndrome

Congenital disorders of Bilirubin metabolism, lack of glucuronil-transferase, death within first year of life

Dubin-Johnson syndrome

Congenital disorders of Bilirubin metabolism, decreasing excretion of bilirubin, fluctuating jaundice, Bi and pigments within hepatocytes, conjugated Bi, hepatomegaly

Rotor syndrome

Congenital disorder of Bilirubin metabolism, fluctuating jaundice, benign outcome

lipofuscin

• yellow-brown insoluble pigment in lysosomes, 'aging' pigment

lipofuscin accumulates in

hepatocytes myocardium neural cells seminal vesicles

decreased melanin consequences

albinism, vitiligo, leucoderma

Hyperpigmentation (melanin accumulation) consequences

chloasma (pregnancy), Addison disease, Peutz-Jeghers syndrome acanthosis nigricans, xeroderma pigmentosum

Pneumoconioses vs Anthrachosis

Pneumoconioses - dust, occupational lung diseases Anthrachosis - carbon, coal worker's pneumoconiosis

types of melanic tumours

nevi, benign and malignant lentigo, malignant melanoma

Silicosis

disease due to silica or glass dust in the lungs; occurs in mining occupations

Asbestosis

Mg silicate, causes fibrosis and risk for mesothelioma

Congenital metabolic diseases are due to

protein synthesis with defective function

Phenylketonuria (PKU)

Inherited defect of enzymes in the phenylalanine/tyrosine pathway, hyperphenylalaninemia-with impaired brain development (benign is asymptomatic)

Alpha-1-antitrypsin

plasma glycoprotein synthesized by hepatocytes which has an important role in inhibition of proteases, elastase, cathepsin G and proteinase 3 (neutrophils @ inflammation)

lack of alpha-1-antitrypsin - consequences

pulmonary emphysema - loss of alveolar wall elasticity, cause cholestasis - liver cirrhosis

cystic fibrosis - cause

• dysfunction of chloride ion channels in cell membranes

• mutations in the gene CF

• abnormal water and electrolyte transport across cell membranes

cystic fibrosis - symptoms

mucus with abnormally high viscosity in glands lumen, cystic dilatation of glands

cystic fibrosis - localization

pancreas, bronchia, gut, testis

Gierke disease

Glycogen storage disease, in liver + kidney

Pompe's disease

Glycogen storage disease, in heart, liver and muscles