Pathology of nutrition: malnutrition, hyper nutrition, and diabetes

Lecture 5

appropriate diet includes

sufficient energy in the form of carbohydrates, fats, and proteins for body’s daily metabolic needs

essential amino acids and fatty acids for synthesizing structural and functional proteins and lipds

vitamins and minerals for acting as coenzymes or hormones in vital metabolic paths

behaviors/circumstances that lead to malnutrition

poverty, ignorance, alcoholism, acute or chronic illness, self-imposed dietary restriction (anorexia, bulimia)

GI diseases, chronic wasting, acute critical illness

can result in nutrient malabsorption, impaired nutrient utilization or storage, excess nutrient losses, or increases need for nutrients

iron

often develops in infants fed exclusively artificial milk diets

thiamine

when rice is a dietary mainstay

iodine

supplementation is often provided in salt but certain “natural” salt products may lack iodine

common deficiencies

can be remediated by education

protein energy malnutrition

major contributor to death rate for children under 5 in poor countries

marasmus

severe malnutrition

children

weight falls <60% of normal range

with growth retardation, muscle wasting

kwashiorkor

specifically protein deficiency

weight is 60-80% normal but masked by edema

anorexia nervosa

self-induced starvation

marked weight loss

bulimia nervosa

cycles of binging and self-induced vomiting

vitamins

fat soluble: A, D, E, K

water soluble: C, B

vitamin deficiencies

dietary in origin or biological (disturbance in absorption, transport in blood, tissue storage, or metabolic conversion)

do not usually occur in isolation

vitamin a

fat soluble

metabolized from carotenoids which are present in yellow and left green veggies

depleted by infection in kids

toxicity: headache, dizziness, vomiting, bone and joint pain

vitamin a source

animal products

vitamin a storage

liver

vitamin a function

low-light vision, immunity, differential of specialized epithelial cells

vitamin a etiology

poor nutrition, secondary deficiency to conditions that cause malabsorption of fat

vitamin a symptoms

impaired vision, dry eyes, pulmonary infections, immune deficiency

vitamin a toxicity

headache, dizziness, vomiting, bone and joint pain

vitamin d

fat soluble

maintenance of plasma calcium and phosphorus

vitamin d source

solar or artificial UV light, fish, plant

vitamin d function

stimulates intestinal absorption of calcium and phosphorus

collaborates with PTH in mobilization of calcium from bone

stimulates PTH-dependent reabsorption of calcium in renal distal tubules

vitamin d etiology

limited exposure to sunlight, dietary deficiency in calcium or vitamin d, renal disorders

skeletal diseases

rickets: kids

osteomalacia: adults

vitamin c

water soluble

also known as ascorbic acid

vitamin c source

fruits, vegetables, some animal products

vitamin a functions

involved in various biosynthetic paths

scurvy

bone disease in growing children and hemorrhages and healing defects in children and adults

rare but can occur in elderly, chronic alcoholics, or patients undergoing peritoneal dialysis and hemodialysis

obesity

excess body weight sufficient to increase overall morbidity and mortality

BMI

normal range 18.5-25 kg/m2

obesity >30 kg/m2

39.8% of US is obese

skewed for people with muscle mass

importance to healthcare

increases risk of heart disease, stroke, type 2 diabetes, cancer

importance to pharmacists

affects doing weight, volume of distribution, drug deposition in body, half-life

obesity causes

genetic and environmental factors

a lot of convenient, highly palatable, energy-dense, inexpensive foods

differences in extracting energy from food

composition of colonic bacterial communities

lack of exercise, sedentary lifestyle

psychological factors: stress, emotional disturbances

circadian disruption

prior history of obesity

hereditary tendencies

obesity is rarely attributable to a single gene but rare instances of leptin or leptin receptor mutations, POMC path mutations can increase eating

diabetes mellitus

group of syndromes with different etiologies

all result in a failure of glucose homeostasis

failure to maintain blood glucose levels between 70-120 mg/dL

functional deficiency of insulin action

diabetes occurs when your body doesn’t make enough insulin or cannot use the insulin it makes

causes blood sugar to rise to pathological levels

clinical diagnosis of diabetes

random glucose >200 mg/dL with symptoms

fasting glucose >126 mg/dL

oral glucose tolerance test >200 mg/dL over 3-5 hour monitoring

glycated hB >6.5% (reflects average blood glucose levels during previous s2-3 months)

symptoms of diabetes

glucose >150 mg/dL- may be asymptomatic

glucose >200 mg/dL

fatigue

polyuria (inc urine)

polydipsia (inc thirst)

weight loss and muscle wasting (type 1)

ketonemia (type 1, low ketones)

opportunistic infections

type 1 diabetes

complete B-cell destruction and absolute insulin deficiency

5-10% of cases

type 2 diabetes

insulin resistance with insulin deficiency

due to insulin secretory defect with insulin resistance

90-95% of cases

gestational diabetes

second half of pregnancy

increasing hormones that have counter-regulatory anti-insulin effects

9% of population

up to half develop type 2 diabetes for life

type 1

autoimmune destruction of B-cell pool

juvenile diabetes

insulin-dependent

autoantibody-positive

type 1 characteristics

young age of onset and autoantibodies

rapid requirement of insulin to survive

most difficult form for controlling blood glucose levels

polygenic

type 1 symptoms

increased thirst and urination

bed wetting

extreme hunger

weight loss

fatigue, weakness

blurred vision

type 1 etiology

unknown

rates have risen 3-5% globally so maybe environmental factors

identical twins have 27% disease concordance

type 1 treatment

lifestyle changes

insulin

type 2

not associated with significant autoimmunity

insulin resistance

onset >40 years old

no autoantibodies

1/3rd to be insulin dependence

polygenic

variable phenotype

deficiency of insulin action

metabolic syndrome

cluster of features like obesity, large waist circumference, high triglycerides, low HDL, high glucose, high blood pressure

type 2 symptoms

increased thirst and urination

hunger

fatigue

blurred vision

slow healing sores, frequent infection

impaired B-cell function

cells lose sensitivity to glucose or other stimuli

insulin resistance

normal insulin fails to elicit proper clearance of glucose from the blood

hepatic glucose metabolism dysregulation

liver becomes resistant to insulin and undergoes excessive glujconeogeneis and glycogenolysis

hyperglycemia

polyuria, polydipsia, polyphasic

diabetic ketoacidosis

overproduction of ketone bodies from fatty acids

severe hyperglycemia with polyuria with nausea and vomiting to lead to uncompensated fluid loss

can result in coma if extreme

treated with replacing water and electrolytes and giving insulin

microvascular disease

nephropathy, neuropathy, retinopathy

macrovascular disease

coronary artery disease, cerebrovascular disease, peripheral vascular disease, hypertension

associated complications

foot ulcers, infections, skeletal fractures

pathology

high blood sugar destroys neurons and vessels

most easily damaged cells in response to high glucose

vascular endothelial cells, pancreatic B-cells, peripheral neurons

leads to

blindness, leg amputations, kidney failure, peripheral neuropathy, risk for stroke and heart attack

glycemic control

diet, lifestyle, exercise, medication

treat associated conditions

dyslipidemia, hypertension, obesity, CV disease

screen for/manage complications

retinopathy, CV disease, neuropathy, nephropathy, other