Disorders of Fat Soluble Vitamins & Protein Energy Malnutrition


Fat-soluble vitamins

  • The fat-soluble vitamins are vitamins A, D, E, and K; they are stored in fat.

Water-soluble vitamins

  • The water-soluble vitamins are vitamins B and C; being water-soluble, they are NOT stored. The exception is vitamin B12, which is stored in the liver.

Fat malabsorption

  • Fat malabsorption is a key cause of vitamin A, D, E, and K deficiency.
    • Fat malabsorption commonly accompanies celiac disease, cystic fibrosis, pancreatic exocrine insufficiency, biliary obstruction, colitis, and can occur iatrogenically (albeit unintentionally) with laxative abuse via excess mineral oil intake, in particular.
    • Vitamins and minerals serve as coenzymes or hormones in key metabolic pathways, thus we can infer that their disorders lead to metabolic dysregulation of these pathways and dysfunctional assembly of key structural components.
  • Vitamin A (retinol) deficiency most notably causes night blindness.
  • Vitamin D deficiency most notably causes bone anomalies.
  • Vitamin E (tocopherol) deficiency most notably causes anemia.
  • Vitamin K deficiency most notably causes coagulopathy.



  • Indicate that it’s found in leafy vegetables (eg, carrots) meats, and dairy products.
  • It’s found as carotenoids that are metabolized in the body to active vitamin A where its stored in liver cells.

Clinical presentations

  • Indicate that night blindness is a key vitamin A deficiency.
    • To remember this, we draw a set of rod and cone photoreceptors because vitamin A is best known for its role in vision where it’s a key pigment in rods and cones.
  • It prevents the epithelia from undergoing squamous metaplasia – a further differentiation into keratinized epithelium.
  • Indicate that vitamin A deficiency manifests with ocular keratinization: specify the dry eyes (xerophthalmia), which specifically begins with drying of the cornea (xerosis conjunctivae) from keratinization of the lacrimal and mucus-secreting epithelium.
  • Show that, later, the keratin debris builds-up as Bitot spots (small opaque spots), which roughen and destroy the cornea.
  • Next, indicate that keratinization (squamous metaplasia) occurs in the mucus-secreting epithelium of the lungs and kidneys and, as well.
  • Vitamin A also has additional important metabolic effects, especially in fatty acid metabolism.
  • It plays a role in infection control, so indicate that immune deficiency is a consequence of vitamin A deficiency.
    • Thus infectious diarrhea in a newborn can be lethal because it can weaken the host’s immune system when it wastes the newborn’s low supply of vitamin A.


  • Now, consider that vitamin A is used to treat AML: acute promyelocytic leukemia; all-trans retionoic acid induces the ultimate apoptosis of acute promyelocyctic cells.
  • More commonly, it’s used to treat acne but can have significant teratogenicity.

Side Effects

  • Acutely, it causes:
    • GI upset
    • Visual disturbance
  • Chronically it causes:
    • Pseudotumor cerebri, which is a syndrome of pathologic increased intracranial pressure that manifests with headaches and a classic intermittent “rushing” sound.
    • Hepatotoxicity (remember it’s stored in the liver).
    • Alopecia.
    • Arthralgias.



  • Indicate that, for the most part, humans derive vitamin D in the form of vitamin D3 (cholecalciferol).
    • Vitamin D3 is derived from its endogenous synthesis in the skin from its precursor (7-dehydrocholesterol) in a photochemical reaction that involves solar/artificial ultraviolet light.
  • Write that vitamin D2 is the plant form, called ergocalciferol or ergosterol.
  • Indicate that the liver stores vitamin D as 25-OH-Vit. D (vitamin D undergoes 25-hydroxylation in the liver.)
    • Note that we use vitamin D without a subscript, here, because the source (D2 vs D3) is unidentified.
  • Draw a kidney and indicate that it releases 1-alpha hydroxylase, which fully activates vitamin D into 1-25 dihydroxyvitamin D [1,25(OH)2D] (calcitriol): it is the fully biologically activated form.
    • Vitamin D undergoes 1-alpha-hydroxylation in the kidney.
Note that Vitamin D2 is less bioactive than vitamin D3, so you’ll often see vitamin D3 used in reference to biologically active vitamin D.

Causes of vitamin D deficiency

  • Inadequate sunlight exposure
  • Malabsorption
  • Liver failure
  • Renal failure (renal osteodystrophy)

Clinical Presentation

  • Indicate that in children, vitamin D deficiency presents as rickets, which manifests with bowing of the legs and shortening of bones because of its impact during bone growth.
  • In adults it presents as osteomalacia, which manifests with softening of bones.

Vitamin D Toxicity

  • Regarding vitamin D excess, draw an osteoblast and show that vitamin D, along with PTH, is a key stimulus for osteoblast release of RANKL, which promotes osteoclast formation.
  • Thus, vitamin D excess promotes bone loss and excess calcium in the blood and urine, which manifests with stupor and coma.


  • Draw a RBC and indicate that vitamin E is an antioxidant that protects RBCs and membranes from free radical damage.

Clinical Presentations

Hemolytic Anemia

  • Indicate that deficiency of vitamin E manifests with hemolytic anemia.
    Spinocerebellar ataxia
  • Draw a cross-section of a spinal cord.
  • Indicate that vitamin E deficiency may present with spinocerebellar ataxia and most closely resembles Friedreich’s ataxia – so we draw an axial section of Friedreich’s ataxia, now.
  • Vitamin E deficiency presents in late childhood or early teens with symptoms of progressive ataxia and clumsiness, with exam findings of:
    • Large fiber sensory loss
    • Arreflexia with positive Babinski signs
    • Spinocerebellar/cerebellar signs of dysdiadochokinesia and dysarthria
  • Note that vitamin E deficiency is often mistaken for B12 deficiency because of the combination of motor and sensory findings but, importantly, in B12 deficiency there is a megaloblastic anemia with hypersegmented neutrophils and elevated serum methylmalonic acid levels – which are NOT present in vitamin E deficiency.



  • Indicate that vitamin K is derived from the diet (especially green, leafy vegetables) and from bacterial production in the proximal intestine.
  • Draw a liver and small intestine.
  • Show that vitamin K is integral for hepatic synthesis of prothrombin (which is factor II) and factors VII, IX, and X, and also protein C and protein S, which all contain 4-6-gamma-carboxyglutamate residues.
    • Vitamin K (hydroquinone) is necessary for the carboxylation of glutamate residues to form these rare amino acids.

Warfarin & Vitamin K Recycling

  • Indicate that vitamin K hydroquinone is oxidized to vitamin K epoxide via vitamin K epoxidase.
  • Then, show that the epoxide is reduced back to the hydroquinone in two steps vitamin K quinone as an intermediary.
  • Show that warfarin blocks each of these steps: the reduction of the vitamin K epoxide back to vitamin K quinone (via vitamin K epoxide reductase) and also the step back to the hydroquinone (via vitamin K quinone reductase).
    • Thus, warfarin promotes bleeding via inhibition of vitamin K epoxide reduction.
  • If there’s enough vitamin K in the diet, this recycling can be deemed irrelevant and the creation of coagulation factors will continue.
  • On the contrary, if the quantity of vitamin K present in GI tract is insufficient, or it is not properly absorbed and transported to the liver, thrombin production and clot formation will be impaired and bleeding disorders will ensue.

Vitamin K deficiency syndromes:

  • Neonatal hemorrhages occur secondary to sterile intestine and inadequate vitamin K in the breast milk.
    • Vitamin K is present only in very low concentrations in human milk and very little vitamin K actually crosses the placenta from mother to infant, so to prevent vitamin K deficiency in the newborn, intramuscular or oral vitamin K prophylaxis is necessary
    • Newborns are given an injection of vitamin K at birth to prevent vitamin K deficiency.
  • Indicate that prolonged antibiotic-use can also wipe-out intestinal bacteria and cause vitamin K deficiency.
  • Then, indicate that liver failure is a common cause of vitamin K deficiency because the coagulation factors, themselves, are synthesized in the liver, which commonly accompanies a prolonged PT/INR with normal fibrinogen concentration and normal platelet count.
    • In fact, a tip-off of liver failure is an elevated INR in a patient not already on warfarin.


  • Denote that in kwashiorkor there is malnutrition with severe protein depletion.
  • Denote that marasmus refers to malnutrition from generalized calorie deficiency.


  • Indicate that the loss of plasma oncotic pressure leads to peripheral edema, which, to some extent masks the visceral wasting, and is associated with:
    • Protuberant belly
    • Edematous feet
    • Fatty liver from loss of apolipoprotein synthesis
    • “Flaky paint” skin appearance so named because it alternates between hyper- to hypo- pigmentation
    • Shiny skin and alopecia


  • We show a classic picture of a purely wasted thorax from starvation.
  • There’s pure wasting.
  • Growth retardation.
  • Anemia.

Summary Distinction

  • Marasmus patients have an emaciated appearance rather than a swollen appearance because it is typified by a loss of body fat and muscle whereas kwashiorkor results in a loss in plasma oncotic pressure, which produces signs of swelling from edema.

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