Outline of Lecture
Hyperplasia & Hypertrophy
Cellular Adaptation
After non lethal injury cells may adapt to protect themselves.
Growth
Hyperplasia; Hypertrophy;
Hypoplasia; Atrophy
Metaplasia; Dysplasia.
Degenerations (accumulations).
Hydropic ∆
Fatty ∆
Hyaline ∆
Pigment storage-wear& tear
Adaptation
Reversible cell changes in response to changes in environment & stress ie.
Cell Size———————Hypertrophy
Cell Number————— Hyperplasia
Cell Shape (phenotype) Metaplasia resulting changes in
Metabolic activity
Function of cell.
Adaptation
Hypertrophy
↑ size of cell by ↑ synthesis of structural component resulting ↑ size of organ
↑ functional demand (↑workload for striated muscle )
↑ stimulation by hormones & growth factors. (uterine smooth muscle in pregnancy)
Mechanism of cardiac muscle hypertrophy
Mechanical sensor triggered by ↑ workload.
Growth factors
TGF-β, IGF-1,FGF,α adrenergic agonist, Endo-1,Angt-II.
Phosphoinositide 3-kinase/Akt pathway (exercise, physiologic)
G-protein coupled receptor (pathologic)
Subcellular organelle-myosin fibril
Switching of adult contractile protein to fetal form. (α isoform myosin to β isoform)
Stress beyond the limit of hypertrophy results in regression with loss of myofibrillar contractile protein or cell death .
Hypertrophy of ER
Subcellular organelle
Barbiturate induce hypertrophy of smooth endoplasmic reticulum in hepatocytes.
↑ enzyme cytochrome P-450 mixed function oxidase.
Hypertrophy
↑ cell size by ↑ cell substance
↑ Organ size
Caused by ↑ workload ↑hormone.
Hypertrophy beyond adaptive capacity →degenerative changes & cell/organ failure .
Examples
Skeletal muscle in atheletes
Smooth muscle in gravid uterus
Cardiac muscle in hypertension
Remaining kidney after partial nephrectomy.
Examples of hypertrophy
Muscular hypertrophy
Skeletal muscles in response to strength training (known as muscle hypertrophy). Depending on the type of training, the hypertrophy can occur through increased sarcoplasmic volume or increased contractile proteins.
Ventricular hypertrophy
Ventricular hypertrophy is the increase in size of the ventricles of the heart. Changes can be beneficial or healthy if they occur in response to aerobic or anaerobic exercise, Athletic heart syndrome
but ventricular hypertrophy is generally associated with pathological changes due to high blood pressure or valvular heart disease states.
Congenital /aquired
Hypertrophy of the breasts
Gigantomastia is the extreme growth of the breasts, pregnancy, but also with the more frequently juvenile gigantomastia during puberty (virginal breast hypertrophy).
Hypertrophy of the clitoris
In the most pronounced cases, clitoromegaly is a symptom of intersexuality since the large clitoris resembles a penis (the different grade of genital ambiguity is commonly measured by the Prader classification ranging, in ascending order of masculinisation, from 1: Female external genitalia with clitoromegaly through 5: Pseudo-phallus looking like normal male external genitalia).
Hyperplasia
↑ number of cells in organ / tissue
Physiologic
Hormonal
Compensatory after resection / injury. If one lobe of liver is donated for transplant ,organ grows back to its original size.
Pathologic
Excess hormone in endometrial hyperplasia & prostate hyperplasia
Papilloma virus cause warts
Hyperplasia
↑ number of cells by ↑ rate of division
Cells with mitotic ability can undergo both hyperplasia & hypertrophy
Predisposes to neoplasia.
Mitotic ability of cells
High
epidermis, intestinal epithelium, hepatocytes, BM ,fibroblast
Low
bone, cartilage ,smooth muscles.
Nil
neuron, cardiac muscle ,skeletal muscle.
Types of hyperplasia
Physiologic
Uterine during pregnancy
Female breast during puberty & lactation.
Compensatory hyperplasia in liver
Pathologic
Endometrial hyperplasia ↑ homone
Wound healing
HPV infection
Hyperplasia
(“hypergenesis”) means increase in number of cells/proliferation of cells. It may result in the gross enlargement of an organ .
Hyperplasia is a common preneoplastic response to stimulus.
Microscopically cells resemble normal cells but are increased in numbers
Hyperplasia difference from neoplasia
Hyperplasia is considered to be a physiological (normal) response to a specific stimulus, and the cells of a hyperplastic growth remain subject to normal regulatory control mechanisms
physiological proliferation of cells may in fact be secondarily due to a pathological cause. Still, the proliferation itself is a normal response to another abnormal condition, in contrast to neoplasia, where the proliferation in itself is abnormal.
Hyperplasia Causes
increased demand for example,
proliferation of basal layer of epidermis to compensate skin loss,
chronic inflammatory response,
hormonal dysfunctions, or compensation for damage or disease elsewhere.
growth and multiplication of milk-secreting glandular cells in the breast as a response to pregnancy
induced artificially by injecting hormones such as IGF-1 and human growth hormone
Perhaps the most interesting and potent effect IGF has on the human body is its ability to cause hyperplasia, which is an actual splitting of cells.
Hyperplasia may also occur abnormally, and is associated with a variety of clinical diseases
Some of the more commonly-known clinical forms of hyperplasia, or conditions leading to hyperplasia, are
Benign prostatic hyperplasia, also known as prostate enlargement.
Cushing’s disease – Physiopathology of hyperplasia of adrenal cortex due to increased circulating level of ACTH (adrenocorticotropic hormone).
Congenital adrenal hyperplasia
Endometrial hyperplasia – Hyperproliferation of the endometrium, usually in response to unopposed estrogen stimulation in the setting of polycystic ovary syndrome or exogenous administration of hormones. Atypical endometrial hyperplasia may represent an early neoplastic process which can lead to endometrial adenocarcinoma.
Hyperplasia may also occur abnormally, and is associated with a variety of clinical diseases
Hemihyperplasia when only half (or one side) of the body is affected, sometimes generating limbs of different lengths.
Hyperplasia of the breast – “Hyperplastic” lesions of the breast include usual ductal hyperplasia, a focal expansion of the number of cells in a terminal breast duct, and atypical ductal hyperplasia,
Intimal hyperplasia – The thickening of the Tunica intima of a blood vessel as a complication of a reconstruction procedure or endarterectomy. Intimal hyperplasia is the universal response of a vessel to injury and is an important reason of late bypass graft failure, particularly in vein and synthetic vascular grafts.
Focal epithelial hyperplasia (also known as Heck’s disease) – This is a wart-like growth in the mucous tissues of the mouth or, rarely, throat that is caused by certain sub-types of the human papillomavirus (HPV). Heck’s disease has not been known to cause cancer.
Sebaceous hyperplasia – In this condition, small yellowish growths develop on the skin, usually on the face. This condition is neither contagious nor dangerous.
Compensatory liver hyperplasia – The liver undergoes cellular division after acute injury, resulting in new cells that restore liver function back to baseline. Approximately 75% of the liver can be acutely damaged or resected with seemingly full regeneration through hepatocyte division, i.e., hyperplasia. This is the basis for living-donor liver transplants.
Hypertrophy
(from Greek ὑπέρ “excess” + τροφή “nourishment”) is the increase in the volume of an organ or tissue due to the enlargement of its component cells. It should be distinguished from hyperplasia, in which the cells remain approximately the same size but increase in number. Although hypertrophy and hyperplasia are two distinct processes, they frequently occur together, such as in the case of the hormonally-induced proliferation and enlargement of the cells of the uterus during pregnancy.
