pathophysiology group 1 balamiento – balmores – bernardo – cabantac – castellano – chan -...

PATHOPHYSIOLOGY

GROUP 1BALAMIENTO – BALMORES – BERNARDO

– CABANTAC – CASTELLANO – CHAN - CORPUS

PATHOPHYSIOLOGY

• Type II Diabetes Mellitus

• Pneumonia

TYPE II DIABETES MELLITUSPATHOPHYSIOLOGY

• An endocrine metabolic disorder– Primarily involves the pancreatic beta cell


• With symptoms of hyperglycemia– increased peripheral insulin resistance– inadequate pancreatic insulin secretions– Increased hepatic glucose production

• Genetic and environmental factors


• Genetic factors– T2DM among first-degree relatives

• risk by 20 to 40%

– The patient has strong family history• greatly increases the risk of T2DM


• increased peripheral insulin resistance

• inadequate pancreatic insulin secretions

• Increased hepatic glucose production

Increased Peripheral Insulin ResistancePATHOPHYSIOLOGY

• decreased insulin action on peripheral insulin-sensitive tissues

• Initially relative– Hypersecretion of insulin to normalize plasma

glucose levels

Increased Peripheral Insulin ResistancePATHOPHYSIOLOGY

Post-receptor defects FFA

Impaired PI-3-kinase signaling pathway

Impaired translocation of GLUT4

Reduced transport of glucose intracellularly

Elevated FFA levels

Impairs skeletal muscle usageEnhances hepatic glucose

productionImpair beta cell function

Increase hepatic glucose production (unsuppressed gluconeogenesis)

Decreased glucose utilization

Inadequate Pancreatic Insulin Secretions

PATHOPHYSIOLOGYInitially

hyperinsulinemia

Inadequate compensation

progression

Further dec in insulin secretionIncrease hepatic glucose production

Further progression

Beta cell failure

UltimatelyGlucose toxicity

Lipotoxicity

Diabetes

Increased Hepatic Glucose Production PATHOPHYSIOLOGY

Insulin resistance

Failure of gluconeogenesis suppression

Postprandial hyperglycemia

Further reduction in glycogen storage

Symptoms PATHOPHYSIOLOGY

hyperglycemia

Dehydration[decrease skin turgor]

hyperosmolarity

Intracellular water depletion

Trigger osmoreceptors (thirst center)

Polydipsia[increased thirst]


Renal excretion of glucose

Glucosuria[ants around toilet seat]

Exceeds renal threshold for glucose absorption

Increase glucose levels in urine

Promotes osmotic diuresis

Nocturia or polyuria


Eventual decline in insulin levels

Fuel source shifts from carbohydrates to proteins and fats

proteolysis

Usage of gluconeogenic amino acidsDepletion of glycogen stores

Polyphagia

Cells become hungry

Increased appetite to compensate for depleted energy stores


• Obesity– central or visceral obesity is common

• more associated with insulin resistance

– elevated free fatty acids• lipid accumulation (liver and skeletal muscles)

intracellular accumulation of free fatty acid toxic and potently inhibits insulin signaling pathway

– adipokines• adipokine secretion (leptin, adiponectin and

resistin) dysregulation food intake is abnormally increased and subsequent suppression of satiety


• Malaise– decreased glucose (main fuel source)

utilization– Usage of fat as a fuel source

• requires body to use more energy• patient constantly feels weak

Chronic complications PATHOPHYSIOLOGY

• Diabetic retinopathy

• Hypertension stage I

• Infection

DIABETIC RETINOPATHY PATHOPHYSIOLOGY

• nonproliferative diabetic retinopathy– retinal vascular microaneursysms, dot and

blot hemorrhages, and exudates

Several factors Retinal ischemia Neovascularization


• Damaged retinal pericytes– Endothelial supporting cells

• altered retinal blood flow

• Impaired retinal blood flow autoregulation

• Exudation secondary to increased permeability of retinal blood vessels in DM

HYPERTENSION STAGE I PATHOPHYSIOLOGY

Increased sympathetic nervous system activity

hyperinsulinemia

Increased sodium retentionIncreased cardiac output

Increased peripheral vascular resistance

[Landsberg]with anti-natruiretic effects on kidneys

Prevents compensatory mechanism to decrease BP


Vascular smooth muscle hypertrophy

Mitogenic effects of insulin


Modified ion transport

Cell membrane defects

Increased cytosolic calcium levels in insulin-sensitive

tissues

Increased responsiveness to

vasoconstrictor agents

INFECTION PATHOPHYSIOLOGY

• Presence of fever suggests ongoing infection

• Common among diabetic patients– Pneumonia– UTI– Skin and soft tissue infections

Pneumonia PATHOPHYSIOLOGY

• frequent pathogens– Gram-negative organisms, S. aureus and M.

tuberculosis

• Mode of transmission– Aspiration (most likely)– Hematogenous spread– Direct extension


Inhalation of pathogens

Enter the lower respiratory tract

Phagocytosis by alveolar macrophages

[Ljubic et. al.] enhanced adherence of pathogens in

the respiratory epithelium in DM

Impaired intracellular killing

Release of cytokines


• Decreased immune system function– Impaired neutrophil and macrophage

functions • Chemotaxis, adherence, phagocytosis and

intracellular killing

– Intracellular killing• increased glucose levels competes with usage

of NADPH necessary for free radical production decrease levels of free radicals (superoxide and hydrogen peroxide)


Release of cytokines

Local leukocytosisIncreased purulent secretions

Alveolar capillary leakageNarrowing of air passageways

Alveolar hypoxemia

Rales

Stimulation of respiratory centers Tachypnea

Pneumonia PATHOPHYSIOLOGYRelease of cytokines

Circumventricular organs (brain)

Activation of ARA pathway

Production of PGE2Fever

Acts on hypothalamus (ventromedial preoptic area and parvocellular portion of

periventricular nucleus)

Elevation of thermoregulatory set-

point

gen. circulation


• Chest pain.– a reaction to the inflammation– pleuritic chest pain is the usual description

THANK YOU!!!

pathophysiology group 1 balamiento – balmores – bernardo – cabantac – castellano – chan -...

Documents

pathophysiology type

glucose utilization

insulin action

pathophysiology group

polyuria slide

transport of glucose

plasma glucose levels

risk of t2dm slide